INTRODUCTION

With the development of affordable, high-resolution, real-time ultrasound equipment, and the
introduction of transvaginal scanning, the indications for pelvic imaging have increased dramatically.
The gynecologist/ultrasonographer now has the capability of visualizing processes in vivo that, only a
few years ago, could only be inferred. The appropriate integration of real-time ultrasonography into the
practice of gynecology is a subject of continuing controversy.1,2,3,4,5,6 Questions regarding its cost-
effectiveness and diagnostic utilization have been raised.7 Other authors support the modality as a
means of obtaining a better understanding of gynecologic pathology as well as enhancing the
diagnostic ability of the practicing gynecologist.8,9,10
As health-care reimbursement evolves into a managed care mechanism, it is necessary to
reevaluate management protocols to ensure maximum value. Traditional approaches to the evaluation
of common gynecologic abnormalities, such as abnormal uterine bleeding or asymptomatic ovarian
cysts, have to be reassessed.
In selected cases, expectant follow-up with anticipated spontaneous resolution of the process
is preferable to relatively costly surgical management. With this in mind, the modern gynecologist must
consider the existing scientific evidence regarding the diagnostic accuracy, advantages, disadvantages,
and pitfalls of gynecologic ultrasonographic imaging. It is imperative that we explore this modality
thoroughly and consider how it can be integrated into our daily practice to improve patient care in a
cost-effective manner.
The practitioner is, therefore, confronted with several important decisions regarding pelvic
ultrasonography, including whether or not to become actively involved as a gynecologic
ultrasonographer, whether or not to refer patients for consultative ultrasonography, and most important,
which patients should be evaluated with real-time ultrasonography in the optimum care setting. As we
look toward the twenty-first century, the clinical settings in which two-dimensional pelvic imaging and,
more recently, Doppler imaging of the pelvis are used, will continue to expand as we strive to gain a
more accurate assessment of the anatomic and functional status of the female pelvis.
Gynecologic processes of interest that are now approachable with ultrasonographic imaging
include localization and characterization of pelvic masses; assessment and evaluation of early
pregnancy location and potential viability; screening for and assessment of adnexal masses; monitoring
of follicular development; a more in-depth assessment of the difficult-to-examine patient; and
evaluation of pelvic blood velocity waveforms by Doppler imaging. All of these areas are discussed in
this chapter.

Principles of ultrasonographic imaging

For optimum ultrasonographic visualization, certain mechanical, physical, and
ultrasonographic principles must be understood. The quality of an image ultimately depends on the
degree of resolution. In general, the closer the transducer tip is to the imaging target, the greater the
resolution, and therefore the clearer the image will be. Every effort must be made to avoid interference
with transmission of ultrasonographic energy.11 A thorough understanding of the longitudinal
(sagittal), cross-sectional (axial), and coronal anatomy of the pelvis is necessary for optimal image
interpretation. Whereas scanning planes for transabdominal scanning are classically described as
sagittal, axial, and oblique, the transvaginal approach offers the additional coronal scanning plane.12,13
Accurate orientation is a necessity for the appropriate interpretation of pelvic imaging. Since much of
the imaging is performed with the use of "organ specific" planes, one must always be aware of the
actual scanning orientation in order to achieve an accurate interpretation of the findings noted on the
image.13
In addition to the need for close approximation of the imaging target by the transducer, one
must also realize that the quality of the image will be influenced by the frequency of the transducer,
pulse repetition frequency, and image processing. For a more in-depth analysis of these imaging
principles, the reader is referred to standard texts on ultrasonography.

1
Doppler Ultrasonographic Scanning
The direction, velocity, and variability of blood flow can be evaluated ultrasonographically by
using the principle of the Doppler effect. By displaying the Doppler frequency shifts that result from
calculating the difference between the emitted frequency and the frequency of echoes returning from a
moving target, a flow velocity waveform is created. This can be described in terms of velocity (in
centimeters per second), as well as by using descriptive ratios depicting the difference in the systolic
velocity and diastolic velocity.
The S/D ratio (also referred to in some literature as the A/B ratio) is calculated by dividing the
systolic maximum velocity by the diastolic minimum velocity. As the diastolic velocity approaches
zero, however, this relationship becomes less accurate. To avoid this problem, other ratios are also
used. The pulsatility index is calculated by dividing the difference between the systolic and diastolic
velocities by the mean velocity ([S - D]/mean velocity). The resistance index divides the same
numerator by the systolic velocity.
The velocity of blood flow is influenced by myocardial contractile force, vessel diameter, and
downstream resistance. The interpretation of flow velocity waveforms requires a realization that blood
flow velocity and volume of flow are not synonymous because of the effect of vasoconstriction.
As is addressed later, the ability to visualize small arteries with color Doppler interrogation
offers the potential for further evaluation of the physiology and pathophysiology that may occur in the
female genital tract. When ordering and/or interpreting Doppler studies of the ovary and/or uterus, one
must always be cognizant of the effect of estrogen and progesterone on the blood flow velocity
waveform. In general, during the periovulatory and luteal phases, there is an increasing diastolic
velocity (reduced S/D ratio, pulsatility index, or resistance index). This realization is necessary for the
correct interpretation of blood flow velocity waveforms in the premenopausal patient. Keeping these
principles in mind, one can see the potential improvement in diagnostic accuracy in the assessment of
functional, as well as pathologic, conditions in the gynecologic patient.14,15,16

Scanning techniques
At the present time there are two basic scanning approaches applicable to gynecologic
ultrasound imaging: transabdominal and transvaginal. The transabdominal technique refers to
insonation of the pelvis through a partially distended urinary bladder to minimize the acoustic
impedance of interposed bowel gas. This scanning technique may be performed with static scanning or
real-time equipment offering sagittal, axial, and oblique planes of pelvic anatomy for evaluation.
Static scanners produce repetitive still images of pelvic anatomy. Echoes that return from
multiple acoustic interfaces are detected by a manually maneuvered transducer and are electronically
combined to produce the final display. Real-time scanners differ from static scanners in that the image
approximates actual motion. The image is created by displaying multiple returning images at a very
rapid frame rate to reflect the actual activity that is happening.22
The evaluation of blood flow depends on the imaging of a flow velocity waveform depicting
an upstroke (systolic) velocity generated by myocardial systole and interval velocity, which is a
function of downstream resistance. The vessels to be insonated can readily be delineated by color
Doppler and studied by specific vessel insonation to establish the Doppler waveform mentioned above
(Fig. 13).
The transvaginal technique, which uses a transducer inserted into the vagina, has emerged as a
separate scanning technique applicable to gynecologic ultrasonography.23 Sagittal, coronal, and
oblique images of the pelvic viscera may be obtained, as demonstrated in Figure 14 and Figure 15.
Transvaginal ultrasonography offers a number of advantages over transabdominal ultrasonography.
First, the scanning tip may be placed closer to the scanning target, thus enhancing resolution. Second, a
full urinary bladder is not needed, resulting in a procedure that is much more acceptable to most
patients. Third, transvaginal ultrasonography interfaces nicely with the pelvic examination, which can
be performed at the same sitting. Fourth, the image quality of transvaginal ultrasonography has been
found superior to transabdominal ultrasonography in most instances, although the depth of penetration

2
is comparatively limited. Finally, the transvaginal approach offers superior tissue characterization of
the uterus and ovaries.24
A complete ultrasonographic evaluation of the pelvis, however, should include transabdominal
ultrasonography if any question exists regarding the possibility of pedunculated masses, ovarian cysts
that may be on long pedicles, or other masses that may not be readily visible by the vaginal route.
Similarly, a postvoid transabdominal scan may allow visualization of previously unapparent masses.25
With either technique, it is imperative that the ultrasonographer employ a deliberate scanning
technique that allows interpretation of echoes in an organized and thorough manner, paying constant
attention to orientation. The entire pelvis should be explored with documentation of the appearance of
the adnexa, uterus, cervix, and any other significant pelvic structures that are noted. Although Doppler
insonation is feasible with either technique, most favor the transvaginal Doppler approach because of
its ability to approximate the pelvic vasculature.

Minimizing artifacts
Artifactitious echoes may produce confusing images. Procedures that will minimize artifacts
include avoiding interspersed air between the scanning tip and the imaging target, appropriate
sensitivity setting of the scanning instrument, use of variable bladder distention, and careful integration
of ultrasonographic images with knowledge of the expected pelvic anatomy. Nonetheless, the
ultrasonographer should always realize the potential for a certain echo to be artifactitious in nature. The
realization of this possibility minimizes the likelihood that an artifact will be interpreted as a significant
pathologic process. A repeat study after bowel evacuation may be helpful.

3
 DIAGNOSTIC ULTRASONOGRAPHY IN
GYNECOLOGY
Utilization of real-time ultrasonography by the gynecologist
Real-time ultrasonography, and more specifically, intravaginal or transvaginal real-time
ultrasonography, interfaces well with the pelvic examination and offers the potential for enhanced
diagnostic accuracy of gynecologic conditions. As noted above, the knowledge of sagittal, coronal, and
axial anatomy; attention to maximizing image detail; and correlation with the patient's history and
physical examination should offer a comprehensive evaluation of the gynecologic patient. In all
probability, the role of gynecologic scanning will continue to expand. The correlation of palpable
pelvic findings with visual images of tissue texture should enhance the diagnostic acumen of the
clinical gynecologist. It is incumbent on all clinicians, however, to continue to strive to delineate the
appropriate utilization of this modality and to limit its use to those clinical situations when the cost-
benefit ratio clearly warrants its use.
In closing, a word should be mentioned regarding training and experience of the gynecologic
ultrasonographer. At this time, no specific guidelines exist regarding the educational experience
necessary for assurance of competence in gynecologic imaging. Prerequisites to the utilization of this
technique are a thorough knowledge of gynecologic physiology and pathology; the ability to access or
obtain a thorough gynecologic history and physical examination; and experience in acquisition, display,
and documentation of ultrasonographic images. Obviously, attention to continuing education through
periodicals and postgraduate courses is necessary if the physician is to stay abreast of this rapidly
expanding field.

Normal pelvic anatomy

UTERUS

Regardless of the scanning approach used, a reliable landmark for orientation is the uterus
(Fig. 1). For this reason, it is more difficult to scan posthysterectomy patients than those with a uterus
in situ. The uterus should be readily seen in the midplane of the pelvis and normally exhibits an echo
density that is clearly distinguishable from surrounding pelvic viscera (Fig. 2). The endometrial echo
has a variable density, depending on water content and cellular density, that fluctuates with the
hormonal status of the patient (Fig. 3). The changes noted in endometrial ultrasonographic appearance
have been characterized. Progressive echogenicity of the functional zone (compactum and spongiosum)
occurs with completion of the preovulatory phase and during the secretory phase.17 The thickness of
the endometrium correlates with the histologic response to estrogenic stimulation.18 The relative
position of the uterus to the cervix and to the axis of the vagina should be noted. Retrodisplacement of
the uterus usually produces a less clearly defined image on transabdominal scanners, but does not
interfere with uterine delineation significantly using the transvaginal approach.19 The shape or
symmetry of the uterus should also be assessed during the scanning session.

CERVIX. The uterine cervix is visible and may be measured with a great degree of accuracy,
especially with the transvaginal technique. It should be remembered that with the transvaginal
approach, the cervix may not be seen if the scanning tip is placed in either the anterior or posterior
fornix. For this reason, careful scanning during insertion and removal of the scanning transducer is
advisable.

4
URINARY BLADDER

The urinary bladder is usually very clearly seen and represents another landmark for anatomic
orientation in transvaginal and transabdominal scanning. The bladder should be partially distended
before attempting transabdominal scanning. Caution must be used to differentiate a full urinary bladder
from a unilocular, anechoic-type ovarian cyst that may lie anterior to the uterus. If any question
regarding this possibility exists, a postvoid scan is advisable for definitive evaluation.
Excessive filling of the urinary bladder displaces the uterus so posteriorly that not only does
the patient experience undue discomfort, but adequate imaging is difficult. Conversely, in the
interpretation of transabdominal images with inadequate bladder filling, significant posterior uterine
wall or fundal pathology may be missed. The appropriate amount of urine in the bladder for optimal
visualization varies from patient to patient.
During insonation of unilocular cystic structures, a proximal artifact may occur as a result of
near-field sensitivity, or of the "gain setting" producing near-field reverberation artifact. To the
uninitiated, this echo may appear to represent intracystic echo-dense areas. Variation of the sensitivity
(gain setting) of the equipment allows these areas to be differentiated from more significant findings.
On either side of the urinary bladder in the anterolateral pelvic area are the iliopsoas muscles.
These areas should not be confused with pathologic pelvic masses (Fig. 4).
Frequently the urethra and the urethrovesical junction can be visualized. Transvaginal or
perineal (introital) scanning will enhance this imaging of these structures.

VAGINA

The vagina appears as a collapsed tubular structure lying inferior to the urinary bladder and
distal to the uterine cervix by transabdominal scanning. Transvaginal ultrasonography does not
delineate the vagina as well as the transabdominal or perineal (introital) approach. Anomalies of
vaginal development are discussed later in this text.
Occasionally, with overdistention of the urinary bladder, urine may accumulate in the vagina
(Fig. 5). Likewise, the presence of tampons or menstrual blood may be discerned.

ADNEXA

The adnexa include the ovaries, fallopian tubes, blood vessels, supporting ligaments, and
peritoneal folds of the lateral pelvis. The main structures that are recognizable with ultrasonography
include the ovary, fallopian tube, and vascular anatomy.

OVARY. The position of the ovary is somewhat variable, depending on the length of the
infundibulopelvic ligament, the presence or absence of adhesions, and other anatomic abnormalities
that may displace the ovary. Usually, the ovaries lie in a lateral position to the uterus and are
identifiable by scanning in transverse or longitudinal planes lateral to the uterine corpus. Identification
of the internal iliac vessels with transvaginal ultrasonography is helpful in identifying the appropriate
location of the ovary, but manipulation of the scanning transducer to bring out the full extent of the
ovarian echo is frequently necessary. During transvaginal scanning, the manipulation should be
performed slowly, and patient cooperation is helpful. In the absence of pelvic adhesive disease, the
ovary is noted to move in response to transducer manipulation.
With the availability of high-resolution ultrasonography, the ability to monitor follicular
development exists. Follicles are clearly visible in the majority of ovaries in women of reproductive
age, and appear as echo-sparse, well-circumscribed areas within the ovarian stroma, varying between 5
and 20 mm in diameter (Fig. 6). Ultrasonographic follicular monitoring has become an integral aspect
of ovulation induction protocols by allowing correlation of serum estradiol levels with follicular
diameter during gonadotropin stimulation. A follicular diameter of 18 to 22 mm is characteristic of a
periovulatory follicle.20,21

5
 Ovarian blood supply is largely from the ovarian artery coursing through the
infundibulopelvic ligament. Velocity waveform analysis reveals increasing diastolic velocity in the
periovulatory and luteal phase (Fig. 7 and Fig. 8).

FALLOPIAN TUBE. The fallopian tube is difficult to visualize in the normal state. Frequently,
in cases of abnormal tubal morphology, such as after the development of a hydrosalpinx or neoplasm,
the tube may be more clearly defined. Transvaginal ultrasonography results in a higher frequency of
tubal visualization. A hydrosalpinx is typically a convoluted, anechoic tubular structure (Fig. 9).
Frequently the tube and ovary form a complex, echo-dense, adnexal mass in cases of adhesive
inflammatory disease of the pelvis or a neoplastic process.

OTHER PELVIC FINDINGS

TRUE AND FALSE LIGAMENTS OF THE UTERUS. The supporting uterine ligaments are
rarely clearly visualized with ultrasonography. The folds of peritoneum covering the vascular and
lymphatic supply to the ovary and uterus (infundibulopelvic and broad ligaments) are not true
ligaments and are not seen; the uterosacral ligaments are also not usually seen. The round ligament,
which is actually a tubular structure composed of smooth muscle, may be seen. Variable echo densities
and reflected echoes may result from inflamed peritoneal surfaces involved in adhesive pelvic disease.
In most instances, however, the echo pattern is such that, although a more echo-dense peritoneal area
may be visualized, a definitive diagnosis is usually not possible.

BOWEL CHARACTERISTICS. The presence of gas and feces in the bowel produces a
variably dense echo return. Peristalsis is easily seen. Frequently, gas-filled bowel will have proximal
echoes with poor distal echoes due to gas attenuation of the ultrasound energy. Occasionally, a
distended loop of bowel may be confused with a complex cystic or solid adnexal mass. The possibility
of a primary bowel process must always be considered in the diagnosis of adnexal processes.

URETERS. The ureters are rarely visualized with ultrasonography unless they are specifically
searched for and somewhat dilated. In transverse section, the ureter may be seen juxtaposed near the
lateral border of the uterine cervix. Most ureteral imaging via either the transabdominal or transvaginal
route is done in situations where there is a concern regarding a potential ureteral dilatation, as in
patients with parametrial extension of cervical carcinoma.

PELVIC VASCULAR ANATOMY. The internal iliac vessels, as previously noted, serve as
landmarks for ovarian location (Fig. 10). The uterine arteries may be visualized occasionally and are
frequently noted to exhibit prominent pulsations in early pregnancy. Pelvic vessels that are amenable to
insonation for Doppler study include the ovarian and uterine arteries, as well as vascular structures
within the stroma of pelvic masses.

CUL-DE-SAC FLUID ACCUMULATION. The presence of fluid in the cul-de-sac is a

frequent finding. Small amounts of peritoneal fluid will accumulate in the inferiormost portion of the
cul-de-sac as a result of the menstrual cycle. Massive accumulations of fluid may exist in cases of
ovarian carcinoma (Fig. 11). The hemoperitoneum of ruptured tubal pregnancy is very apparent during
transabdominal or transvaginal scanning (Fig. 12).

Characterization of pelvic masses

Ultrasonographically detected masses should be classified as predominantly cystic or solid.
Cystic masses produce anechoic or hypoechoic images with excellent through-transmission of sound
resulting in a bright, distal surface (acoustic enhancement). Solid masses attenuate the sound energy
and result in poor penetration. Masses containing gas also demonstrate poor sound transmission, with
clear proximal borders and indistinct distal boundaries.26 Cystic masses containing blood, tissue

6
fragments, or other material are described as complex because they produce a cystic appearance as
judged by sonic transmission, but the echo density of the intracystic material is greater than that of fluid
alone.27 This type of echo pattern is frequently referred to as low-level echo density.
In addition to ultrasound characteristics, masses should be categorized by the suspected site of
origin or location (e.g., uterine, ovarian, adnexal, cul-de-sac). If the site of origin is unclear, then a
statement delineating separate, noninvolved organs is frequently helpful (e.g., an adnexal mass that
does not appear to arise from either ovary).
The size of pelvic masses is usually measured along specified scanning planes in order to
allow volume assessment if desired. In addition, the character of a cyst wall (smooth versus irregular)
and intracystic anatomic appearance (e.g., septated, papillary) also assists in establishing the likelihood
of a neoplastic or reactive (inflammatory or endometriotic) process, as opposed to a functional process.

Gynecologic abnormalities

CONGENITAL ABNORMALITIES

MÜLLERIAN (PARAMESONEPHRIC). Müllerian anomalies of the reproductive tract may be

divided into two broad categories:

1.Patients with a normal 46,XX karyotype who exhibit abnormalities of the reproductive tract
secondary to partial or complete failure of müllerian development or fusion.
2.Patients with abnormal karyotypes, including lack of an X chromosome (45,X), presence of a
Y chromosome or portion of a Y, or a mosaic combination of these karyotypes.

Patients with Normal Chromosomes. Anomalous development in patients with a normal 46,XX
karyotype usually involves failure of canalization of the developing müllerian tubercle as it meets the
invaginating urogenital sinus or incomplete fusion of the paired müllerian ducts. Anomalies resulting
from abnormal müllerian tubercle fusion with the urogenital sinus and canalization include imperforate
hymen and transverse vaginal septum. During attempted transvaginal scanning, a hematocolpos may be
noted as cystic dilatation of the superior vagina with cephalad displacement of the uterus and other
pelvic viscera (Fig. 16 and Fig. 17).28,29,30,31,32,33,34 Ultrasonographic guidance may offer
intraoperative assistance in correcting these anomalies.35
Patients with failure of müllerian differentiation to the degree where there is no discernible
uterus or cervix and only small fibromuscular condensations of tissue near the gonad may represent the
Mayer-Rokitansky-Küster-Hauser syndrome (müllerian agenesis).36 Ultrasound evaluation of these
patients reveals no apparent uterus, but gonadal development is noted in the adnexal areas.33
Abnormalities of müllerian fusion in chromosomally normal 46,XX patients may result in a
variety of uterine abnormalities, ranging from a true bicornuate uterus to uterine septation.37,38,39,40
The presence of two distinct endometrial cavities is discernible by ultrasonography; however, some
difficulty may be encountered in establishing whether or not a septate or bicornuate uterus exists (Fig.
18). The association of müllerian anomalies with renal anomalies must always be kept in mind.

Patients with Abnormal Chromosomes. Patients with androgen insensitivity syndrome, who
manifest a 46,XY karyotype, exhibit no uterine development and have intraabdominal testes. The
shallowness of the vagina in these patients, along with sparse pubic hair, chromosomal constitution,
and serum androgen concentration, are helpful in the differential diagnosis of this syndrome and
müllerian agenesis. Gonads containing a Y chromosomal component or a portion of a Y chromosome
should be removed because of the risk of gonadoblastoma development in the gonad.41
Patients with 45 X gonadal dysgenesis will reveal a sexually infantile body habitus as well as
a prepubertal uterine morphology (Fig. 19).42 Monitoring of the change in uterine morphology
secondary to estrogen replacement therapy reveals a transformation of the uterus into a more adult-type
appearance with fundal dominance (Fig. 20).

7
 In summary, transabdominal and transvaginal ultrasonography are excellent additions to the
pelvic examination in patients suspected of anomalous reproductive tract development. The
transperineal technique may be beneficial in the peripubertal patient who is difficult to examine and
who has signs and symptoms of possible cryptomenorrhea.37

WOLFFIAN (MESONEPHRIC). Nonanomalous embryologic remnants of the wolffian ducts

may occasionally be seen. Epoophoron cysts or hydatids of Morgagni produce small anechoic areas
adjacent to the ovary. Gartner's duct cysts are located in the anterolateral areas of the vagina and are
also anechoic and unilocular (Fig. 21). These structures are of minimal clinical significance and rarely
warrant any significant management.

OTHER ABNORMALITIES OF DEVELOPMENT. Uterine and cervical abnormalities due to

in utero exposure to diethylstilbestrol have been documented. The depiction of this abnormality by
ultrasonography has not been as clear as with hysterosalpingography.43

GYNECOLOGIC CONDITIONS OF THE UTERUS

MYOMETRIUM. Leiomyoma. Uterine enlargement not due to pregnancy is most often due to
uterine leiomyomata. Uterine leiomyomata represent proliferations of smooth muscle and are benign
neoplasms. Leiomyomata are classified by their location as subserous, intramural, or submucous.
Ultrasonographically, leiomyomata exhibit poor sound transmission because much of the sonic energy
is attenuated by the solid consistency of the mass. Uterine contour irregularity is one of the most
consistent findings44; however, a variety of findings may occur.45 Ultrasonography offers the potential
of measuring uterine leiomyomata in those patients in whom a conservative or nonsurgical
management plan is initiated (Fig. 22 and Fig. 23).46 In addition, ultrasonography may detect early
signs of degeneration or calcification of uterine leiomyomata. The effect of gonadotropin-releasing
hormone suppression of uterine leiomyomata is easily monitored by ultrasonography. Occasionally,
leiomyomata may undergo degeneration and mimic other cystic pelvic masses.47,48

Leiomyosarcoma. Rarely, a malignant leiomyosarcoma may be found. Leiomyosarcomas

present a complex echo pattern somewhat analogous to uterine leiomyomata with degeneration.
Differential diagnosis of these clinical phenomena requires more extensive analysis. Two-dimensional
imaging is rarely diagnostic of this process, but evidence of increased diastolic velocity with Doppler
ultrasound may assist in the diagnosis.49

ENDOMETRIUM. The endometrium is clearly imaged with pelvic ultrasonography, especially

the transvaginal technique. Endometrial thickness correlates well with the endometrial response to
estrogen stimulation. Morcos and associates50 noted that an endometrial echo greater than 1.5 cm had
a sensitivity of 94% and specificity of 93% in predicting a withdrawal bleeding response to
progesterone in amenorrheic reproductive-age women.
The instillation of a small quantity of sterile saline into the endometrial cavity
(hydrosonography) creates an ultrasonographic interface between solid tissue and liquid. This results in
improved visualization of the endometrium in general, and the endometrial surface in particular. This
procedure has also been termed hysterosonography or sonohysterography.
A small polyethylene catheter or pediatric Foley catheter is inserted through the cervix into the
endometrial cavity after appropriate cleansing with an antiseptic solution. Concurrent real-time imaging
via the transvaginal or transabdominal technique allows visualization of the separation of the
endometrial surfaces as the fluid is instilled (Fig. 24, Fig. 25, and Fig. 26).
Using this technique, the ultrasonographer can achieve better delineation of endometrial
polyps, submucous leiomyomata, and the configuration of the endometrial cavity. There is a potential
for this technique to enhance the endometrial assessment of patients on tamoxifen therapy as well.
Using this technique to evaluate small endoluminal masses within the endometrium, Dubinsky
and colleagues51 detected 19 endoluminal masses in 48 patients with an endometrial thickness of 5 to
10 mm. These masses were clearly diagnosed as either endometrial polyps or submucous leiomyomata.

8
 Concurrent transabdominal scanning and transcervical instillation of saline is another
technique used to visualize the endometrial anatomy. Cicinelli and co-workers52 reported a sensitivity
of 100% in the diagnosis of submucous leiomyomata with this technique. An excellent description of a
variety of hydrosonograpic findings was reported by Goldstein.53
Transvaginal ultrasonography offers the opportunity to visualize the endometrium (Fig. 27 and
Fig. 28). In an effort to select patients at an increased risk of endometrial pathology, several authors
have evaluated the reliability of inferring endometrial histology from measuring the width of the
endometrial echo (Fig. 29).
Granberg and associates54 evaluated 205 women with postmenopausal bleeding and noted
benign endometrial histology with an endometrial width (thickness) of less than 9 mm. The mean
endometrial width in patients with endometrial cancer was 18.2 ± 6.2 mm compared to 3.4 ± 1.2 mm in
those with atrophic histology. Malpani and co-workers55 reviewed endometrial thickness
measurements in patients with endometrial hyperplasia compared to those with normal histopathology.
The mean width of the endometrial echo in patients with hyperplasia was 18.8 mm compared to 5.4
mm in the benign group. Varner and colleagues56 also noted benign findings in patients with an
endometrial thickness of less than 5 mm.
In an effort to compare the diagnostic accuracy of transvaginal ultrasonography, endometrial
cytology, and histologic assessment of specimens obtained via dilatation and curettage, Karlsson and
associates57 performed all three of these techniques on 105 patients with postmenopausal bleeding.
The sensitivity and specificity of these three modalities were essentially the same (sensitivity 81%,
specificity 58%), leading these authors to conclude that the method of transvaginal scanning and
endometrial thickness measurement was a "valuable adjunct" in managing these patients.
Realizing that false-positives and -negatives exist for virtually all testing schemes, it must be
emphasized that the patient's response to therapy and persistence of concerning symptoms must be
addressed with more in-depth study. To emphasize this point, a study from Norway by Dorum and co-
workers58 noted that 3 of 54 patients with endometrial carcinoma had an endometrial thickness of less
than 5 mm. Two patients had stage 1 adenocarcinoma of the endometrium; the third had endometrial
involvement by a malignant lymphoma.
It appears that the likelihood of a malignancy in a patient with a thin endometrium, negative
endometrial biopsy, or normal specimen obtained via dilatation and curettage is very low. Persistent
bleeding, failure of expected response to therapy, development of new symptoms, or persistence of
concerning symptoms require further evaluation. It appears, therefore, that a postmenopausal patient
with a very thin (less than 5 mm) endometrial width may be managed without endometrial sampling or
curettage for abnormal bleeding, assuming an appropriate response to therapy follows.59
The value of ultrasound assessment of endometrial carcinoma, particularly the depth of
invasion of the myometrium, is under investigation. Endometrial carcinoma produces an irregularity of
the endometrial cavity in advanced cases (Fig. 30).60,61,62,63 Of 25 cases of endometrial carcinoma,
the correct depth of invasion was predicted in 21.64 In a separate study, Conte and associates65
confirmed these data, predicting the correct amount of myometrial invasion in 18 of 20 patients.
The finding of endometrial fluid should heighten the ultrasonographer's suspicion of
unapparent abnormalities of the genital tract. Of 17 postmenopausal patients with endometrial fluid
collection, 5 had malignancies: 2 had ovarian cancer, 1 had tubal carcinoma, 1 had endometrial
carcinoma, and 1 had cervical carcinoma.66

CERVIX. In addition to visualization of the volume of cervical cancer,67 the evaluation of

parametrial involvement has also been performed (Fig. 31). Using a transrectal probe, Yamamoto and
Kitao68 evaluated the accuracy of ultrasonographic prediction of parametrial involvement compared
with computed tomography and Federation of International Gynecology and Obstetrics (FIGO) staging
and noted a sensitivity of 83% and specificity of 97%. The potential also exists to assess Doppler flow
characteristics of the uterine arteries in cervical malignancy.

Gynecologic conditions of the adnexa

9
FUNCTIONAL OVARIAN PROCESSES

FOLLICULAR MATURATION. As noted earlier, in addition to the delineation of specific

ovarian masses, follicular maturation may be monitored by serial transabdominal or transvaginal
ultrasonography.69 Preovulatory follicular development is clearly seen with progression of follicle
diameter to the 18 to 22 mm range at midcycle. Follicular dominance and progression are easily
monitored by real-time ultrasonography in correlation with serum estradiol concentration in efforts to
induce ovulatory ovarian function (Fig. 32 and Fig. 33).70,71,72,73,74,75 Transvaginal-directed oocyte
retrieval for assisted reproductive techniques is now the preferred method of acquiring oocytes.

POLYCYSTIC OVARY SYNDROME. Polycystic ovary syndrome produces a wide spectrum of

menstrual disturbances and manifestations of androgen excess. The ovary also may exhibit a variety of
appearances, ranging from multiple cystic follicles (2.5 cm) of varying sizes to only a few follicle cysts
(>2.5 cm) (Fig. 34).76,77,78,79,80,81,82 In cases of hyperthecosis, in which fewer follicles are
developed, the ovary would be expected to exhibit a more solid echo pattern. Monitoring of the
changes in ovarian volume with suppressive treatment with gonadotropin-releasing hormone analogs
has been described.83

OVARIAN MASSES. The ovary has the capacity of developing many different cystic and solid
masses. Transvaginal and transabdominal ultrasonography can categorize adnexal masses into various
echo densities and morphologies, thereby narrowing the differential diagnosis. The reliability of
ovarian size assessment has been documented to be high, with a correlation coefficient of 0.960
between observers documented by Higgins and co-workers.84

Ovarian Cysts. Unilocular cystic masses with few intracystic echoes are most likely serous-type
cysts of the ovary (cystic follicles or follicle cysts) or serous cystadenomas (Fig. 35). Cystic masses
with complex echogenic intracystic echoes are more commonly hemorrhagic in origin (hemorrhagic
corpus luteum cysts or endometriomata).85
A more conservative management approach is feasible in patients with reassuring intracystic
morphology (e.g., anechoic, smooth wall, no papillary excrescences). The decreased need for surgery in
children was demonstrated retrospectively in 1989 by Thind and colleagues,86 who reviewed the cases
of 64 children with ovarian cysts. In addition, the potential also exists for therapeutic cyst aspiration
using ultrasound guidance of selected cysts in young women.87,88 In patients for whom expectant
management is elected, comparative studies after subsequent cycles or hormonal therapy is feasible,
especially with the transvaginal technique.
The differentiation between endometriomas and nonendometriotic ovarian cysts was
investigated by Guerriero and associates,89 who evaluated 251 premenopausal, nonpregnant patients
using transvaginal ultrasound. Of the 31 diagnosed as ovarian endometriomas, 24 were confirmed as
endometriomas by histologic assessment. The sensitivity of transvaginal ultrasound in differentiating
endometriotic cysts from cysts of other etiologies was 83% and the specificity 89%. The authors noted
that this was compatible with the diagnostic accuracy of magnetic resonance imaging.
Controversy exists regarding the significance of cystic masses in the postmenopausal age
group. Fleischer and associates90 published an excellent correlation of ultrasonographic findings with
subsequent histopathology of 67 ovaries in 37 postmenopausal patients. A positive predictive value of
92% and a negative predictive value of 92% were noted in this highly selected population. Luxman and
colleagues91 noted that 2 of 29 ovarian cancers were not detected by transabdominal ultrasonography.
Goldstein and co-workers92 and Andolf and Jorgensen93 noted no malignancies in hypoechoic cysts
less than 5 cm in more than 190 patients.
Therefore it appears that small, nonsuspicious cystic areas in postmenopausal patients may be
followed conservatively with surgical evaluation for persistent cysts or those that progressively
increase in size. The absolute maximum cystic diameter that may be followed safely is debatable, but
appears to be in the 3.5 to 5 cm range. If a noninterventional posture is selected, the ultrasonographer
must realize that a small likelihood of an unapparent malignancy exists and that close follow-up is
mandatory.

10
 Ovarian Neoplasms. Germ Cell Tumors. The most common neoplasms of reproductive-age
women are germ cell tumors. Cystic teratomas are well-circumscribed, complex, cystic masses that are
usually unilateral and exhibit a variably complex, intracystic echo pattern (Fig. 36 and Fig.
37).94,95,96 This type of tissue characterization is important because these complex cystic masses
require surgical evaluation for definitive therapy more often than the smaller, unilocular, serous-type
cysts, which may be followed expectantly. Rupture of cystic teratomas during pregnancy is a major
complication that should be avoided.97 Although the specific pathologic diagnosis of an ovarian mass
cannot be made ultrasonographically, ultrasound can be used to categorize and describe these masses in
order to establish a more precise differential diagnosis.98

Stromal Neoplasms. Solid ovarian neoplasms include those arising from ovarian stromal cells
(fibroma and thecoma)99 (Fig. 38) and the Brenner cell tumor.100

Ovarian Carcinoma (Epithelial Ovarian Tumors). Ovarian malignant neoplasms produce a

variety of ultrasonographic patterns that typically produce an image of mixed solid and cystic
components, irregular septations, and coexistent ascites, and they are frequently bilateral (Fig. 39 and
Fig. 40).101,102
The role of ultrasonography in screening for ovarian cancer is controversial. An ever-
increasing body of literature continues to question the costeffectiveness of ultrasound as a screening
modality. A thorough review of this controversy is beyond the scope of this chapter. Suffice it to say
that as of this writing, ultrasound screening for ovarian cancer is by no means widely accepted. The
combined use of tumor-associated antigens (e.g., CA-125) with ovarian imaging by two-dimensional
technique and Doppler may offer an enhanced potential for diagnosis of ovarian malignancies in high-
risk groups.14,103,104
The salient question that must be answered before recommending universal ovarian cancer
screening with this modality encompasses the reliability and cost-effectiveness of the screening
protocol to detect early (stage I or stage II) disease. The realization that CA-125 levels are not elevated
in many cases of early-stage disease raises a serious question regarding the efficacy of this serum test
as a screening component. The question of routine ovarian cancer screening remains unanswered. The
role of ultrasonography in staging and follow-up of ovarian cancer continues to expand. Conte and co-
workers105 described the potential value of ultrasound study in the preoperative staging of ovarian
carcinoma. Although ultrasonography can detect macroscopic residual disease with acceptable
accuracy, its limitation in detecting small residual disease in lieu of second-look laparotomy has been
demonstrated by Murolo and associates.106
Breast cancer and gastrointestinal tract cancer may metastasize to the ovary. Other ovarian
neoplasms have been described ultrasonographically, including Brenner and Krukenberg
tumors.107,108 The Krukenberg tumor has been characterized ultrasonographically as a complex solid
mass and a cystic mass, but is unlike the ultrasound picture of primary ovarian carcinoma.109 Ovarian
neoplasms may be imaged more precisely by the vaginal approach. Figure 41 shows the image quality
of an ovarian thecoma by transvaginal ultrasonography.
Many articles have been published further describing the ultrasonographic two-dimensional
image characteristics of ovarian cancer. In addition, Doppler interrogation of small vessels detected by
color Doppler imaging reveals increased diastolic flow velocities and evidence of neovascularization
secondary to tumor angiogenesis. The resultant calculations of waveform flow velocity ratios are
therefore decreased.
Multiple scoring systems for two-dimensional findings and two-dimensional and Doppler
findings have also been created. The details of these systems are beyond the scope of this chapter.
Suffice it to say that the various scoring systems offer the potential of assigning numeric values to the
well-known findings of ovarian malignancy, such as thickened cyst walls, septations, papillary
excrescences, complex intratumoral echoes, and disorganized echo texture. The addition of Doppler
waveform analysis frequently confirms the concern of nonreassuring two-dimensional findings, but
rarely increases concern in patients with benign-appearing cysts on two-dimensional findings.
Brown and co-workers110 evaluated 44 masses with two-dimensional and color Doppler
imaging. They noted significant overlap in the resistance index and pulsatility index between benign
and malignant masses. This finding contrasts with that of other investigators.111

11
 FALLOPIAN TUBE CARCINOMA. Although much less common than ovarian carcinoma,
cancer of the fallopian tube exhibits a similar clinical course. The complex echo pattern of tubal
carcinoma diagnosed by transvaginal ultrasonography has been described.112,113,114

PELVIC INFLAMMATORY DISEASE AND ENDOMETRIOSIS

Other adnexal processes exclusive of neoplastic changes include pelvic inflammatory disease
and endometriosis. Pelvic inflammatory disease most often results from a primary salpingo-oophoritis
that has progressed to some degree of hydrosalpinx formation with adhesive pelvic disease. A variety of
ultrasonographic findings with differing types of complex adnexal masses result with frequent
visualization of tubal dilatation and intrafallopian tube fluid (hydrosalpinx formation).115 The ability
to diagnose and guide aspiration of tubo-ovarian abscesses with transvaginal ultrasonography has been
documented.116,117,118,119,120
It is frequently extremely difficult to establish the precise etiology of complex adnexal masses
on an endometriotic or inflammatory basis.121,122,123 Endometriosis will also produce complex
adnexal masses with distortion of the pelvic anatomy typical of adhesive disease (Fig. 42, Fig. 43, Fig.
44, and Fig. 45). In some instances, endometriotic involvement of a nongynecologic structure, such as
the urinary bladder or liver, has been noted.124,125,126

INTRAUTERINE DEVICES

Ultrasonographic localization of intrauterine devices (IUDs) has been possible for many years
(Fig. 46). The advent of transvaginal scanning increases the accuracy of IUD localization.127 IUD
removal under transabdominal ultrasound guidance offers a more precise and potentially less traumatic
removal in difficult clinical settings.128,129 The ability to extract an IUD that is juxtaposed, but
inferior to, an early intrauterine pregnancy is also occasionally enhanced by transabdominal ultrasound
guidance.

EARLY PREGNANCY

INTRAUTERINE PREGNANCY. The most common cause of uterine enlargement is early

pregnancy. The advent of transvaginal ultrasonography offers the capability of extremely early
diagnosis of pregnancy. The prominent echogenicity of decidualized endometrium is clearly seen on
transabdominal or transvaginal scanning before the visualization of a gestational sac.130,131 With
currently available transvaginal imaging techniques, a gestational sac that is located within the uterine
cavity and developing normally should be clearly visible, concomitant with a serum human chorionic
gonadotropin (hCG) concentration of 1000 mIU/mL (Second International Standard [2nd IS]).132
Using the transabdominal technique, the same author reported the discriminatory zone to be 1800
mIU/mL (2nd IS).133 It should be noted that the First International Preparation (1st IRP) standard
results in hCG values that are approximately twice the 2nd IS values. Other published analyses of
transvaginal ultrasound have shown lower discriminatory zones of 300 mIU/mL (2nd IS),134 450 to
750 mIU/mL (presumed 2nd IS),135 and 1100 mIU/mL (1st IRP).136 From a clinical standpoint, if a
quantitative hCG exceeds 1000 mIU/mL and an intrauterine gestational sac cannot be seen with
transvaginal scanning, the suspicion of an ectopic pregnancy must increase, and serial follow-up or
further evaluation is indicated. Studies of serial scanning of patients conceiving during in vitro
fertilization cycles reveal the presence of a gestational sac at even lower hCG concentrations.137
The correlation of gestational sac visualization and serum hCG concentration offers the
practicing gynecologist a powerful tool for early diagnosis of extrauterine pregnancy. The principles of
management, evaluation, and diagnosis presuppose knowledge of the rate of increase of hCG
concentration in normal pregnancy and correlation with ultrasonographic findings. As a general rule,
hCG should double every 2 to 3 days during the early first trimester.138,139,140,141 Many ectopic
pregnancies exhibit a subnormal rise in hCG.

12
 Early intrauterine pregnancy scanning displays the developing amniotic membrane, chorion,
and yolk sac.130,142 Before visualization of the fetal pole, the assessment of pregnancy status depends
on the rate of growth of the sac and correlation with hCG levels. Early in gestation the mean sac growth
is 0.9 to 1.13 mm/day.136 A yolk sac should be seen when the mean sac diameter exceeds 2 cm, and a
fetal pole should be visible after the sac exceeds 2.5 cm (Fig. 47)143 using the transabdominal
approach. Transvaginal scanning allows visualization of the embryo with a mean sac diameter of 1.2
cm.144 As the first trimester progresses, the fetus can easily be outlined, and the cephalic pole, caudal
pole, limb buds, and umbilical cord can be delineated.135 The presence of fetal cardiac activity in early
pregnancy scanning indicates an excellent prognosis for the pregnancy. Fetal cardiac flicker can be
seen in embryos of at least 5 mm with transvaginal scanning and in embryos of at least 9 mm with the
transabdominal approach.144 In published series, the likelihood of spontaneous abortion of
ultrasonographically normal pregnancies in the 8- to 12-week range approximates 2% to 4%.145
Before cardiac flicker becomes apparent, correlation of the gestational sac size with quantitative hCG
assessment provides important predictive information. If the hCG concentration is clearly abnormal for
the stated gestational sac size, the likelihood of pregnancy progression is unlikely. The presence of a
normal hCG concentration for a specified gestational sac measurement does not necessarily predict a
successful outcome.146
The accuracy of diagnosing pregnancy failure has been enhanced by ultrasonography.
Incomplete spontaneous abortion is characterized by disorganized intrauterine echoes, irregularity of
the gestational sac, frequent eccentric sac location, and the evidence of intradecidual hemorrhage.147
The anembryonic pregnancy (blighted ovum) is characterized by a visible gestational sac (chorion), but
no apparent fetal pole. Frequently the sac is smaller than expected.143,148,149 When the mean sac
diameter minus the crown-rump length is less than 5 mm, 94% of pregnancies were lost.150 Retention
of a discernible embryo that has undergone an early demise has been termed a missed abortion.
First-trimester hydatidiform mole may produce bizarre echoes in early pregnancy or may
initially appear as an unremarkable gestational sac.149 The ultrasound characterization of hydatidiform
mole has been well described. The early diagnosis of molar pregnancy enhances appropriate
management and hopefully minimizes the likelihood of malignant sequelae. Although variable, the
echo pattern suggestive of a molar pregnancy consists of irregular solid and cystic interfaces within the
endometrial cavity in a patient with signs and symptoms of early pregnancy (Fig. 48).

EXTRAUTERINE PREGNANCY. Pregnancies located outside the intrauterine cavity are

referred to as extrauterine pregnancies. Although these pregnancies include ovarian pregnancies,
abdominal pregnancies, and cervical pregnancies, the most common location is in the fallopian tube.
This section addresses the preclinical diagnosis of unruptured tubal pregnancies using a combined
approach of ultrasonographic findings correlated with serum hCG concentration.
Currently, as noted earlier, a discriminatory zone of approximately 1000 mIU/mL is being
used by means of transvaginal ultrasonography as the level at which a normal gestational sac should be
seen.132 The lack of visualization of the gestational sac with hCG concentrations greater than 1000
mIU/mL or an inadequate rate of increase of hCG is suggestive of the diagnosis of extrauterine
pregnancy and warrants further evaluation.132,151
Using transvaginal ultrasound and an hCG discriminatory zone of 1500 mIU/mL (1st IRP),
Barnhart and colleagues152 noted that all viable intrauterine pregnancies that were visualized by
ultrasound demonstrated hCG values in excess of 1500 mIU/mL. In a study of 1253 patients, there
were 205 ectopic pregnancies diagnosed by the combined use of serial hCG measurements and
transvaginal ultrasound. Fifty-nine percent of ectopic pregnancies never produced hCG concentrations
greater than 1500 mIU/mL. In their experience, the sensitivity of this combined protocol was 100% and
the specificity 99%.
A word of caution is justified. Multifetal pregnancies typically demonstrate a higher
discriminatory zone of hCG. Kadar and co-workers153 noted that a discriminatory zone of 3000
mIU/mL would be required in order not to misdiagnose early potentially viable multifetal pregnancy.
Since the hCG doubling time is relatively short (2 to 3 days), this difference in discriminatory
hCG levels does not translate into a long period of time, but as noted in the study mentioned earlier,152
most ectopic pregnancies do not achieve an hCG level of 1500 mIU/mL, much less 3000 mIU/mL. If
one wants to minimize the risk of intervening in a potentially normal intrauterine pregnancy, it seems

13
that a discriminatory zone of 3000 mIU/mL and expected doubling time of 72 hours would be
preferable.
If this protocol is adopted, the physician must be assured of the patient's reliability and
potential for follow-up, having the ability to intervene rapidly if concerning symptoms develop. It must
be stressed that this diagnostic protocol applies to patients who are asymptomatic or minimally
symptomatic. Patients with an acute abdomen, vasomotor instability, or evidence of hemoperitoneum
on transvaginal scanning should be treated surgically.
Using the transvaginal approach, an extrauterine conceptus is frequently delineated with
ultrasonography, at which time definitive surgical therapy may be instituted.154,155 As noted above,
this technique allows assessment of the cul-de-sac for fluid accumulation. If evidence of a possible
hemoperitoneum is seen, transvaginally directed culdocentesis can be readily accomplished.
Rarely, a combined intrauterine and extrauterine pregnancy (heterotopic pregnancy) may be
seen.156,157,158,159 The incidence of heterotopic pregnancy has been noted to be more frequent in
patients undergoing in vitro fertilization and warrants heightened awareness.160
The role of Doppler assessment to increase diagnostic accuracy is being evaluated. A
sensitivity of 73% for early evaluation was noted in a study of 96 ectopic pregnancies by Taylor and
co-workers161 using Doppler technology. Early diagnosis results in less morbidity, potential tubal
salvage, and the possibility of medical therapy.162
The assessment of eccentric intrauterine implantations is more difficult. The diagnosis of a
cornual or isthmic implantation site is frequently possible, and in these cases the early diagnosis
alleviates the potential for catastrophic uterine rupture.163 Chronic and interstitial ectopic pregnancies
producing complex adnexal echogenic masses have been described.164,165,166,167

14
 DIAGNOSTIC OBSTETRIC IMAGING
The role of ultrasonography in obstetric practice has continuously evolved since its introduction
more than 35 years ago. In the past decade, real-time ultrasound has led to significant advances in
obstetric care attributable to improvements in both image resolution and clinical correlation. Using this
imaging technique, clinicians can detect pregnancy as early as 3 weeks after conception, confirm or
revise gestational age within 1 week, diagnose multiple gestation in early pregnancy, confidently
diagnose fetal death at any gestational age, assess fetal well-being, evaluate amniotic fluid volume, and
diagnose a broad variety of fetal malformations.

CONTENT OF AN ULTRASOUND EXAMINATION

A basic ultrasound examination should contain a fetal survey, an evaluation of fetal biometry,
and documentation of the anatomic images obtained. The survey includes a confirmation of fetal
number, viability, position, assessment of amniotic fluid volume, and location of the placenta. In
assessing fetal biometry, the applicable standard fetal measurements already discussed, including CRL,
BPD, abdominal circumference, and femur length, should be taken. The estimation of fetal weight is a
clinically useful parameter obtained from the fetal biometric measurements. Several equations have
been produced based on fetal biometry that estimate fetal weight. One or more of these usually is
incorporated into the software of ultrasound machines. An estimation is provided automatically after
the biometry is recorded. These weight estimations differ little in accuracy, and most provide an
estimated fetal weight that has a standard deviation of ±8% to 10%. Therefore, 95% (2 standard
deviations) of estimations are within 20% of the actual birth weight.
An ultrasound examination also should include specific documentation of fetal anatomic images
obtained. These images are usually stored in the form of Polaroid pictures, videotape, thermal prints, or
digital image files.

USE OF ULTRASOUND AS A SCREENING TEST

Generally recognized indications for obstetric ultrasound imaging are found in Table 2.
Although the routine use of ultrasound in early pregnancy is not considered the standard of care by any
public organization in the United States,10 it is promoted by many practitioners. Some investigators
have noted a significant reduction in the frequency of labor induction for postdate fetuses when routine
ultrasound is performed. Routine ultrasound early in pregnancy can result in a significant revision of
the estimated date of delivery in up to 10% of patients with an accurate, normal last menstrual period.
Routine ultrasound use may decrease the incidence of antepartum fetal assessment and induction of
labor for postdate fetuses.
Belfrage and colleagues11 compared the routine use of ultrasound in early pregnancy with the
use of ultrasound for selected indications. Routine ultrasound use resulted in correction of the estimated
date of confinement by more than 2 weeks in 7% of cases. There also was a significant reduction in the
incidence of labor induction for postdate fetuses in the routine ultrasound group. Neonatal outcome was
similar in both groups.
The use of ultrasound as a routine screening tool in obstetric patients applies to low-risk patients
who have none of the indications shown in Table 2. The multicenter Routine Antenatal Diagnostic
Imaging with UltraSound (RADIUS) study intended to determine the clinical benefits of routine
ultrasound in a low-risk population.12 Patients were recruited from 109 obstetricians and family
practitioners from private, academic, and health maintenance organization practices. Of the initial
patient population of some 53,800 patients, in the final analysis, only 15,530 patients (29%) of the
initial registered group were randomized to receive either selected or routine ultrasound. The study

15
concluded that there was no benefit to routine ultrasound in this low-risk population. The RADIUS
study has been criticized in that the patients selected for final inclusion in this study bear little
similarity to the average obstetric population. Only about one third of fetal anomalies were detected
antenatally. If only serious malformations are considered, the detection rate was significantly improved
at 78%. Clearly, the detection of anomalies in tertiary centers was significantly more accurate than that
in primary care ultrasound clinics.
The Helsinki ultrasound trial included 9310 women: half were randomly allocated to ultrasound
screening and half to routine obstetric care.13 In the ultrasound screening group, perinatal mortality
was significantly lower by a factor of about 50%, mainly because of improved early detection of major
malformations in the group randomized to ultrasound, which led to an increased rate of pregnancy
termination. It also appeared in this trial that twin pregnancies detected earlier had a lower perinatal
mortality rate.
Clearly, the use of ultrasound as a screening test is a controversial matter. The most likely
benefits of ultrasound screening in low-risk patients are obstetric and include confirmation of dates,
early detection of multiple gestation, location of the placenta, and baseline growth data. In virtually
every complication that may occur later in pregnancy, clinical decisions may be facilitated if the patient
had an ultrasound earlier in pregnancy.
To be used as a screening test, ultrasound should be widely available and have a relatively low
cost and high sensitivity and specificity rates. One of the stated intents of the RADIUS study was to
determine whether routine ultrasound screening would improve perinatal outcome. Ultrasound,
however, is a diagnostic modality, not a therapeutic one. Ultrasound alone cannot reduce perinatal
mortality, but the information obtained from an ultrasound can be used to guide the clinician to choose
the appropriate therapy. In the final analysis, whether ultrasound is used as a screening test may depend
on its cost.
In the RADIUS study, about two thirds of the subjects were thought to have an obstetric
indication for ultrasound; however, it is only in the small proportion of truly low-risk patients that a
screening ultrasound should be considered. Should every obstetric patient have a routine ultrasound
examination? Only if it is adequately performed, properly recorded, and the patient is counseled
regarding appropriate goals and limitations of ultrasound.
Routine screening is best done between 18 and 20 weeks' gestation. At this time, the fetus
usually is large enough that the fetal anatomy can be surveyed well, and yet the gestation is early
enough that the accuracy of biometric measurements is preserved.

CLINICAL APPLICATIONS
Ultrasound estimation of fetal weight can be invaluable in many clinical situations, such as
obstetric management of the patient presenting with labor or ruptured membranes and no previous
prenatal care.
Identification of fetal macrosomia also is of particular interest to the clinician because this
condition is associated with an increased risk of a variety of obstetric complications. The accuracy of
ultrasound in predicting macrosomia depends on the clinical situation in which the ultrasound is
used.32 In a diabetic patient, if the ultrasound-estimated fetal weight predicts macrosomia, and the
abdominal circumference is at or above the 90th percentile, then the accuracy of ultrasound in the
diagnosis of macrosomia approaches 90%.33 In the diabetic patient, calculating the fetal chest diameter
(at the level of the fetal heart) and subtracting the BPD may allow predelivery prediction of
macrosomia with increased accuracy. A chest diameter more than 1.4 cm larger than the BPD was 87%
accurate in predicting a fetal weight of 4000 g or more in one study.34 The clinical utility of these
observations is limited, however, and any management decisions must take all other clinical features
into account, such as presentation, progress in labor, clinical pelvimetry, and obstetric history.

1. DIAGNOSIS OF PREGNANCY BY
ULTRASONOGRAPHY

16
 In the presence of leiomyomas or ovarian cysts, gestational age may be overestimated. The
availability of high resolution abdominal probes and transvaginal probes frequently clarifies the nature
of the mass and provides for more accurate dating (Fig. 1, Fig. 2). The transvaginal probe also allows
for high resolution images of the uterine endometrium and more frequent identification of uterine
anomalies (Fig. 3). In the presence of uterine pathology, the combined use of ultrasound and endoscopy
may aid in pregnancy terminations.1
Ultrasonography is also useful in the objective determination of gestational age. Assessment of
pregnancy dates from the menstrual history is imprecise;2,3,4,5 physicians who base their judgments
solely on this history may in some situations make incorrect estimates of gestational age. This can
effect the safety of pregnancy termination if the wrong procedure is used.6 Accurate determination of
gestational age is also critical in the management of preterm labor, postdates pregnancy, and in
scheduling elective cesarean sections at the appropriate gestational age.
The impact of the use of ultrasonography on the practice of obstetrics has been profound. Given
but one choice from the many biochemical and biophysical techniques that have been developed in
more recent years to try to improve pregnancy outcome, sonography would seem the best. Methods for
evaluating the health of the fetus that apply pulse-echo ultrasound are now employed widely for many
reasons that will be summarized in this chapter and illustrated frequently throughout the book.
Ultrasonic techniques that are now available, when performed carefully and interpreted accurately, can
supply vital information about the status of the fetus, with no confirmed biological hazards from
ultrasound (American College of Obstetricians and Gynecologists, 1993; American Institute of
Ultrasound in Medicine, 1991).
Since the first obstetrical application of ultrasound imaging by Donald and co-workers (1958),
ultrasonic evaluation of the pregnant uterus has become commonplace. For example, by 1989, 45
percent of pregnancies—1.7 million women in the United States— underwent sonographic evaluation
(National Center for Health Statistics, 1992). Because of the current impetus for cost-effective
medicine and outcomes-based research, the National Institutes of Health commissioned the Routine
Antenatal Diagnostic Imaging with Ultrasound (RADIUS) trial, which has sparked a lively debate
concerning its findings. Indeed, the Office of Medical Applications of Research (1995) of the National
Institutes of Health held a workshop in December 1993 to discuss implications of the RADIUS trial.
First Trimester. Early pregnancy may be evaluated with abdominal or vaginal ultrasonography.
Information listed in Table 44–2 should be obtained. Using abdominal scanning, the gestational sac is
reliably seen by 6 weeks menstrual age and fetal echoes and heart activity by 7 weeks. With
transvaginal scanning, these are seen about 1 week earlier (American College of Obstetricians and
Gynecologists, 1993).
Early sonography is valuable in confirming blighted ovum or an embryonic pregnancy, missed
abortion, and suspected ectopic pregnancy (see Chap. 27 ). Finally, multifetal gestation can be
identified and the number of amnions and chorions possibly determined.

Vaginal sonography section

In thin patients, transvaginal ultrasound (TVS) allows for the evaluation of early pregnancy
structures approximately 1 week earlier than transabdominal ultrasound. In markedly obese patients,
TVS may visualize early gestational sacs and embryonic structures weeks before the transabdominal
technique. TVS has the added advantage of being performed with an empty bladder, making the
procedure much more comfortable and acceptable to patients.
By using high-frequency vaginal transducers, Warren and colleagues have shown an orderly
appearance of embryonic and extraembryonic structures (Table 1).7 The early visualization of a
chorionic gestational sac, yolk sac, and fetal pole can be correlated with b-human chorionic
gonadotropin (b-hCG) findings to aid in the early diagnosis of intrauterine pregnancy, ectopic
pregnancy, and missed abortion (Table 2).8

EARLY PREGNANCY

As reported by Goldstein and co-workers,9 the high-frequency vaginal transducer allows

visualization of a chorionic gestational sac with a mean diameter of only 4 mm (Fig. 4) and a b-hCG

17
level of 1025 mIU using the First International Reference Preparation (IRP). This b-hCG level is called
the discriminatory zone, or the level at which an intrauterine pregnancy should be ultrasonically
visualized. As shown in Table 2, Fossum and associates8 using the transvaginal technique reported a
slightly higher discriminatory zone of 1400 for the First IRP. By comparison, an abdominal transducer
can only resolve a gestational sac when the mean diameter is approximately 10 mm and the b-hCG
level is either 6500 mIU or 3600 mIU (First IRP), depending on whether static or high-resolution
equipment is used abdominally.10,11
Fossum and associates8 also compared the appearance of early pregnancy structures by the First
IRP and the Second International Standard (see Table 2). Due to the large number of b-hCG assays,
each practitioner must be aware of the assay being used by their lab to establish discriminatory zones.
The Second International Standard will have discriminatory b-hCGs approximately 50% less than the
First IRP. Inability to visualize an intrauterine pregnancy sac using a high-frequency vaginal probe
when the b-hCG reaches the discriminatory zone raises the possibility of abnormal early pregnancy
including ectopic gestations. However, the practitioner must realize that there are limitations to using
discriminatory zones in clinical practice. Early gestational sacs may not be visualized at a given
discriminatory b-hCG level in cases of multiple gestation, incomplete abortion, or complete abortion.
Leiomyomata of the uterus may also obscure visualization of early gestational sacs and embryonic
structures.9

EARLY PREGNANCY LOSS

Batzer and colleagues12 using transabdominal technique initially proposed that the appearance
of the intrauterine gestational sac, yolk sac, and fetal pole can be correlated with the b-hCG titers to
assess risk for early pregnancy loss. Initially b-hCG titers are expected to double within 36 to 48-hour
intervals.12 Bree and co-workers13 using TVS found that a intrauterine gestational sac, yolk sac, and
fetal pole with fetal heart tones should be visualized at b-hCG titers greater than 1025 mIU, 7200 mIU,
and 10,800 mIU, respectively (First IRP). Risk for early pregnancy loss is also increased when the
mean sac diameter is 10 mm and a fetal pole is not seen. Similarly if the mean sac diameter is 20 mm, a
fetal pole with fetal heart tones should be seen.14 Similarly, positive fetal heart tones should always be
demonstrated when the fetal pole measures 5 mm or more.15

ECTOPIC PREGNANCY

The combination of b-hCG quantitative assays and TVS allows for more timely diagnosis of
ectopic pregnancy. Failure to see a gestational sac at 35 days from the last menstrual period or at a b-
hCG of 1025 mIU/ml is associated with an increased risk of ectopic gestation. The clinician must be
aware that early gestational sacs can be confused with pseudogestational sacs. Pseudogestational sacs
represent either fluid or blood within thickened endometrium or decidua (Fig. 5)16 By comparison, a
true gestational sac is noted eccentrically placed adjacent to the endometrial stripe (see Fig. 4). The
appearance of the yolk sac within an intrauterine sac at 35 to 49 days from the last menstrual period
unquestionably identifies an intrauterine gestational sac (Fig. 6).
Among emergency room patients, Timor-Tritsch and associates17 have shown that TVS is
highly accurate in diagnosing ectopic pregnancies, with a sensitivity of 100%, a specificity of 98%, a
positive predictive value of 98%, and a negative predictive value of 100%. Additionally, these
investigators have positively identified fetal heart motion in 23% of ectopic pregnancies, a much higher
frequency than the 5% to 10% rate possible by abdominal sonography (Fig. 7). Earlier diagnosis of
ectopic pregnancy can allow for increased use of operative laparoscopy and methotrexate
therapies.18,19,20

2. DETERMINATION OF GESTATIONAL AGE

In the past gestational age was established by a combination of the historical information and
the physical examination. Reliance was placed on the menstrual history and the maternal sensation of

18
fetal movement ("quickening"). Other factors include assessment of uterine size by bimanual
examination in the first trimester, initial detection of fetal heart tones by Doppler (10-12 weeks) or
auscultation (19-21 weeks), and uterine fundal height measurement. However, both the history and the
findings on physical examination are fraught with error, even in the best of circumstances (Table
1).6,7,8 It has been estimated that 20% to 40% of women cannot relate the LMP with certainty.6,7
Some of the reasons for this uncertainty include oligomenorrhea, metrorrhagia, bleeding in the first
trimester of pregnancy, pregnancy following use of oral contraceptives or intrauterine devices, and
becoming pregnant in the postpartum period. Hertz and co-workers9 reported that menstrual history
was considered reliable in only 18% of women. In another report, even among women with known
LMP, neonatal age assessment differed markedly from that assigned by certain menstrual dates in
15%.8 Physical examination also tends to be inaccurate, especially with advancing gestational age.10
Bimanual examination in the first trimester may be accurate within ±2 weeks; however, fundal height
measurement, which is more commonly used to assess gestational age, is only accurate within ±4 to 6
weeks. Clearly, the inaccuracies of history and physical examination may limit their usefulness in
assessment of gestational age. Methods that assess the time of ovulation or conception can accurately
establish gestational age.11,12,13,14 Timed ovulation, either by basal body temperature recording or
semiquantitative assessment of luteinizing hormone surge, predicts gestational age within ±4 to 6 days.
Ovulation induction with agents such as clomiphene citrate and Pergonal, also accurately predicts
gestational age. In vitro fertilization, with known date of conception, is likely the most accurate means
of predicting gestational age (±1 day). However, in most pregnancies, the date of ovulation or
conception cannot be as accurately predicted as outlined above and gestational age must be established
by other methods.

The advent of ultrasound has allowed a more direct means of assessing fetal structures and
development. Measurements of a wide variety of parameters have been devised to establish gestational
age. Ultrasound assessment of gestational age is feasible in a majority of pregnancies and may be used
to establish gestational age with greater accuracy than physical examination. In the first trimester,
gestational sac mean diameter and crown-rump length measurements have become the primary means
of evaluating gestational age.15,16,17,18,19 In the second and third trimesters, fetal head, body, and
extremity measurements have been commonly used to assess gestational age. Those parameters most
commonly measured include biparietal diameter,20,21,22,23,24,25,26,27,28 head circumference,29,30
abdominal circumference,31,32,33,34,35 and femur length.36,37,38,39 Although numerous other
parameters have been measured and related to gestational age, few offer any improvement in the
accuracy of gestational age assessment.40,41,42,43,44,45,46 In this chapter, the most widely used and
accepted ultrasound-derived fetal growth parameters are discussed and a review of their accuracies and
potential errors is presented.

A number of ultrasonically derived fetal parameters can be used to estimate menstrual

gestational age, including the binocular distance,21 the diameter of the cerebellar bodies,22 fetal foot
length and heel ossification centers,23,24 head circumference,25 abdominal circumference,25 crown-
rump length (CRL),26 biparietal diameter (BPD),27,28,29 and femur length.30,31
In this chapter, we will discuss only the CRL, BPD, and femur length because they are the most
accurate predictors of dates, as well as the most commonly used measurements for estimating
menstrual age.

Human pregnancy lasts an average of 280 days from the first day of the last menstrual period in
patients with regular 28-day menstrual cycles. Both clinical and ultrasonographic gestational age are
expressed using this standard.
The earliest ultrasonic evidence of pregnancy is the finding of a fluid-filled gestational sac with
an echogenic border. This finding may be seen with abdominal ultrasound as early as 5 weeks from the
last menstrual period, at which time it is about 11 cm in size. By 6 weeks, the sac doubles in size, and
in a normal pregnancy, a fetal pole becomes visible. At 7 weeks' gestation, fetal cardiac activity can be
seen. After this time, the presence or absence of fetal cardiac activity is an accurate method of
determining fetal viability.

19
 The use of endovaginal ultrasound has greatly enhanced our ability to detect pregnancy early.
Using a vaginal probe, the gestational sac and fetal pole can be found earlier than with the abdominal
approach. A gestational sac should be visible at 4 weeks and 4 days, and cardiac activity is seen at 6
weeks.1 The endovaginal transducer eliminates the need for a full bladder before examination and
significantly improves resolution in obese patients.

A single parameter (CRL, BPD, HC, AC, or FL) may be used to assess gestational age. The
accuracy of a single parameter is dependent on the gestational age at the time of ultrasound
examination (Table 9). Several methods have been employed to improve the accuracy of gestational
age assessment compared with the use of a single parameter. Two of these methods, growth-adjusted
sonographic age79 and averaging multiple parameters80,81 are discussed. Several principles are
important to remember when assessing gestational age by ultrasound:

1.When menstrual dates fall within the confidence limits of the ultrasound assessment, the role
of ultrasound is to confirm menstrual dates.
2.When menstrual dates fall outside the confidence limits of ultrasound assessment, assignment
of dates should be based on ultrasound assessment of gestational age.
3.When menstrual dates are unknown, assignment of dates should be based on ultrasound
assessment of gestational age.

Gestational age, synonymous with menstrual age, is defined in weeks beginning from the first
day of the last menstrual period (LMP) prior to conception. Accurate determination of gestational age is
fundamental to obstetric care and is important in a variety of situations. For example, antenatal test
interpretation may be dependent on gestational age. Specifically, the level of a-fetoprotein in both
amniotic fluid and maternal serum is related to gestational age and when dates are inaccurate test
results will be incorrect and misleading.1 Similarly, the magnitude of increased optical density above
baseline at 450 nm (delta OD 450) by amniotic fluid spectrophotometric measurement is used to
predict the severity of fetal hemolytic disease in pregnancies complicated by rhesus
isoimmunization.2,3 Test results are interpreted based on Liley's zones relative to gestational age.
Again, inaccurate assessment of gestational age will lead to errors in assessing the severity of fetal
sensitization by the delta OD 450. Fetal growth assessment, either clinically or by ultrasound
evaluation, also relies on accurate assessment of gestational age. Fetal growth retardation or
macrosomia may be missed or incorrectly diagnosed owing to errors in gestational age assignment.
Interpretation of antenatal biophysical testing (non-stress tests and biophysical profiles) may be subject
to variation with gestational age as well. Fetal heart rate reactivity and fetal breathing develop with
advancing gestational age; therefore, the absence of these biophysical parameters may be interpreted as
abnormal for fetuses in whom the gestational age has been overestimated. Obstetric management is
also dependent on gestational age. Proper decisions regarding presumed preterm labor or postdate
pregnancies are only possible when gestational age is accurately estimated. Likewise, timing of repeat
cesarean section requires accurate assessment of dates.4,5 Ultrasound is a reliable method for
establishing the length of pregnancy and in this way can improve obstetric care.

Fetal Measurements. There are many tables and nomograms that describe the normal growth
of various fetal dimensions. Among the most commonly measured dimensions are crown–rump length,
biparietal diameter, abdominal circumference, and femur length. There also are nomograms for other
fetal dimensions such as head circumference, length of the humerus, ulna, tibia, and clavicle, and
binocular distance. As emphasized by Jeanty (1991), deciding which table(s) to use can be difficult. It
also is important to emphasize that most predictions of gestational age are based upon the 50th
percentile measurement observed in normal fetuses. However, there is a wide range of normal
percentiles (5th through 95th) for a given fetal dimension. For example, a biparietal diameter of 40 mm
could represent a fetus of 14 weeks (5th percentile) or 20 weeks (95th percentile) as compared with 17
weeks when the 50th percentile is used. Jeanty (1991) reviewed thoroughly the many considerations
necessary in the selection of appropriate nomograms for estimating gestational age and fetal size. A
combination of measurements is superior to a single measurement. Importantly, most ultrasound

20
machines now are available with microcomputers and software that permit instantaneous calculation of
fetal indices such as fetal weight estimates.
Different fetal dimensions have different reliability and ease of measurement at different
gestational ages. Shown in Tables 44–4 and 44–5 are commonly used gestational age nomograms for
crown–rump length, biparietal diameter, head circumference, abdominal circumference, and femur
length. Shepard and co-workers (1982) have reported formulas frequently used for estimation of fetal
weight using the biparietal diameter and abdominal circumference.

First-Trimester Assessment
In the first trimester, the gestational sac mean diameter and crown-rump length are used to
establish fetal age. Both parameters are useful because each measures a different aspect of the first-
trimester pregnancy and may be used at different times during the first trimester.

GESTATIONAL SAC MEAN DIAMETER.

The gestational sac is the first identifiable structure routinely imaged in the first trimester. It is
identified by transabdominal ultrasound as early as 5 weeks' gestation and may be seen as early as 4
weeks' gestation by transvaginal ultrasound.15,16,47 The gestational sac is an echo-free space
containing the fluid, embryo, and extraembryonic structures. The sac is measured inside the
hyperechoic rim, including only the echo-free space (Fig. 1). The gestational sac is imaged first in the
longitudinal plane, obtaining long axis and anteroposterior measurements perpendicular to each other.
Then, in the transverse plane at the level of the anteroposterior measurement, the width measurement is
obtained. The three measurements are averaged to obtain the gestational sac mean diameter. Table 2
compares gestational ages from 5 to 12 weeks with the gestational sac mean diameters.15 The accuracy
of gestational sac measurement as a predictor of gestational age has been evaluated in only one report
and was found to be approximately ±1 week.16

CROWN-RUMP LENGTH.
The crown-rump length (CRL) is a measurement of the embryo, usually identified at 6 to 7
weeks' gestation.17,48 The embryo is measured along its longest axis to obtain the CRL measurement
(Fig. 2). Crown-rump length may be used to accurately date pregnancy between 7 and 13 weeks'
gestation. The technique involves measurement of the fetal length from the tip of the cephalic pole to
the tip of the caudal pole. The fetus should be at rest and assuming its natural curvature. At 5 to 6
weeks' gestation, distinct landmarks cannot always be identified but heart motion usually can be
detected centrally. As the pregnancy continues, the head can be easily identified from the rest of the
body. After 12 weeks' gestation excessive curvature of the fetus may lead to erroneous shortening of
CRL measurement; therefore, other measurements, such as the biparietal diameter, should be used to
estimate gestational age.
The correlation between sonographic CRL values and dates was first reported by Robinson
and Fleming, who obtained CRLs in pregnancies of women with certain menstrual histories.17 Drumm
and associates18 performed a similar study; however, their patients fulfilled more stringent dating
criteria. These early studies suggested that gestational age assessment by CRL was extremely accurate,
approaching ±3 to 4 days. Subsequent studies have suggested that the CRL is somewhat less accurate;
however, the accuracy is still within ±5 to 7 days.49,50,51,52 Most recently, MacGregor and co-
workers19 evaluated CRL measurements in pregnancies of women with known dates of ovulation and
reported data that differed from those of the previous two studies. Table 3 summarizes the results of
these three studies evaluating gestational age relative to CRL.
Variations in the measurement of CRL can be attributed to differences in fetal growth patterns.
Such differences are related to factors similar to those that influence birth weight curves, including
maternal age and parity, prepregnancy maternal weight, geographic location, and population
characteristics.53,54,55 Indeed, the existence of subpopulations with altered CRL growth patterns has
been suggested by previous reports.56,57 Technical factors can also lead to errors in CRL
measurements. These include incorporation of the yolk sac or lower limbs in the CRL measurement,

21
excessive curling or extension of the fetus, and tangential section of the trunk.17 Despite these
potential sources of error, CRL measurement is an accurate and useful method of assessing gestational
age in the first trimester.

Robinson and Fleming first described the methodology of localizing the longitudinal axis of
fetuses between 7 and 13 weeks of gestation for the purpose of measuring the fetal CRL.32 He
subsequently showed that the fetal CRL can be used to predict gestational age with an accuracy of ±5
days in 95% of the population. The reproducibility of the CRL is ±1 mm. MacGregor and colleagues
related CRL measurements to a group of women with known ovulation dates.26 They showed that
CRLs derived from menstrually dated pregnancies32 underestimated dates by 5 days in the interval
between 7 to 9 weeks, and by an overall average of 3.5 days. Thus, they recommended use of a chart
based on more reliable ovulation dates (Table 3). Other researchers have also noted a similar
discrepancy between CRL and early dates, as follows:
CRL = 1 cm at 49 days (7 weeks), Robinson and Fleming32
CRL = 1 cm at 57 days (8 weeks and 1 day), Selbing and Fjallbrant33
CRL = 1 cm at 56 days (8 weeks), Rossavik and coworkers34
CRL = 1 cm at 54 days (7 weeks and 5 days), MacGregor and colleagues26
An easily remembered formula is gestational age (days) = early embryonic size (mm) + 42.35

The crown–rump length (CRL) of the fetus is an accurate predictor of gestational age.2 A
practical approximation is that fetal CRL in centimeters plus 6.5 equals gestational age in weeks. A 9-
week fetus, for example, would have a CRL of 2.5 cm (Fig. 1). CRL has been promoted as the most
accurate method of dating a pregnancy, but experience has shown that the average of the biparietal
diameter (BPD), femur length, and abdominal circumference obtained before 20 weeks' gestation is
comparable in accuracy.3

Second- and Third-Trimester Assessment

Biparietal Diameter
In the second trimester of pregnancy, the ultrasonically derived fetal BPD can be used to predict
gestational age. The accuracy of the prediction is such that in relation to a given BPD obtained at 14 to
16 weeks of gestation, the length of pregnancy varies by ±7 days (2 SD).27 If the BPD is obtained at 17
to 26 weeks' gestation, the accuracy of predicting dates is within ±11 days in 95% of the population.27

BPD STANDARDIZATION. The first published ultrasonography charts showed a marked

variation in the specific BPD values used to predict mean gestational age.28 The variations were
assumed, at least in part, to represent population differences. Subsequently, however, we showed that
the mean BPDs obtained from both black and white fetuses were almost identical, particularly in the
first half of pregnancy.27 Furthermore, careful analysis of a number of well-designed studies in which
BPDs were derived by similar ultrasonographic methodology showed no statistically significant
differences in the cephalic measurements of a heterogeneous population of fetuses.28 These findings
led to the development of a composite mean BPD chart (Table 4).28
Although this composite BPD chart can be universally used to predict menstrual age, its
applicability to gravidas residing in geographic areas of high altitude, where mean fetal BPDs may be
smaller, remains to be elucidated.

BPD VERSUS 24-WEEK LIMIT. It is generally accepted that a pregnancy should not be
terminated when menstrual age exceeds 24 weeks because the fetus in question may have attained
viability. Thus, it is important to define the upper limit of the BPD beyond which pregnancy should not
be terminated.
A BPD of 6 cm is equivalent to a mean gestational age of 24 weeks (see Table 4), but this
prediction varies by ±11 days (2 SD)—that is, from 22 weeks and 3 days to 25 weeks and 4 days.
Fetuses with biologically small BPDs are more advanced in gestational age than is apparent from the

22
mean BPD chart (Fig. 8). By the same token, fetuses with biologically large BPDs are less mature than
is apparent from the mean BPD chart.29
Because the gestational age in a particular fetus can only be assessed within a margin of ±11
days, the validity of terminating the pregnancy in gravidas with a fetal BPD of 6 cm may be questioned
on the basis that some fetuses (statistically estimated to represent 20% of the group with a BPD of 6
cm) may be more advanced in gestational age by 7 to 11 days. Similarly, the duration of pregnancy in
20% of gravidas with a fetal BPD of 6.4 cm (or 25+ weeks' mean gestation) may, in fact, fall within the
24-week range.
It is apparent that the BPD value predicting the 24th week of gestation or the limit beyond
which pregnancy should not be terminated is difficult to ascertain. Nonetheless, when strict adherence
to an upper limit of 24 menstrual weeks is mandatory, the selected BPD should not exceed 5.7 to 5.8
cm.

After the first trimester, CRL determination is not practical because of fetal posturing and size.
From 12 weeks onward, the BPD is one of several useful estimators of fetal gestational age. The BPD
is the largest transverse measurement of the fetal skull and usually is measured from an occipitofrontal
scan plane at the level of the fetal thalami and the septum pellucidum cavum (Fig. 2). The fetal head
should have an oval shape with clear midline margination. The measurement is determined, by
convention, from the outer edge of the proximal fetal parietal bone to the inner edge of the distal
parietal bone (Fig. 3). The gestational age is estimated by comparing the observed BPD to tables
relating BPD to gestational age.
Because of increasing biologic variation with advancing gestational age, the precision of
estimated gestational age from BPD is greatest early in the second trimester. Between 14 and 20 weeks,
the BPD correlates with gestational age within 1 week in 95% of cases. Late in the third trimester, the
measured BPD may predict gestational age within only 3 to 4 weeks.4,5
In about 5% of cases, BPD cannot be obtained because of fetal position; in a fetus in
occipitoanterior or occipitoposterior presentation, the proper plane of the fetal skull cannot be
visualized. Deferring the study for a short time allows the fetus to assume a more favorable position. If
an appropriate BPD cannot be obtained, an alternative fetal dimension is chosen.
The occipitofrontal diameter is measured in the same plane as the BPD and is a measurement of
the longitudinal axis, by convention taken from outer skull tables on each side. This measurement can
be averaged with the outer-to-outer skull measurement in the transverse plane to provide a basis for
estimating head circumference. The cephalic index is the ratio of the transverse to longitudinal
diameters measured in a similar fashion; a normal cephalic index is 0.78 + 0.05. An abnormal cephalic
index in not necessarily indicative of fetal pathology, but BPD measurements may be inaccurate
estimators of gestational age if the fetal head is either more oval (dolichocephalic) or more round
(brachycephalic) than average.6 A low cephalic index, for instance, often is seen in breech
presentations.
The biparietal diameter (BPD) is one of the most commonly measured parameters in the fetus.
Campbell was the first investigator to link fetal BPD to gestational age20; however, since this original
report, numerous publications on this subject have appeared in the
literature.20,21,22,23,24,25,26,27,28,58,59,60,61,62,63 The BPD may be rapidly and reproducibly
measured by ultrasound examination from 12 weeks' gestation until the end of pregnancy. The BPD is
imaged in the transaxial plane of the fetal head at a level depicting thalami in the midline, equidistant
from the temporoparietal bones and usually the cavum septum pellucidum anteriorly (Fig. 3).58,59
Although several methods have been used to measure BPD, the most commonly accepted method is
measurement from leading edge to leading edge (outer-to-inner) (see Fig. 3).
Gestational age assignment is based on the mean BPD; however, a single BPD encompasses a
range of ages in which most fetuses of that size are most likely to fall (Table 4).23 The accuracy of fetal
age assessment based on BPD is dependent on gestational age.22,23,27,28,51,58 Between 12 and 26
weeks' gestation, the BPD is accurate to within ±10 to 11 days. After 26 weeks' gestation, the accuracy
of BPD measurement progressively decreases and is ±3 weeks near term. A number of factors may
contribute to variation or inaccuracy in the BPD measurement. Biologic variation, for example, may
occur because of differences in maternal age, parity, prepregnancy weight, geographic location, and
specific population characteristics. Technical factors including interobserver error, different techniques
of measurements, and single versus multiple measurements may likewise influence the accuracy of

23
BPD in assessing gestational age.60,61,62 Although most dating curves show the same general
relationship between BPD and gestational age, there are often significant differences in gestational age
assignment for any particular BPD measurement. Furthermore, BPD measurement is most accurate in
assessing gestational age when the head shape is appropriately ovoid. If the head is unusually rounded
(brachycephalic) or unusually elongated (dolicocephalic), BPD measurements would overestimate or
underestimate gestational age, respectively. To determine whether head shape is appropriate, Hadlock
and co-workers64 compared the BPD and the frontooccipital diameter. The ratio of these diameters is
called the cephalic index (CI), with a mean value of 0.78 and a normal range (±2 SD) of 0.70 to 0.86.
In the fetus with an abnormal cephalic index (noted in <2% of fetuses prior to 26 weeks' gestation),
dates may be estimated more accurately using other fetal parameters, such as head circumference.

Growth-Adjusted Sonographic Age

Gestational age estimation using a single biparietal diameter is accurate within a margin of
±10 to 11 days in the second trimester. Gestational age can be more accurately predicted by obtaining
paired BPD measurements (the first from 20 to 26 weeks' gestation and the second from 31 to 33
weeks' gestation) and assigning gestational age by a method developed by Sabbagha and co-workers79
known as growth-adjusted sonographic age (GASA).
In approximately 90% of fetuses, BPD growth from 20 to 33 weeks' gestation tends to
progress within narrow percentile ranks (Table 10).21,25 BPD growth patterns can be subdivided into
three types: large (90th percentile); average (10th to 90th percentile); and small (10th percentile).
Paired BPD measurements obtained at different gestational ages allows categorization of the specific
cephalic growth pattern. The first measurement should be obtained between 20 and 26 weeks' gestation,
and the second measurement should be obtained between 30 and 33 weeks' gestation. The first BPD
measurement will not distinguish the fetus with large, average, or small BPD growth, and, therefore,
the fetus is assigned a mean gestational age based on an assumed average BPD growth pattern. The
second BPD measurement identifies the specific type of growth pattern. For example, in the fetus with
average growth the second BPD measurement will fall between the 10th and 90th percentiles,
confirming the gestational age assignment from the first BPD measurement. In contrast, BPD growth in
the small-for-gestational age fetus will follow a slow growth pattern and the second BPD measurement
will be less than or equal to the 10th percentile for the gestational age assigned by the first BPD. Since
the first BPD measurement failed to recognize the small growth pattern and, therefore, underestimated
gestational age, the second measurement allows the gestational age assessment to be adjusted based on
the BPD growth pattern. Such a fetus with a slowed growth pattern would have the gestational age
advanced by 1 week at the time of the second BPD measurement. Similarly, dates in the large-for-
gestational age fetus may be adjusted by GASA at the time of the second BPD measurement,
decreasing gestational age assignment by 1 week if the BPD measurement is greater than or equal to
the 90th percentile (Fig. 6). Use of GASA has been reported to increase the accuracy of gestational age
estimation by BPD measurement to within ±3 to 5 days.79
The method of GASA has not been used when the first BPD measurement is obtained prior to
20 weeks' gestation; therefore, it is best to confine the use of GASA to pregnancies in which serial
ultrasound studies are contemplated and the first measurement is obtained between 20 and 26 weeks'
gestation. Smazal and associates51 evaluated the method of GASA and suggested that the accuracy was
indeed ±5 days. However, in this report, the accuracy of a single BPD was also approximately ±5 days.

Head circumference.
The head circumference (HC) measurement may be used to estimate gestational age in a similar
manner to BPD measurement (Table 5).30 Although tracing of the outer perimeter of the head (by
trackball on the ultrasonic equipment or by digitizer) is the most reliable means of measuring HC, the
following formula using biparietal and fronto-occipital diameters may be used to calculate HC with a
maximum error of 6%:63,65

(D1 + D2)/2 3.14

24
 The accuracy of gestational age estimation by HC measurement is comparable with that of BPD
measurement.30 However, in fetuses with abnormal head shape, either brachycephaly or dolicocephaly,
HC may be a more accurate predictor of fetal age than BPD.30,65

Measurement of Fetal Long Bones. Femur Length

Measurement of the fetal limb bones also may be used to determine gestational age. The femur
length usually is chosen because of its relative positional stability. The measurement is obtained by
aligning the transducer with the lower end of the fetal spine and rotating toward the ventral aspect of
the fetus.7 At first, only part of the femur may be seen; slight rotation and angulation of the transducer
allows the entire length to be imaged. When properly visualized, the femur should have clear distal
margins. Often, the bone casts a shadow to help identify this landmark (Fig. 4). The ultrasound images
typically do not include epiphyses in early gestation; therefore, 8% to 15% of the palpable bone is not
measured. Because the reference tables were derived in this fashion, accuracy is preserved.
As is the case with BPD, the reliability of femur length in prediction of gestational age is best in
early pregnancy. In the third trimester, however, femur length shows less variation than the BPD.
Femur length may be difficult to obtain in a breech presentation, and measurement of the fetal humerus
provides a good alternative. The humerus usually can be identified arising from the lateral upper fetal
chest.

The osseous shaft of the femur is one that is an easy fetal bone to image and measure. However,
the accuracy of estimating dates by femur length is quite controversial, and the measurement is subject
to a wide interobserver variability of 4.4 mm.36
O'Brien and colleagues30 showed that in the first part of the second trimester of pregnancy, the
femur length was accurate within a 2 SD range of ±7 days (Table 5). In another study, however, the
range in dates relative to femur length widened with advancing gestation, from ±11 days to ±3 weeks in
the second and third trimesters of pregnancy, respectively.31 On the other hand, Jeanty and colleagues
reported a ±2.8 week variation in dates relative to femur length at any time in pregnancy.37
The controversy in the accuracy of the femur length may stem from a number of variables,
including the following:

1.Differences in the number of patients entered into each study; the biggest group was that
studied by Jeanty and colleagues.37
2.Lack of strict adherence to accepted methodology; only the osseous portion of the femur
should be included in the measurement.38
3.Measuring the femur length in the horizontal rather than the axial plane. Axial values are
significantly smaller than lateral values.39 Pretorius and colleagues found that the absolute error in
lateral measurements fell into the range of 0 to 12 mm, whereas that noted in axial measurements was
only between 0 and 4 mm.40

Despite these differences, the femur length is useful in assessing pregnancy dates, particularly in
fetuses at high risk for having an abnormally small or large cephalic size, such as in microcephalus,
dolichocephalous (side-to-side flattening of the fetal head), hydrocephalus, and brachycephalus. By the
same token, the femur should not be used to predict menstrual age in gravidas at high risk for skeletal
dysplasia because its length may be abnormally small.

All the fetal long bones can be adequately examined and measured by ultrasound; however, the
femur is the largest of the long bones, least moveable, and easiest to image. The femur may be
adequately visualized from 14 weeks' gestation until delivery.38,39,40,67,68,69,70,71,72,73,74 It is
measured along the long axis of the bone; a straight measurement of the osseous portion is taken from
one end to the other, disregarding bone curvature (Fig. 5). The femoral neck and both proximal and
distal epiphyseal cartilages are excluded from the measurement. Femur length (FL) measurements may
be used to accurately predict gestational age between 14 weeks' gestation and term (Table 8).39 Most
observers consider the accuracy of the FL and BPD measurements to be similar in the third trimester.
Although there is controversy regarding the accuracy of the FL prior to 26 weeks' gestation,38,39 the

25
accuracy of gestational age prediction based on FL is greatest in the second trimester and least near
term.
Biologic variation may lead to inaccuracies of FL measurements in a manner similar to that of
the other fetal growth parameters. In addition, several technical factors are potential sources of error in
the measurement of the femur.67,70,72 Sector ultrasound imaging may lead to overestimation of FL,
particularly when the femur is in the far field or lateral margins of the image. Linear-array ultrasound
imaging provides more accurate measurements of FL. In addition, FL measurements obtained in the
axial plane (parallel to the ultrasonic beam) have less mean absolute error than those obtained in the
lateral plane, perpendicular to the ultrasonic beam (1.7 mm vs. 3.7 mm, respectively).74 Tangential
section of the femur, failing to visualize the entire length of the shaft, leads to underestimation of FL
and, therefore, of gestational age. Artifactual bowing of the femur may also occur on ultrasound
imaging and lead to a shortened FL measurement. The distal femoral epiphysis becomes echogenic in
the third trimester and is separated from the distal end of the diaphysis, the osseous portion of the shaft.
Inclusion of the distal epiphysis will falsely overestimate FL.67,68
Gestational age assessment by FL is particularly useful when head measurement is difficult to
obtain due to fetal position. The femur length may also be compared with the biparietal diameter
(FL/BPD) as an age-independent ratio.73 The FL/BPD ratio (normal values 79 ± 6%) is useful as an
internal verification of the measurements obtained, as well as an indicator of pathologic entities, such
as microcephaly (FL/BPD abnormally high) and hydrocephalus or short-limb dysplasia (FL/BPD
abnormally low). Although the femur length and abdominal circumference (FL/AC) have also been
compared in order to diagnose fetal growth abnormalities (macrosomia and fetal growth retardation),34
there is much overlap between normal and abnormal values of this ratio.75,76,77,78

Abdominal Circumference
The fetal abdominal circumference, or mean abdominal diameter, also is useful in predicting
gestational age.8 This measurement is obtained in a transverse plane, perpendicular to the fetal spine, at
the level of the stomach and umbilical vein (Fig. 5). The fetal image in this transverse plane is nearly
circular; the abdominal circumference is the average of the anteroposterior and transverse diameters,
measured from outer diameter to outer diameter. The circumference can be obtained by multiplying the
mean abdominal diameter by p (about 3.14), or by directly measuring the circumference using a
perimeter system on the ultrasound image, which is provided on most current ultrasound systems.

Measurement of the fetal abdominal circumference (AC) is obtained in the transaxial view of
the fetal abdomen. The AC is measured at the level of the fetal liver, using the umbilical portion of the
left portal vein as a landmark (Fig. 4). The fetal stomach is at the same level, which is slightly caudad
to the fetal heart and cephalad to the kidneys. The AC measurement is taken from the outermost aspects
of the fetal soft tissues. Measurement of the AC is performed in the same manner as that of the HC, that
is, by (1) tracing the outer perimeter of the AC by the trackball on the ultrasonic equipment or by
digitizer or (2) the same equation as for HC using transverse and anteroposterior diameters of the fetal
abdomen. The AC may be used to estimate gestational age (Table 6) but is less accurate than head
measurements (BPD or HC).33 Similar to head measurements, the accuracy of AC in estimating
gestational age is greatest in the second trimester, with decreasing accuracy near term. Biologic
variation and technical factors may contribute to the inaccuracy of AC measurements in a manner
similar to that previously described for bi-parietal diameters. Of particular note, the abdominal
circumference is the growth parameter most commonly affected in pregnancies complicated by
abnormal fetal growth patterns.33 A macrosomic fetus will have increased AC relative to gestational
age, and an asymmetrically growth-retarded fetus will have diminished AC measurements. Variation in
AC measurements in macrosomic and growth-retarded fetuses is due to differences in liver size and
width of subcutaneous tissue in these two types of abnormal growth patterns. Thus, estimation of
gestational age by AC will lead to inaccuracies in fetuses displaying either of these growth patterns.
However, the HC/AC ratio may be useful as a predictor of head-to-abdomen symmetry or asymmetry
in order to identify the type of abnormal growth (Table 7).66

26
Multiple Predictors
The most accurate parameters for dating pregnancy are CRL measurements from 6 to 13 weeks
and BPDs from 14 to 26 weeks. However, when two or more parameters predict the same end point,
the probability of the accuracy of that end point is increased (Bayes' theorem).25 Thus, it is important
for a sonographer to measure different parameters to determine whether there is any similarity in the
estimation of dates. The following guidelines can be followed:

1.When menstrual dates fall within confidence limits of any one or more parameters, the role of
ultrasonography will be to confirm menstrual dates.25
2.If the menstrual age estimates derived from two or more ultrasonic parameters are within 1
week of each other and the pregnancy is normal (no growth retardation or macrosomia is suspected), it
is justifiable to assign dates from the average of these parameters. This approach is referred to as
selective averaging. It involves averaging the ultrasonographic parameters that predict a similar end
point.
3.When menstrual dates fall outside the confidence limits of one or more ultrasonographic
parameters, dates may be assigned by the most accurate ultrasonographic predictors (CRL, BPD
between 14 and 26 weeks) if altered growth can be ruled out.

The relation between ultrasonographically derived fetal dimensions and gestational age is purely
empiric. The older a normal fetus, the larger it is. The reproducible ultrasonographic measurement of
any fetal dimension in a normal reference population of fetuses of known gestational age allows the
construction of a regression relation between that dimension and age. Subsequently, the determination
of the gestational age of a pregnancy for which the conception date is unknown can be made by
comparing that dimension with the reference data (Table 1).
Averaging the gestational ages derived from two or more measurements has been shown to be
more accurate than using any single parameter.9 Determinations made early in pregnancy are more
accurate than those made later. Because of the greater accuracy of the early study, ultrasound
examinations subsequent to an early study should not be used to change the estimated date of
confinement (EDC), but rather should be used as a measure of the quality of fetal growth between the
two studies. Similarly, it is not appropriate to revise an EDC on the basis of an ultrasound examination
if the patient's menstrual dates are within the range of error of the ultrasound method.
If significant discrepancy is seen between two ultrasonographically measured fetal dimensions
(more than a 2-week difference), the ultrasonographer must consider the possibility of an error in
measurement technique. If a critical reevaluation reveals no error, then asymmetry in fetal growth may
be present. Growth asymmetry may occur as a result of physiologic alteration in fetal head shape
(brachycephaly or dolichocephaly) or in association with intrauterine growth restriction (IUGR) or a
fetal anomaly.

Hadlock and co-workers80,81 combined several measurements in an effort to increase the

accuracy of gestational age assessment. The rationale for employing multiple parameters for fetal
dating is that when two or more parameters predict the same end point, the probability of correctly
predicting that end point is increased. The BPD, HC, AC, and FL measurements were obtained and the
mean gestational ages of combinations of these parameters were averaged to obtain a mean gestational
age. The use of multiple parameters improved the accuracy of gestational age assessment compared
with any single parameter (Table 11).80 If the gestational age estimates derived from all of the
parameters are similar, assignment of gestational age from the average of all the parameters will
improve accuracy. However, if gestational age estimates of the various parameters are quite different,
averaging multiple parameters will decrease the accuracy of the best predictor(s). Averaging of fetal
growth parameters should be avoided when certain conditions are suspected, such as fetal macrosomia,
intrauterine growth retardation (both symmetric and asymmetric), and congenital anomalies (skeletal
dysplasias, hydrocephalus, and others).

27
Multiple Gestations
The detection of multiple gestations is important since multiple gestations are at greater risk
for many complications, particularly fetal growth retardation. Fetal biometric data are available for
twin gestations81,82,83,84,85; however, triplet and quadruplet pregnancies have not been adequately
studied owing to their infrequent occurrence.
In general, ultrasound-derived fetal dating tables obtained for singleton pregnancies can be
used accurately for twin pregnancies until approximately 30 weeks' gestation.82,83,84,85,86 During
the last 10 weeks of pregnancy there is a decrease in the growth rate for twin fetuses compared with
singleton fetuses. Grumbach and co-workers86 have suggested that the femur continues to grow
normally throughout pregnancy in twin gestations, while the head (BPD and HC) and abdominal (AC)
growth rates decrease in the last 10 weeks of pregnancy. Although further studies are required to
confirm these findings, this study suggests that FL measurement may be a more reliable parameter to
use for gestational age assessment in twin gestations during the third trimester. Gestational age
estimations in twin pregnancies prior to 30 weeks' gestation should be performed in a similar manner to
that for singleton pregnancies.

Summary
A simple, but uniform approach to the evaluation of gestational age should be performed in all
fetuses. The ultrasound assessment of fetal age is based on the earliest ultrasound study, provided the
measurement is technically adequate. Early in gestation fetal measurements have the least variability
and, therefore, are most likely to predict fetal age. In the first trimester, the CRL measurement is used
to estimate gestational age, whereas in the second and third trimesters fetal head (BPD and HC), body
(AC), and extremity (FL) measurements are used to assess gestational age. The following guidelines
are recommended for the assessment of gestational age:

1.Crown-rump length measurement is used to establish fetal age in pregnancies with unknown
menstrual dates or in pregnancies with discrepancy between menstrual dates and crown-rump length
measurement of greater than ±7 days. If CRL and menstrual dates are within the normal range of error
of the measurement (±7 days), the menstrual dates are used to establish fetal age.
2.In the second trimester, menstrual dates are used if the mean gestational age predicted by (a) a
single parameter (BPD, HC, or FL) or (b) multiple parameters (BPD or HC and FL ± AC) is within the
range of error of these measurements. If menstrual dates are unknown, or the difference between
menstrual dates and the mean gestational age predicted by single or multiple parameters is greater than
the range of error of these measurements, fetal age should be established using the best ultrasound
predictors (either single or multiple parameters) or GASA method.
3.In the third trimester, gestational age assessment is particularly problematic. Menstrual dates
should be used to establish fetal age if the mean gestational age predicted by multiple parameters is
within the range of error of these measurements (±2-3 weeks). In the pregnancy with unknown
menstrual dates or a discrepancy between menstrual dates and mean gestational age predicted by
multiple parameters of more than 3 weeks, fetal age should be estimated by the multiple parameters
method. However, the potential error of this method in the third trimester of pregnancy may not be
acceptable. Obstetric management must appreciate this potential for error. For example, a patient
presenting in spontaneous labor at 33 ± 3 weeks' gestation should be managed as if the pregnancy may
be as little as 30 weeks' gestation, rather than as advanced at 36 weeks' gestation. Similarly, the patient
presenting for prenatal care at 39 ± 3 weeks' gestation, should be managed for the potential of postdates
pregnancy.

Use of the multiple parameters method of assessing gestational age is valid when the
gestational age estimates of the various ultrasound parameters are similar. If the gestational age
estimates of one or several parameters is greater than 2 weeks different than the estimates of the other
parameters, either the abnormal ultrasound parameters should be excluded or a different method should
be used to estimate gestational age. When the various ultrasound parameters predict different

28
gestational ages the fetus should be further evaluated to explain these differences. For example, an
abnormally small FL measurement may suggest short-limb defects, a large BPD may be secondary to
hydrocephalus, and an abnormally small or large AC measurement may suggest asymmetric
intrauterine growth retardation or macrosomia, respectively. As mentioned previously, the different
ultrasound ratios (CI, HC/AC, and FL/BPD) may be used to identify abnormally small or large
parameters. In the instance of an abnormal cephalic index, the HC should be used to estimate
gestational age, rather than the BPD measurement.
In conclusion, assessment of gestational age is fundamental to obstetric care and should be a
carefully thought-out process. Assessment should depend on history and physical examination, as well
as ultrasound evaluation.

3. ASSESSMENT OF FIRST-TRIMESTER
COMPLICATIONS
First-trimester ultrasonography can be of significant value in predicting the outcome in patients
with bleeding in early pregnancy. Except in the unusual circumstance of a combined pregnancy
(incidence 1 in 30,000), the finding of a pregnancy within the uterus excludes an ectopic pregnancy.
This distinction, however, is not always clear. The normal gestational sac has a well-defined, echogenic
border. In ectopic gestation, decidua and blood may distend the uterine cavity, and the ultrasound image
can mimic a gestational sac, resulting in the so-called pseudogestational sac.14 These entities often can
be distinguished by ultrasound; in a pseudogestational sac, the echogenic rim usually is absent, ill
defined, or not centrally positioned in the uterus.15 In questionable cases, serial growth of the sac can
be assessed. In a normal pregnancy, the gestational sac should grow at least 0.6 mm daily.16
Using a quantitative assay of human chorionic gonadotrophin (hCG) with ultrasound improves
diagnostic accuracy. Even with b-hCG values as low as 750 mIU/mL, a gestational sac can be
visualized.17 If the level is below this value, in a clinically stable patient, serial HCG values can be
followed. In a normal early pregnancy, the b-hCG level should increase at least twofold in 72 hours.
In practice, a clinical problem often faced is differentiation of a threatened abortion from an
ectopic pregnancy. In both these conditions, a subnormal rise in b-hCG usually is seen. Ultrasound
findings in a pregnancy destined to abort include a poorly defined gestational sac, a large yolk sac (6
mm), a low site of sac location in the uterus, or an empty gestational sac at 8 weeks' gestational age—
the blighted ovum.
The only absolute assurance that a pregnancy is intrauterine is the finding of a fetal pole within
the uterine cavity. The endovaginal ultrasound can be useful in this clinical setting because the fetal
pole can be seen at 6 weeks. In a normal pregnancy, the fetal pole should be visible if the gestational
sac is 25 mm or larger in diameter.
The presence of a fetal pole with demonstrable cardiac activity is reassuring and greatly
decreases the likelihood of spontaneous abortion. In an ultrasonically normal gestation without
bleeding at 8 to 9 weeks, there is a 3% chance of subsequent pregnancy loss.18 If bleeding is present,
this chance increases to about 13%.19
Also included in the differential diagnosis of vaginal bleeding in pregnancy is the hydatid mole,
which has a characteristic ultrasound appearance (Fig. 6).

4. EVALUATION OF FETAL GROWTH ABNORMALITIES

Fetal growth can be evaluated by comparing individual dimensions to normative data, by
comparing various fetal dimensions to assess symmetry, or by integrating selected measurements to
produce an estimation of fetal weight.
Several investigators have derived equations useful for estimating weight, using fetal
dimensions, such as BPD, mean abdominal diameter, abdominal circumference, and femur length.
Warsof and colleagues24 first provided a clinically useful formula for weight estimation using BPD
and AC. Shepard and co-workers25 reported a second similar equation with slightly improved
accuracy. Rose and McCallum26 described a system using the sum of the BPD, mean abdominal
diameter, and femur length in centimeters that is relatively easy to use. The differences between these
and other published methods is small when compared with the overall accuracy of fetal weight

29
estimation. Generally, the ultrasonic predicted weight is within 10% of the actual weight in two thirds
of cases and within 20% in 95% of cases.
In the preterm fetus in which clinical estimation of fetal weight is notably inaccurate, estimating
fetal weight using ultrasound is useful. In the term fetus, however, because of the greater actual error,
ultrasound-estimated fetal weight may be no more accurate than a clinical weight estimation.27
If the gestational age in a pregnancy is confidently established, ultrasound can provide an
accurate diagnosis of IUGR. IUGR can result from uteroplacental insufficiency, drug exposure,
intrauterine infection, or genetic factors.35 Symmetric IUGR, in which all fetal parameters are small
for a given gestational age, occurs with extrinsic conditions that are active early in pregnancy (e.g.,
tobacco or alcohol abuse, congenital rubella). Symmetric IUGR also can result from intrinsic
conditions that limit fetal growth potential (e.g., chromosomal abnormalities). Symmetrically reduced
growth also is seen in the constitutionally small, normal fetus.
Fetal growth may be normal until the late second or early third trimester, at which time the limit
of uteroplacental circulation in sustaining fetal growth is reached. This results in asymmetric fetal
growth, in which the fetus adapts to the relative decrease in uteroplacental blood flow by redistributing
cardiac output to favor the brain at the expense of the muscles and abdominal viscera.
For these reasons, the use of BPD alone can detect only half of IUGR cases. When IUGR is
suspected, ultrasound-estimated fetal weight can detect up to 90% of affected infants.36,37 An
estimated fetal weight below the 10th percentile for gestational age is predictive of IUGR. When IUGR
is suspected, the ultrasonographer should look critically at amniotic fluid volume. Oligohydramnios,
resulting from decreased fetal urine production as blood is shunted away from the fetal kidneys,
commonly is associated with severe IUGR. Manning and associates38 noted that when a 1-cm pocket
of amniotic fluid could not be found, IUGR was present in 90% of cases.38 The amniotic fluid index
also has been described as a useful tool in the evaluation of fluid volume.39
When the gestational age is not precisely known, assessment of fetal growth during a 2-week
period is useful in distinguishing IUGR from incorrectly dated pregnancies. In the third trimester, fetal
weight should increase about 300 g in 2 weeks. Another gestational age–independent assessment is the
abdominal circumference/fetal length or mean abdominal diameter/fetal length ratio.40 Reece and co-
workers41 reported that the transverse fetal cerebellar diameter is unaffected by IUGR; this additional
parameter may help to discriminate IUGR from incorrectly dated pregnancies.

5. ASSESSMENT OF THIRD-TRIMESTER BLEEDING

Ultrasound examination is useful in differentiating causes of third-trimester bleeding. The
placenta can be identified easily with the real-time scanner. Placenta previa can be diagnosed with a
high degree of accuracy (Fig. 7). In cases of marginal previa, the examination should be done with both
an empty and a full bladder for greatest accuracy. The internal os may be located by identifying the
bladder angle in a moderately full bladder.
Apparent placenta previa is an incidental finding in 5% of second-trimester scans done for other
indications. In marginal previa or central previa (central insertion of the placenta over the cervix) seen
on a second-trimester scan, a follow-up scan in the third-trimester is indicated; more than 90% of these
cases have spontaneously resolved on subsequent examination because of asymmetry in uterine
growth, not placental migration.28,29
Other causes of third-trimester bleeding include abruptio placentae and vasa previa. Although
these conditions have been diagnosed with ultrasound, they cannot be excluded confidently in most
cases. A retroplacental clot may be seen in some cases of abruptio,30 but ultrasound cannot exclude
abruption, and the wise course in most cases is to treat the patient as clinical circumstances dictate.
With increasing gestational age, the placenta increases in echogenicity because of increased
fibrosis and calcium content. This feature of placental maturation has led to a grading of placentas from
immature (grade 0), to mature (grade 3).31 In a grade 3 placenta, individual cotyledons are outlined by
dense fibrotic calcified septa. The correlation of a grade 3 placenta with fetal pulmonary maturity is
high. A grade 3 placenta can be observed in the third trimester in a variety of high-risk fetal conditions
(e.g., IUGR, chronic hypertension) but also can occur in normal pregnancy. Conversely, a grade 3
placenta may not be seen in many normal patients in labor at term.

30
6. EVALUATION OF MULTIPLE GESTATIONS
In evaluating multiple gestations, the ultrasonographer should note the number and presentation
of the fetuses and the position and number of placentas. A membrane almost always can be seen
between each fetus in early gestation. Monoamniotic twins, which comprise only 3% of all twin
gestations, have no intervening membrane and are at much greater risk of perinatal mortality than other
twins. The thickness of the membrane between twins may provide a clue about whether both chorion
and amnion are present because a thicker membrane is present in dichorionic-diamniotic twins.42
As is the case with ultrasound diagnosis of IUGR, discordance is better predicted by estimated
fetal weight calculation than by BPD alone.43 Discordance is determined by dividing the observed
fetal weight difference by the weight of the larger twin. Mild discordance (15% to 25% difference in
fetal weights) occurs in about 20% of twin pregnancies, and severe discordance (more than 25%
difference) occurs in about 5% of twins.44 Discordant twins are at increased risk for perinatal
mortality; the smaller twin is at greatest risk antenatally. A reasonable approach to assess growth in
twin gestation is to perform serial estimated fetal weight measurements on both twins every 4 weeks
beginning at 20 weeks' gestation. If discordance is present, or if intertwin weight differences are
increasing, weight determination is recommended more often.

7. DETECTION OF FETAL MALFORMATIONS

The ability of ultrasound to detect and characterize a broad array of fetal malformations is well
known. Ultrasound is best suited to the detection of obstructive malformations, or major distortions of
surface anatomy. Each ultrasound examination performed should comprise an anatomic survey of the
fetus, including cranial and intracranial structures, spinal anatomy, a four-chamber cardiac view, the
abdomen with stomach and umbilicus, the bladder, and at least one long bone. Any suspicion of
abnormality should result in referral for a more detailed ultrasound examination.
A basic office ultrasound examination is adequate for most patients. A targeted scan, performed
by an ultrasonographer with experience in the evaluation of fetal malformations, is done when there is
a suspected fetal abnormality on a basic ultrasound examination or to evaluate fetal anatomy when the
patient is in a high-risk category based on history, physical findings such as polyhydramnios, or
laboratory testing (e.g., AFP).
Determination of fetal karyotype should be considered in any case in which a malformation is
ultrasonographically detected. Aneuploidy is discovered in about 10% of cases of ultrasonographic
dysmorphology. The finding of a lethal karyotype could alter obstetric management because fetal
distress during labor often occurs in this setting, and a cesarean section delivery might otherwise result.
Additionally, the finding of one structural malformation should prompt a more detailed search for other
anomalies.45

Fetal Anatomy. Most attempts to survey fetal anatomy using ultrasound take place during the
early second trimester or later. Although some investigators have reported success with imaging various
fetal structures during the first trimester, Green and Hobbins (1988) generally were unable to identify
fetal structures transabdominally before 9 weeks; their success rate improved remarkably, however, as
gestation progressed. By 12 weeks, they were able to visualize the stomach in 95 percent, the anterior
abdominal wall in 80 percent, the adrenal glands in 100 percent, the kidneys in 100 percent, and the
bladder in 60 percent. Similarly, Timor-Tritsch and associates (1990) reported consistent success at
imaging the skull, brain, spine, limbs, and anterior abdominal wall in 35 fetuses examined
transvaginally between 9 and 14 weeks. By 11 weeks, they were able to visualize the fingers and feet.
Although there are increasing numbers of case reports that describe detection of a variety of
fetal anomalies during the first trimester, and in spite of the obvious potential for identifying congenital
fetal malformations at this point, caution is recommended for several reasons: (1) Normal first-
trimester embryological development may mimic pathological changes in the second and third
trimesters; for example, physiological anterior wall herniation may mimic an omphalocele. (2) Grossly
abnormal embryos may appear normal, as with anencephaly. (3) Some abnormal embryos may
manifest only with a crown–rump length that is less than expected for their gestational age (Levi and
associates, 1990).

31
 Caution emphasized by the American College of Obstetricians and Gynecologists (1993) is
worth repeating. Whichever method used, and regardless of the stage of pregnancy evaluated, it is
unrealistic and unreasonable to expect detection of all fetal anomalies even with the most expert
and thorough scanning. Some limitations of the routine 18 to 20 week scan are listed in Table 44–6.
Gonçalves and colleagues (1994) reported that the overall sensitivity of sonography in detecting fetal
defects was 53 percent. Overall specificity was 99 percent. Although the technique was highly sensitive
—89 percent—for detecting lethal malformations, it missed serious cardiac defects, microcephaly, and
many musculoskeletal deformities.

The recent development of high-resolution ultrasound equipment has markedly improved the
diagnostic accuracy of ultrasound. In particular, the introduction of high-frequency vaginal probes has
enabled early diagnosis of certain fetal abnormalities from the 12th to 14th week of pregnancy. Such
early testing is of special importance for women with a history of pregnancies associated with birth
defects. The frequency with which different organ systems can be imaged is shown in Table 1.1 The
sequential appearance of fetal neural structures during the first trimester of pregnancy is shown in Table
2.2
The examination for the detection of congenital anomalies is referred to as either detailed
ultrasound study or targeted imaging for fetal anomalies (TIFFA)3, 4 In such examinations, a variety of
fetal anatomic views ("targets"') are specifically sought after and imaged by experienced
ultrasonographers. The indications for TIFFA are listed in Table 3.
Despite these technical advances, ultrasound accuracy remains dependent on gestational age.
For example, if only one ultrasound examination is to be performed in the second trimester of
pregnancy, the best time would be between weeks 19 and 20. Accuracy also depends on the skill of the
ultrasonographer in obtaining the correct anatomic views and in differentiating between normal and
abnormal structures.
The ultrasonographer also plays an essential role in 1) interpretation of the pathophysiology of
a discovered defect, and 2) delineating the risk involved. For example, the risk for spina bifida in a
woman with elevated maternal serum alpha-fetoprotein is much lower if a detailed ultrasound study is
normal (Table 4).5 Thus, the need for amniocentesis to evaluate amniotic fluid alpha-fetoprotein (which
is a better predictor of spina bifida than maternal serum alpha-fetoprotein) should be reevaluated in
relation to the newly assigned risk (see Table 4).5 Similarly, the risk for autosomal trisomy is lower
than the age-related or maternal triple-screen risk in women with a normal second trimester fetal
ultrasound examination (Table 5, Table 6, Table 7 and Table 8).
TIFFA examinations entail ultrasonic visualization of at least 34 fetal views and measurement
of seven specific sites (Fig. 1). For each of these views, the ultrasonographer should indicate whether
the structure is normal, previously normal, not applicable, suspect, abnormal, or poorly visualized. Poor
visualization occurs when (1) fetal movement or position does not allow adequate imaging of a specific
area, or (2) gestational age is less than 19 to 20 weeks.
A normal TIFFA scan takes approximately 1 hour to complete. However, the presence of an
anomaly is likely to extend the study and make it necessary for the mother to undergo a combination of
genetic counseling, amniocentesis, or chorionic villi sampling to define fetal karyotype.
Studies that definitively resolve any possible concern regarding the long-term safety of
ultrasound as well as its cost:benefit analysis are not yet available.6
Ewigman and co-workers7 evaluated the efficacy of routine antenatal diagnostic imaging with
ultrasound (RADIUS) in reducing adverse perinatal outcome. Secondary outcomes included maternal
morbidity and diagnostic accuracy of ultrasound. Study subjects were recruited from 92 obstetric and
17 family medicine practices in six states. Selection was based on predefined entry criteria that placed
all study patients (screened group) in a low-risk category. Ultrasound screening examinations were
performed on 7812 study subjects during two pregnancy intervals: 15 to 22 weeks, and 31 to 35 weeks.
The women (n = 7718) in the control group had an ultrasound examination performed only if it was
clinically indicated. The sensitivity in the detection of congenital anomalies was significantly higher in
the screened versus control groups (34.8% vs 11%, p < 0.01); however, the higher detection of
anomalies did not result in improved perinatal outcome. Romero8 and others9, 10 attribute the lack of
improvement in perinatal outcome to (1) the limited sensitivity in the detection of anomalies in the
RADIUS study, and (2) the low rate of pregnancy termination in women diagnosed with a fetal
anomaly.

32
 The low sensitivity (16.6%) in the detection of anomalies in the RADIUS study, particularly
before 24 weeks' gestation, is very disturbing because it does not represent the current diagnostic
capability of ultrasound. Specifically, in four studies11, 12 13, 14 published from 1990 to 1992, the
sensitivity of ultrasound screening for congenital anomalies before 24 weeks' gestation was 40%,
60.7%, 74.4%, and 84.3%, respectively. The specificity and negative predictive values were greater
than 98%.11, 12, 13, 14 Except for the Helsinki trial,11 the positive predictive values in these studies
were equal to or greater than 98%.12, 13, 14

Head and Spine

Central Nervous System Evaluation. Prenatal sonography has proven an excellent method to
detect and characterize fetal central nervous system abnormalities. This is especially important because
of the frequency of these abnormalities as well as their potential for causing severe disability or death.
By adopting a systematic approach to the ultrasound evaluation of the central nervous system, it is
possible to identify virtually all fetuses with major abnormalities (Filly and colleagues, 1989). Such
early identification allows timely consideration of prognosis and therapeutic options, including
pregnancy termination.
Three routine transverse (or axial) sonographic views are recommended by Nyberg (1989) to
depict the fetal brain and cranium. The transthalamic view (Fig. 44–1 ), which is used to measure
biparietal diameter and head circumference, includes the thalamus, cavum septi pellucidae, and the
frontal horns of the lateral ventricle. Moving superiorly yields the transventricular view (Fig. 44–2 ),
which contains the lateral cerebral ventricles and the echogenic choroid plexus and also allows
visualization of cranial contour. The transcerebellar view (Fig. 44–3 ) is obtained by angling through
the posterior fossa in the suboccipital bregmatic plane, and demonstrates the cerebellum and cisterna
magna. Normal transverse cerebellar diameters for fetuses between 13 and 40 weeks have been
reported by Goldstein and associates (1987).
Filly and colleagues (1989) reported their experiences with 137 fetuses between 15 and 39
weeks who had sonographically diagnosed central nervous system abnormalities. Of these, 25 had
obvious anencephaly and 99 had a ventricular atrial diameter larger than 10 mm. Seven of the
remaining 13 fetuses had cisterna magna either smaller than 2 mm or larger than 11 mm in size. Using
this sequence of evaluation, only 6 of 137 fetuses with abnormal nervous systems were not identified;
however, in three of these fetuses, other grossly apparent abnormalities were seen. Thus, using a
relatively simple sequence of evaluation, 134 of 137 fetuses with central nervous system abnormalities
would have been identified. This same group also studied 150 normal fetuses between 15 and 40 weeks
and found that the ventricular atrium could be identified and measured in 99 percent and the cisterna
magna in 90 percent.
Monteagudo and associates (1991) found that transvaginal ultrasonography in the second and
third tri-mesters enhanced findings in fetuses with central nervous system abnormalities. Using this
approach, they changed the diagnosis in 5 of 13 fetuses. We have found transvaginal sonography to be
particularly helpful in the 16- to 20-week fetus to clarify neural-tube defects.
ANOMALIES OF THE CENTRAL NERVOUS SYSTEM

The frequency of central nervous system anomalies varies according to geographic area and
race. It is approximately 2:1000 newborns, and the recurrence risk is 1% to 2%.

ANENCEPHALY

In anencephaly, the cerebral hemispheres and overlying skull and scalp are absent. In
exencephalus, the cranial bones are also absent, but a large amount of disorganized brain tissue is
present. The diagnosis can now be made in the latter part of the first trimester of pregnancy with the
use of high-frequency transvaginal ultrasound (Fig. 19).60

33
MICROCEPHALY

The diagnosis of microcephaly is more likely to be accurate when the head circumference is 3
SD below the mean for dates (Table 12).4, 5 A definitive diagnosis is usually difficult to make before
24 weeks' gestation because the etiology is variable (Table 13), and head size may not become small for
gestational age until the third trimester of pregnancy.
Sonographic measurement of the frontal lobe (i.e., the distance from the posterior wall of the
frontal horn to the inner aspect of the skull) has been proposed as a helpful diagnostic tool because the
frontal aspect of the brain is the area most compromised.61, 62, 63 The normal frontal lobe values ± 2
SD from 16 to 24 weeks' gestation are shown in Table 14.

MENINGOCELE AND ENCEPHALOCELE

In cranial meningocele, the meninges protrude through a bony defect in the skull. Occipital
presentation of meningocele is most common, occurring in 75% of cases. The differential diagnosis of
cranial meningocele includes (1) scalp edema associated with fetal hydrops, (2) cystic hygroma, (3)
teratoma, and (4) encephalocele (Fig. 20).64, 65
Spina bifida is frequently associated with meningocele. The latter represents extrusion of the
meninges through the bony defect. Some cerebrospinal fluid (CSF) is usually contained within the
meningocele. As a result, the area appears cystic, an ultrasound characteristic that enhances visibility of
small spina bifida (Fig. 21).

CHOROID PLEXUS CYST

A choroid plexus cyst is visualized in approximately 1% of fetuses scanned at 16 to 22 weeks'

gestation (Fig. 26). In 1% to 2% of such fetuses, fetal trisomy 18 or 21 is noted.71, 72, 73, 74 Parents
therefore should be counseled regarding the assessment of fetal karyotype. They should also be
informed that trisomy 18 is a fatal condition, but that approximately 10% of infants with this defect live
beyond 1 year of age. These parents should be counseled with respect to the emotional and financial
cost of caring for an infant with this disorder.75
It has been postulated that the risk for aneuploidy may be small if (1) the cyst is less than 1 cm
in diameter, (2) the cyst decreases in size or disappears as the pregnancy advances to 22 weeks, and (3)
no other anomalies are noted. Whether there is indeed a decreased risk in such pregnancies, however,
remains controversial. Kupfermink and co-workers76 showed that in a fetus with isolated choroid
plexus cyst, the risk for aneuploidy is high (1:25) and thus amniocentesis is warranted.

THE POSTERIOR FOSSA

The posterior fossa shows the cerebellum and the cisterna magna (Fig. 27). Normally, the
cisterna magna measures 1 to 10 mm. The differential diagnoses of an enlarged cisterna magna include
trisomy 18, arachnoid cyst, and obstruction of normal CSF flow at the level of the foramina Luschka
and Magendie. CSF obstruction occurs in the following conditions:

1.Dandy-Walker malformation
2.Abnormalities of the subarachnoid space:
a. Arnold-Chiari II syndrome
b. Cerebral infection
c. Achondroplasia
d. Hurler syndrome.77, 78, 79

In Dandy-Walker malformation, dilation of the posterior fossa results from atretic foramina
Luschka and Magendie, hypoplastic cerebelli, and vermis (roof of the fourth ventricle). As a result, the
dilated fourth ventricle "herniates" into the area of the cisterna magna, ultrasonically appearing as

34
symmetrically dilated cisterna magna (see Fig. 27). In contrast, an arachnoid cyst in the posterior fossa
is less symmetric.77

HYDROCEPHALUS
The incidence of hydrocephalus ranges from 0.3 to 0.8 per 1000 births (Chap. 39 ). Fetuses who
are diagnosed prenatally have other intracranial or extracranial malformations or chromosomal
abnormalities in 85 percent of cases, and appear to have a very poor prognosis for normal long-term
development (Chervenak, 1983; Nyberg, 1987; Pretorius, 1985; and their colleagues).
Currently, the most accurate measure of ventriculomegaly is the lateral ventricle atrial
measurement. In the normal fetus, the diameter of the lateral ventricular atrium is relatively constant
from 6 to 9 mm between 15 and 35 weeks (Cardoza and colleagues, 1988b). Early in the second
trimester, the choroid makes up the majority of the ventricular volume, but it involutes with increasing
gestational age to become only a small portion of the volume by the third trimester (Fig. 44–4 ). An
atrial diameter greater than 10 mm suggests ventriculomegaly. This observation is especially useful, as
dilatation of the ventricular atrium and occipital horns is thought to be an early event in the
development of fetal hydrocephalus.
Cardoza and associates (1988a) examined the relationship between the choroid plexus and the
lateral wall of the dependent lateral ventricle. They compared 50 normal fetuses at 15 to 38 weeks with
25 hydrocephalic fetuses at 18 to 39 weeks. Mahony and colleagues (1988) quantified the anatomical
relationship between the choroid plexus and the medial wall of the dependent lateral ventricle. Their
findings suggest that a free-floating or dangling choroid plexus may facilitate the early diagnosis of
fetal hydrocephalus. In the presence of hydrocephalus, the heavy choroid plexus in the dependent
lateral ventricle will separate from the medial ventricular wall through the action of gravity.
Ventricular enlargement is not always due to hydrocephalus; it is also caused by brain
parenchymal destruction or colpocephaly (poor brain development). The combined use of the three
cranial views have led to very sophisticated antenatal diagnoses, based on their classical findings,
including aqueductal stenosis, holoprosencephaly, hydranencephaly, cerebral atrophy (secondary to
intrauterine infection or infarction), porencephalic cyst, agenesis of the corpus callosum, and
intracranial tumors.
Isolated Mild Cerebral Ventriculomegaly
ISOLATED MILD CEREBRAL VENTRICULOMEGALY. In about 25 to 50 percent of cases
of ventriculomegaly, the defect is mild and there are no associated abnormalities. The reports of Brown
and colleagues (1995) and Patel and associates (1994) indicate that about 20 percent of such infants
will manifest neurological abnormalities later in life. Those with borderline ventriculomegaly fare
better. As expected, those later found to have other abnormalities such as chromosomal anomalies or
evidence for intrauterine infection do poorly.
Hydrocephalus is most sensitively detected by measurement of the width of the lateral ventricle
at the choroid plexus. A value of 10 mm or less before 20 weeks' gestation is normal. In early
hydrocephalus, the choroid plexus may be displaced anteriorly and does not fill the atrium of the
ventricle. Early diagnosis is thus made on morphologic as well as measurement criteria. In later
gestation, the diagnosis may be made by comparing the distance to the lateral aspect of the ventricle
width relative to the cranial hemisphere width. The normal ratio of these measurements is dependent on
fetal gestational age.47

Figure 22 depicts the flow of CSF in hydrocephaly. Any lesion preventing normal flow of CSF
from the lateral ventricles to the cisterns results in hydrocephaly.
Obstruction at the level of the aqueduct of Sylvius results in enlargement of the third and
lateral ventricles (Fig. 23). The etiology of such obstruction includes (1) X-linked recessive inheritance,
(2) infection with cytomegalovirus or toxoplasmosis, and (3) other lesions that impinge on the area.
Hydrocephaly plus dilation of the posterior fossa results from obstruction of CSF flow at the
level of the foramina Luschka and Magendie (see Dandy-Walker syndrome, below). Table 15 lists a
number of other specific syndromes that result in hydrocephaly.

35
 In approximately 25% of hydrocephalic fetuses, an abnormal karyotype is found. Of these
fetuses, approximately 85%, have additional anomalies. Thus, the prognosis should be individualized
depending on specific etiology, but this cannot always be determined antenatally.
Hydrocephalic fetuses should not be delivered before pulmonary maturity is attained because
there is a weak correlation between the extent of compression of the cerebral cortex and the severity of
mental retardation.

ROUTE OF DELIVERY. In a term fetus with normal chromosomes, isolated hydrocephalus

(i.e., no other abnormality noted), and head circumference less than 90th percentile, vaginal delivery
may be a reasonable option. If head circumference is equal to or greater than 90th percentile at term,
cesarean section may be the least traumatic route. When hydrocephalus is associated with conditions
incompatible with life, such as renal agenesis, thanatophoric dwarfism, or trisomy 18, cephalocentesis
may be used to accomplish vaginal delivery. The combination of hydrocephalus with spina bifida also
can determine the mode of delivery (see section on Spina Bifida. below).
In contrast to simple ventriculomegaly, hydrocephalus usually is more progressive, and it is
frequently associated with compression of the choroid plexus (see Fig. 23).
The progression of hydrocephalus may be gauged by (1) the ventricular:hemispheric ratio, and
(2) the diameter of the ventricular atrium (see Fig. 22 and Fig. 23).66, ,68 Dilation of the ventricular
atrium is also a characteristic finding in agenesis of the corpus callosum. In such cases, the third
ventricle is displaced cephalad and the frontal horns laterally.69

DIFFERENTIAL DIAGNOSES. Differential diagnoses of hydrocephaly include the following:

1.Holoprosencephaly: In this condition, the cerebral hemispheres do not separate; a single

ventricle is noted, and hypotelorism is a characteristic finding. Fetal karyotype is abnormal in 50% of
fetuses with holoprosencephaly, and trisomy 13 is the most frequent chromosomal abnormality. The
diagnosis may be made in the latter part of the first trimester with the use of high-frequency vaginal
ultrasound (Fig. 24).
2.Hydranencephaly. In this condition, early bilateral vascular thrombosis of the carotid arteries
bilaterally results in infarcted and atrophic cerebral hemispheres. The cerebellum, midbrain, and basal
ganglia are seen, however. and are characteristically surrounded by a fluid interface.
3.Porencephaly. In contrast to hydranencephaly, the condition results from localized brain
atrophy secondary to a vascular accident.
4.Aneurysm of the vein of Galen (Fig. 25):70 Dilation of the vein of Galen results from an
arteriovenous malformation in which one or more arterioles feed the vein of Galen and distend it. The
diagnosis is clarified by color Doppler velocimetry (see Fig. 25). The distension may result in
hydrocephaly, and it may lead to high-output cardiac failure (see Fig. 25).

NEURAL-TUBE DEFECTS
Neural-tube defects result from failure of tube closure by the sixth gestational week (embryonic
age 26 to 28 days). A more detailed account of common neural-tube anomalies is found in Chapter 39 ,
and their incidence is cited in Table 39–8.
Anencephaly was the first fetal malformation to be diagnosed prenatally by using sonography.
Although its diagnosis is theoretically possible as early as 8 weeks, it can be missed by experienced
sonographers in the first trimester (Levi and associates, 1990). In the second trimester, however, if an
adequate ultrasound examination can be performed, anencephaly is diagnosed with virtually 100
percent accuracy. Sonographically, anencephaly is characterized by absence of the cranial vault and
brain above the base of the skull and orbits. Hydramnios, secondary to impaired fetal swallowing,
commonly accompanies anencephaly but is typically a late finding. Goldstein and Filly (1988) reported
increased amnionic fluid in 85 percent of anencephalic fetuses after 25 weeks, but in only about 10
percent before. Associated fetal anomalies are common but have not been extensively described
because anencephaly itself is uniformly fatal.
Encephalocele defines the condition in which the meninges and cerebrospinal fluid, usually in
association with brain tissue, herniate through a cranial defect. This lesion most commonly results from
an occipital midline defect. Sonographically, encephaloceles vary in size and are characterized by either

36
a cystic or solid appearance depending on which fetal structures are involved. Encephaloceles are
commonly associated with either hydrocephaly or microcephaly. The presence of an encephalocele is
an important feature of Meckel–Gruber syndrome and frequently accompanies amnionic band
syndrome. An occipital encephalocele can usually be detected using transthalamic and transcerebellar
views.
The incidence of fetal open neural tube defects in the United States is 1 to 2 per 1000 births.
Anencephaly, in which the cranial vault is absent, accounts for about half of these. By locating the fetal
spine and moving the ultrasound transducer cephalad, the absence of a cranial vault can be confirmed.
In anencephaly, the fetal orbits should be visible. The cranium should be visualized by 14 weeks'
gestation.

Spina bifida is more difficult to detect; the fetal spine must be meticulously examined in three
planes. Successful ultrasonographic detection of spina bifida requires examination of both spinal and
cranial anatomy. Experience strongly suggests that intracranial abnormalities are present in most all
cases of spina bifida.20,46 Five cranial signs associated with spina bifida are frontoparietal notching
(the "lemon" sign; Fig. 8), mild hydrocephalus, a small-for-date BPD, abnormal cerebellar
hemispheres, and obliteration of the cisterna magna. The finding of a normal fetal cerebellum and
cisterna magna virtually excludes spina bifida. This view is obtained by finding the axial plane of the
BPD and rotating the transducer to view the posterior fossa (Fig. 9).
Spina bifida consists of a hiatus, usually in the lumbosacral vertebrae, through which a
meningeal sac may protrude, forming a meningocele. If the sac contains neural elements, as it does in
90 percent of cases, the anomaly is called a meningomyelocele. Roberts and colleagues (1983)
reported their 6-year experience with the ultrasound diagnosis of spina bifida in a group of women at
high risk for an affected fetus. All studies were performed before 20 weeks, and in the first 3 years they
correctly diagnosed only 6 of 18 defects while they falsely diagnosed a defect in 49 of 1243 normal
fetuses. In the second 3 years of their study, they correctly diagnosed 16 of 20 defects and
misdiagnosed only 4 of 1171 normal fetuses. The importance of experience is apparent.
The fetal spine should be examined by sonography with sagittal, transverse, and coronal views
(Fig. 44–5 ) whenever possible. These provide the best opportunity to detect the presence and extent of
defects in the fetal spine and overlying soft tissues. Fetal movement of the lower extremities and
urination may be seen despite the presence of neurologically significant spina bifida.
Because of the difficulty in detecting small spinal defects, especially during the second
trimester, the association of cranial abnormalities with spina bifida has recently been the subject of
intense investigation. For example, spina bifida is commonly, if not invariably, accompanied by the
Arnold–Chiari malformation. Although the exact cause of this malformation is unclear, its pathology is
well characterized: the medulla and fourth ventricle are elongated and, in combination with a portion of
the cerebellum, extend through the foramen magnum into the upper cervical spinal canal. The Arnold–
Chiari malformation is felt to be responsible for sonographically detectable fetal abnormalities that
include cerebral ventriculomegaly, frontal bone scalloping (lemon sign), abnormal curvature of the
cerebellum (banana sign), decreased cerebellar size, and failure to visualize the cerebellum and
obliteration of the cisterna magna.
In spina bifida, splaying of the spine is noted in the longitudinal plane. However, small spinae
bifida located in the lumbosacral area are best visualized by careful cross-sectional imaging (see Fig.
21). The size of spinae bifida varies from a tiny bone defect to one involving many segments of the
spine (myeloschisis).
Importantly, an Arnold-Chiari type II malformation occurs in nearly all cases of spina bifida.
This is characterized by forward scalloping of the frontal aspect of the fetal head (lemon sign; see Fig.
21), and an abnormal, banana-shaped cerebellum (banana sign). The ultrasonographer should always
look for these signs during the examination; if they are present, the ultrasonographer should extend the
examination to search for spina bifida.80

MODE OF DELIVERY. Currently, there are no controlled prospective studies that indicate
whether a fetus with spina bifida should be delivered vaginally or by cesarean section. In a recent
retrospective report, however, Luthy and associates81 showed that the mean functional level of infants
delivered by cesarean section extended to a lower level than that of infants delivered vaginally (L4 vs
L2). This two-segment difference may determine the prognosis as to whether an infant will be able to

37
walk.81, 82 Thus, obstetricians prefer delivery by cesarean section because it allows controlled
handling of the fetal lumbosacral area.

Cerebral ventriculomegaly has been reported in approximately 80 percent of fetuses with spina
bifida. Although it generally is mild to moderate, it tends to worsen with advancing gestational age
(Goldstein and colleagues, 1989; Nyberg and co-workers, 1988). Benacerraf and co-workers (1989)
reported that a cerebellar banana sign was present in 22 of 23 fetuses diagnosed with spina bifida
between 16 and 27 weeks. Van den Hof and associates (1990) presented findings from 130 fetuses with
sonographically diagnosed spina bifida. A banana sign was found in 70 percent of 107 affected fetuses
before 24 weeks, and another 29 had an “absent cerebellum.” After 24 weeks, only 4 of the 23 fetuses
with spina bifida demonstrated a banana sign, but another 17 had an absent cerebellum. When the data
from these two studies are combined, a total of 1405 fetuses subsequently proven not to have spina
bifida were examined with ultrasound because of maternal risk factors for neural-tube defects, and
none had an abnormal cerebellum. In a related observation, Goldstein and colleagues (1989) evaluated
a group of fetuses between 17 and 38 weeks who were at risk for neural-tube defects. They obtained an
adequate view of the posterior fossa in 19 of 20 fetuses with spina bifida. In 18 of these fetuses the
cisterna magna was completely effaced, and in one it measured 2 mm. In all 33 of the nonaffected
fetuses, the cisterna magna measured 4 to 9 mm.
Normally, when visualized in the transthalamic or transventricular planes, the frontal contour of
the fetal cranium is convex. The presence of a concave or flattened frontal contour has been termed the
lemon sign (Fig. 44–6 ). In the study by Van den Hof and associates (1990), 105 of the 107 fetuses less
than 24 weeks old with spina bifida had this sign compared with only 3 of 23 after 24 weeks. Similarly,
Nyberg and associates (1988) found a lemon sign in 24 of 27 affected fetuses before 24 weeks,
compared with 8 of 25 fetuses later in gestation. Combining the two studies, however, only 12 of 1497
fetuses evaluated because they were at increased risk for neural-tube defects had a lemon sign in the
absence of spina bifida.

CHOROID PLEXUS CYSTS

Choroid plexus cysts have been identified in up to 3 percent of second-trimester fetuses
(Benacerraf and co-workers, 1990; Chinn and associates, 1990). The cysts vary in size from 2 to 20
mm. They are usually transient and will resolve by 24 weeks (Fig. 44–7 ). They may be associated with
chromosomal anomalies; the most common is trisomy 18, which is found in about 1 percent of these
fetuses.
Chitkara and associates (1988) detected choroid plexus cysts measuring 2 to 20 mm in 40
fetuses between 16 and 21 weeks. Approximately half were bilateral. Of the 40 cysts, 33 resolved by 23
to 24 weeks, and another 4 by 26 to 28 weeks. One fetus with large bilateral cysts and additional
ultrasound abnormalities had trisomy 18. Chan and co-workers (1989) prospectively studied 513
women who underwent genetic amniocentesis between 16 and 24 weeks. Thirteen fetuses had choroid
plexus cysts between 3 and 10 mm. Approximately one third were bilateral. All 13 fetuses had normal
karyotypes. Conversely, of the 500 fetuses without choroid plexus cysts, five had trisomy 21 and two
had trisomy 18.
Kupferminc and colleagues (1994) identified 102 fetuses (1.1 percent) with choroid plexus cysts
among 9100 pregnant women undergoing ultrasonic evaluation. Four fetuses had obvious associated
anomalies; two of these had trisomy 18 and a third an unbalanced translocation. The remaining 98
fetuses had choroid cysts as an isolated findings. In 75, amniocentesis was done and there were four
abnormal karyotypes—three Down syndromes and one trisomy 18. Because of a 1 in 25 risk of an
associated chromosomal anomaly with an isolated cyst, they recommend that amniocentesis be offered.
Conversely, Benacerraf and co-workers (1990) calculated that if all second-trimester fetuses with no
ultrasound abnormalities except choroid plexus cysts underwent genetic amniocentesis, 478 procedures
would have to be done to identify each case of trisomy 18. Gross and colleagues (1995) provided
substantiating data from 74 fetuses with isolated cysts. None of these had associated trisomy 18, and
their meta-analysis identified two cases among 748 such fetuses. They too argued against routine
cytogenetic testing in these cases. More recently, Leonardi and associates (1996) described 149 women
with isolated cysts at a mean of 19 weeks. There were 12 percent associated anomalies, including 4
percent aneuploidies. They recommended karyotype evaluation if there were associated minor or major

38
anomalies seen on sonography. The largest study comes from a registry of 524 fetal choroid plexus
cysts identified over 3 years in the Yorkshire region of the United Kingdom. Gupta and colleagues
(1995) also added cases from published prospective studies as well as 71 cases from Dundee, Scotland.
Their analysis totalled 1361 cases and they found that the risk of chromosomal anomaly was 1 in 150
when no other fetal anatomical anomalies were seen by ultrasound. Conversely, the risk was 1 in 3 if
any other anomaly was detected. They concluded that it was advisable to regard these cysts as an
indication for detailed ultrasound assessment, rather than invasive testing.

Thorax
Fetal lungs are usually visualized by midpregnancy. There are a variety of thoracic
malformations that can develop. Some of the more common include pulmonary hypoplasia, cystic
adenomatoid malformation, and pulmonary sequestration (Crane and colleagues, 1994; Gonçalves and
associates, 1994). Recent data from Treadwell and associates (1996) support a better prognosis than
previously reported.
CARDIAC EVALUATION
The four-chamber view of the fetal heart is obtained from a near transverse midchest scan plane
at the level of the heart (Fig. 10). A normal four-chamber view with symmetry and synchronous action
of the ventricles excludes 95% of clinically significant cardiac malformations.48 The normal fetal heart
is angled at 45 ± 10ˇ (1 standard deviation) to the left of the anteroposterior midline.49 The
anteroposterior midline passes through the left atrium and the right ventricle. Asymmetry in chamber
size, defects in the septum, or displacement of the fetal heart should lead to referral for a more detailed
ultrasonographic evaluation (Fig. 11).

Cardiac Evaluation. Congenital heart disease has been the most commonly recognized birth
defect with a reported frequency of 8 per 1000 live births and 27 to 77 per 1000 stillborns (Hoffman
and Christianson, 1978; Mitchell and associates, 1971). The reported frequency of specific heart
defects varies significantly between studies done on live borns, stillborns, and fetuses in whom heart
lesions were identified in utero (Chap. 47 ). Perone (1988) recommends that women with any of the
following risk factors undergo a detailed ultrasound examination of the fetal heart: nonimmune
hydrops, suspected abnormality seen by screening sonogram, teratogen exposure, parental or sibling
heart defects, aneuploidy, extracardiac anomalies, maternal diabetes, and fetal arrhythmias. The
recurrence risk for congenital heart defects if siblings or parents are affected is shown in Table 39–9.
Congenital heart defects are frequently associated with aneuploidy, and Copel and co-workers
(1988a) reported that 11 of 34 fetuses (32 percent) with cardiac anomalies detected prenatally had an
abnormal karyotype. Additionally, associated extracardiac structural abnormalities are present in 25 to
45 percent of such fetuses (Copel and associates, 1986).
Although heart motion can be visualized sonographically in a 6- to 7-week embryo, detailed
cardiac evaluation is usually not possible until at least 18 weeks. Even at this time, adequate anatomical
cardiac assessment is dependent on factors that include fetal position and activity, maternal size, and
amnionic fluid volume. The detail of such examinations depends on the availability of proper
equipment and expertise, and the study may be time consuming and require pediatric cardiological
collaboration.
Visualization of a four-chamber view is central to fetal cardiac assessment (Fig. 44–8 ). This
view is obtained by imaging a transverse plane through the fetal thorax at a level just above the
diaphragm, and allows evaluation of the size, location, and orientation of the fetal heart. Additionally,
the atrial and ventricular chambers can be assessed, the interatrial and interventricular septa viewed,
and the atrioventricular valves observed. Normally, the two atria are similar in size as are the two
ventricles. The apex of the heart typically forms a 45-degree angle with the left anterior chest wall.
The importance of the four-chamber view was demonstrated by Copel and colleagues (1987),
who reported that 71 of 74 fetuses (96 percent) with sono-graphically detectable heart defects had
abnormal four-chamber views. As reviewed by Perone (1988), at times other cross-sectional views may
be required, either to demonstrate fetal heart integrity or to characterize abnormalities. In addition to
these, M-mode echocardiography may be required to measure chamber size, wall thickness, and wall
and valve motion, and to facilitate assessment of cardiac arrhythmias (DeVore and co-workers, 1987).
Pulse Doppler and real-time Doppler color-flow mapping are also used to define normal or abnormal

39
blood flow in the fetal cardiovascular system (DeVore and associates, 1987; Shenker and colleagues,
1988).
Given these technological considerations, what accuracy should be expected of an ultrasound
examination to detect fetal cardiac disease? Crawford and colleagues (1988) reported their experiences
with almost 1000 women at high risk for having children with cardiac abnormalities. They performed
over 1750 fetal echocardiograms and successfully identified 74 of 91 anomalies (80 percent). In almost
half of those with cardiac anomalies, chromosomal or extracardiac structural defects were also found.
They emphasized that heart disease diagnosed prenatally is usually severe and is associated with a poor
long-term prognosis. By contrast, Benacerraf and associates (1987) studied a group of women who
underwent ultrasonic studies for multiple reasons. Although 49 fetuses were subsequently found to
have 66 cardiac defects, only 33 (50 percent) of these were detected antenatally. According to both of
these reports, ventricular septal defects, anomalous pulmonary venous return, and aortic or pulmonic
stenosis were especially likely to be missed by fetal ultrasound evaluation. Ott (1995) recently reported
a 14-percent sensitivity for detection of congenital heart disease in a low-risk population, compared
with 63 percent in the high-risk group. Lanouette and co-workers (1996) correctly emphasized that
routine cardiac views are not consistently available for each routine ultrasound examination. They
calculated the adjusted positive predictive value to be about 55 percent. Berghella and associates
(1996) found that significantly more lesions were detected when a pediatric cardiologist participated in
the evaluation.
CONGENITAL HEART DISEASE

The frequency of congenital heart disease (CHD) is approximately 6 to 8 per 1000 newborns,
and the recurrence risk is 8%. In 25% of cases, the etiology can be related to familial, chromosomal, or
environmental causes (Table 9).15 The prenatal risk factors for CHD are shown in Table 10.16 The
overall survival rate of fetuses with CHD remains poor (17% to 24%).17, 18
The examination of the fetal heart includes evaluation of many views, including the four
chambers, the parasagittal view (also known as the left ventricular outflow tract), the short axis, the
great vessels, and the aortic arch.

THE FOUR-CHAMBER VIEW

The structures that can be visualized in the four-chamber view are as follows:

1.Both ventricles, including the position or' the heart in the chest and the appearance of the
pericardial and pulmonary areas
2.The interventricular septum (IVS)
3.The atrioventricular valves
4.The septum primum and secundum (Fig. 2).

The ultrasonographer should obtain a number of views of the four chambers to gain adequate
visualization of all these structures (Fig. 3).

THE VENTRICLES. Although both ventricles should be similar in thickness and size, the right
ventricle is normally characterized by the appearance of the moderator band, which consists of
thickened trabeculae extending from the septum to the parietal wall of the right ventricle (see Fig. 3A).
Absence of the moderator band from its normal location implies corrected or L-transposition of the
great arteries. In this abnormality, the right ventricle functions as the left chamber, assuming the role of
pumping blood into the aorta. Thus, in contrast to D-transposition, L-transposition allows blood flow to
the lungs and body to be maintained normally.
Hyperechogenicity or thickness of the ventricular walls or ventricular septum, or both, is
consistent with cardiomyopathy (Fig. 4).
In dextroversion, the apex of the heart points to the right side of the chest. The main
differential diagnoses of this condition are cystic adenomatoid malformation of the lungs,
diaphragmatic hernia, and polysplenia. In levoversion the apex of the heart points to left side of the

40
chest excessively; the main differential diagnosis of this condition includes left pulmonary hypoplasia
and a right-sided pulmonary mass.

THE INTERVENTRICULAR SEPTUM. Defects in the IVS constitute the most common form
of congenital heart disease and can occur in various locations within the septum. Ultrasonic
visualization of small ventricular septal defects, regardless of location, may not be possible in the four-
chamber plane. For example, membranous or perimembranous defects (located adjacent to the aortic
valve) are situated below the anterior portion of the IVS and are not visualized in the four-chamber
plane (Fig. 5). Such defects usually are depicted in the parasagittal plane (Fig. 6).

THE ATRIOVENTRICULAR VALVES. The septal insertion of the tricuspid valve should be
visualized slightly below that of the mitral valve (see Fig. 2 and Fig. 3). If the insertion is lower,
Ebstein anomaly should be considered. Interestingly, hyperechogenicity limited to the area of the mitral
valve is usually inconsequential; that is, cardiomyopathy is not a consideration.

THE SEPTUM PRIMUM AND SECUNDUM. The foramen ovale is the opening between both
atrial septi, allowing blood to flow from the right atrium to the left. In endocardial cushion defect, a
single common atrioventricular valve is noted superior to a large ventricular septal defect.

DIAGNOSTIC UTILITY OF THE FOUR-CHAMBER VIEW

Because the four-chamber view depicts so many cardiac structures and is also the plane used
to evaluate cardiac arrhythmia, it is included in all obstetric studies. Copel and associates19 showed
that 92% of cardiac defects may be discovered by some abnormality in the four-chamber view and
proposed routine screening for CHD. After including the four-chamber view in their examinations,
Vergani and colleagues20 improved their CHD diagnosis sensitivity from 43% to 81%. Subsequently,
Sharland and Allan21 showed that after routinely including the four-chamber view in obstetric studies,
53 fetuses were referred for possible CHD over a period of 32 months; previously, from 1980 to 1988,
only 8 fetuses had been referred. They reported a 77% sensitivity for the four-chamber view in the
diagnosis of CHD. Studies by Bromley and co-workers22 and Wigton and associates,23 however,
suggest that the sensitivity of the four-chamber view in detecting CHD is even lower, ranging from
69% to 39%, respectively. This is understandable because the four-chamber view does not allow for
assessment of the pulmonary and aortic arteries-outflow tracts that are evaluated best in the
parasagittal, short axis, and great vessel views.

PARASAGITAL VIEW

The parasagittal view encompasses the left ventricle. aortic outflow, a portion of the right
ventricle, and the left atrium (see Fig. 6). This plane is significant for two main reasons:

1.The aorta at the level of the aortic valve can be readily assessed.
2.Membranous IVS defects (located adjacent to the aortic outflow tract and below the plane of
the four chamber view) stand a better chance of being visualized in this view.

SHORT AXIS VIEW

The short axis view (Fig. 7) encompasses the aortic and pulmonary valves as well as the
ductus arteriosus and the right branch of the pulmonary artery. It is used to evaluate the size of the aorta
and pulmonary arteries at the valvular level.

GREAT VESSEL VIEW

41
 The great vessel view depicts the relatively parallel relationship of the superior vena cava,
aorta, and pulmonary arteries after the latter two cross each other (Fig. 8). Clear visualization of this
plane indicates that the crossing of the aorta and pulmonary artery is normal and virtually rules out
transposition of the great vessels. Aortic or pulmonary stenosis also can be recognized in this view.
In truncus arteriosus, the pulmonary artery is not clearly depicted by ultrasound. Instead, the
aortic outflow tract is large and the aorta is overriding.
The great vessel view also allows a comparative measurement of the two arteries a short
distance beyond the valvular level; the measurements should be obtained from the inner aspects of
these arteries. Normally the ratio of pulmonary artery: aorta has a mean value of 1.09 (range = 0.75 to
1.43) and is independent of gestational age.24

AORTIC ARCH

The aortic arch is depicted in Figure 9. Coarctation of the aorta most frequently occurs at the
isthmus, the area of the arch at the insertion site of the ductus arteriosus. The isthmus is normally
narrow in the fetus but dilates in the newborn after the ductus closes. Because narrowing in the isthmus
occurs normally, in utero diagnosis of coarctation of the aorta is difficult.

ESOPHAGEAL ATRESIA

This is a very rare anomaly occurring at a rate of 1:25,000 births. In 10% of cases it can be
characterized ultrasonographically by a dilated proximal esophagus, absence of stomach echo, and
polyhydramnios.25 In the remaining 90% of cases, however, the defect cannot be ultrasonically
recognized because of abnormal communication channels between the proximal aspects of the
esophagus, trachea, and stomach, which result in free flow of amniotic fluid.

PULMONARY CYSTIC ADENOMATOID MALFORMATION

Three types of pulmonary cystic adenomatoid malformation have been characterized26:

Type I: The cysts are large ( 2 cm). The prognosis depends on the size of the tumor and the
degree of fetal hydrops (Fig. 10). If the fetus survives, resection of the affected portion of the lung is
usually indicated.
Type II: The cysts are less than 1 cm in diameter, but other anomalies of the renal or
gastrointestinal tract may be present.
Type III: The lesion is microcystic, brightly echogenic, and large, and its presence is
associated with a poor prognosis (see Fig. 10).

A pulmonary cystic adenomatoid malformation can result in a right or left shift of the
mediastinum (see Fig. 10). The differential diagnosis includes pulmonary sequestration and
diaphragmatic hernia.27

PULMONARY HYPOPLASIA

Pulmonary hypoplasia is associated with a high mortality rate. Lung weight at autopsy is 2
SD below the mean.49 The etiology of this disease usually is related to (1) compression of the lungs,
and (2) oligohydramnios28 (Table 11); however, the disease also can occur as a primary condition.
Although high-resolution equipment has enabled lung tissue to be visualized adjacent to the
heart, most studies dealing with antenatal diagnosis of pulmonary hypoplasia have focused on reduced
chest size as a predictor for the condition.29, 30 More recently, Vintzileos and colleagues31 showed
that the highest sensitivity (85%) and positive predictive value (83%) for the diagnosis of pulmonary
hypoplasia could be obtained with the following ratio:

42
 [chest area - heart area/chest area] x 100

The chest area should be traced at the midpoint of the chest wall. The ratio is independent of
gestational age and is considered abnormal when it is less than or equal to 62 (5th percentile). The ratio
can be used when the abdominal circumference is large (as in ascites or obstructive uropathy) or small
(as in omphalocele). It is not applicable to fetuses with diaphragmatic hernia because chest size is
artificially enlarged in this condition.

DIAPHRAGMATIC HERNIA
Congenital diaphragmatic hernia results from incomplete fusion of the pleuroperitoneal
membrane, occurs more frequently on the left, and has a frequency of 1 in 2000 to 3000 births (Romero
and associates, 1988). On ultrasound examination, a cystic structure, usually behind the left atrium, is
seen on an axial image at the level of the four-chamber cardiac view. Associated findings include
absence of an intra-abdominal stomach bubble, a mediastinal shift usually with a normal cardiac axis,
and a small abdominal circumference. The most specific finding is peristalsis in the fetal chest.
Associated hydramnios also is common and was identified in 75 percent of affected fetuses studied by
Adzick and co-workers (1985).
Diaphragmatic hernia is associated with other major anomalies in almost half of all cases, and
chromosomal abnormalities are found in up to 20 percent of affected infants (Benacerraf and Adzick,
1987; Romero and associates, 1988). Importantly, Benacerraf and Adzick (1987) reported an overall
survival rate of only 10 percent despite accurate prenatal diagnosis and optimal neonatal management
in a tertiary-care hospital. Adzick and co-workers (1985) found that survival is related to defect size,
and noted that nonsurvivors may have more abdominal viscera displaced into the chest earlier in
gestation. They also reported that survival was 55 percent when there was normal amnionic fluid
volume, compared with 10 percent when hydramnios was present. Neonatal death generally results
from respiratory failure secondary to pulmonary hypoplasia or from associated lethal anomalies. Moya
and colleagues (1996) have documented decreased surfactant components in amnionic fluid. Although
diaphragmatic hernias are usually repaired after delivery, Harrison and associates (1990) have
attempted repair in utero.

Congenital defects in the diaphragm result in herniation of bowel, stomach, and possibly parts
of the liver and pancreas, into the chest. The hernia displaces the heart and mediastinum, making
antenatal diagnosis possible. The most common defect (1:3000 births) involves the foramen of
Bochdalek, which is situated in the posterolateral aspect of the diaphragm.32 This condition may be
associated with cardiac abnormalities or aneuploidy (trisomy 13, 18, and 21).
In utero corrective surgery is possible in cases of isolated diaphragmatic hernia. The outcome
of open in utero surgery, however, should be weighed against that of extracorporeal oxygen membrane
oxygenation in the neonate, which has been reported to carry a success rate of only 55%. Data on this
subject are still evolving.33
Another rare type of diaphragmatic hernia is found through the foramen of Morgagni. This
hernia is associated with a poor prognosis because of its association with other anomalies, such as
hydrocephalus, encephalocele, enlarged cisterna magna, malrotation of the gut, cardiac anomalies, and
trisomies.32
The differential diagnosis of diaphragmatic hernia includes (1) eventration or displacement of
visceral contents into the chest secondary to a thin diaphragm; (2) chest mass; and (3) pulmonary
tumor.

Abdomen
ABDOMINAL WALL DEFECTS
Anterior abdominal wall defects as a group are relatively common malformations. The two most
common are omphalocele and gastroschisis, and each has a frequency of approximately 1 in 5000 live
births. Because of maternal serum alpha-fetoprotein screening programs, these two defects can be
ascertained early in pregnancy. Although these defects have many similarities, it is important to

43
recognize that they differ markedly in developmental pathology, association with other major
abnormalities, and prognosis. These are discussed in detail in Chapter 39.

Fetal bowel normally is located outside the abdomen in the first trimester of pregnancy. This is
known as physiologic herniation, a condition that can be appreciated with the use of high-frequency
vaginal transducers.34, 35 Thus, the diagnosis of omphalocele should not be made before the 14th
week of pregnancy.
True ventral wall defects occur at a rate of 1:2500 births. Two main forms are described:
omphalocele and gastroschisis. In omphalocele, the fetal gut (and sometimes the liver) is outside the
abdomen but is covered by a sac-like cyst interface (Fig. 11). In gastroschisis, segments of intestine are
noted in the peritoneal cavity without any sac-like cover. In contrast to omphalocele, the umbilical cord
in gastroschisis is inserted into the abdominal wall (see Fig. 11). Gastroschisis is not associated with
other fetal abnormalities, but a chromosomal abnormality may be found in approximately 50% of
fetuses with omphalocele, particularly if fetal liver is not part of the hernia.36, 37 Other anomalies
involving the cardiac, skeletal, renal, and central nervous systems may also be present. The Beckwith-
Weidman syndrome of organomegaly and hypoglycemia has been described in association with
omphalocele.
In the presence of a ventral wall defect, the mode of delivery (vaginal delivery vs cesarean
section) remains controversial.38, 39 Vaginal delivery appears safe, however, when the hernia is small
and the liver is not herniated.

GASTROINTESTINAL ABNORMALITIES
Using high-resolution diagnostic sonography, the integrity of the abdominal wall, umbilical cord
insertion, and intraabdominal anomalies can be assessed with confidence (Fig. 44–9 ). The liver,
spleen, gallbladder, and bowel can be identified in most pregnancies. Normally, the appearance of the
fetal bowel changes with gestational age, and considerable overlap exists between normal and
pathological conditions (Hertzberg, 1994). Pretorius and colleagues (1988) reported successfully
visualizing the fetal stomach in 98 percent of fetuses after 14 weeks. Moreover, nonvisualization was
associated with an abnormal outcome in 55 percent of fetuses studied after 14 weeks and 100 percent
after 19 weeks. They suggested repeat sonograms for all cases of stomach nonvisualization.

The fetal stomach can be seen as a fluid-filled structure on the left side of the abdomen caudal to
the four-chamber view (see Fig. 5). The normal umbilical cord insertion can be seen in a transverse
section below the fetal stomach (Fig. 12). In this area, ventral wall defects of the fetus are seen,
including gastroschisis and omphalocele. Gastroschisis is an open defect in the abdominal wall with
evisceration of the abdominal organs that usually occurs to the right of a normal cord insertion. There is
no membrane covering the eviscerated fetal bowel loops, which can be seen in the amniotic fluid at the
site of the defect (Fig. 13). Omphalocele, a failure of the embryonic gut to return into the abdomen by
12 weeks' gestation, occurs at the cord insertion (Fig. 14) and usually is covered by a membrane
consisting of peritoneum and amnion.50 Omphalocele is associated with fetal chromosome
abnormalities in one third to one half of cases51 and should prompt a careful search for other fetal
anomalies. IUGR commonly is associated with both gastroschisis and omphalocele.
The "double-bubble" sign, classically associated with duodenal obstruction, is not specific for
atresia but also may be seen with obstruction from malrotation or an annular pancreas.
OBSTRUCTIVE GASTROINTESTINAL LESIONS AND HYPERECHOGENIC
BOWEL

Duodenal atresia results from failure of recanalization of the upper gastrointestinal tract at 8
weeks' gestation. It may be associated with Down syndrome and other anomalies involving the
gastrointestinal. cardiac, and renal systems. This condition is characterized by dilation of the stomach
and proximal part of the duodenum (double-bubble sign). Occasionally the diagnosis can be made
before the 20th week of pregnancy, but it is more likely to be made after the 20th week, when the
quantity of swallowed amniotic fluid exceeds the resorptive capacity of the gut.40

44
 Small bowel obstruction results from in utero avascular necrosis of segments of jejunum and
ileum. Dilation of small bowel proximal to the necrotic segments is ultrasonically recognizable by the
presence of valvular flaps projecting into the lumen.
The pattern of bowel dilation in other obstructive bowel abnormalities is not specific enough
to allow for a precise diagnosis. These abnormalities include malrotation of the bowel, volvulus,
intussusception, and Hirschprung disease (congenital intestinal aganglionosis).
Meconium within normal bowel sometimes appears bright and has been described as
hyperechogenic bowel (Fig. 12). In many fetuses that exhibit this entity, the outcome may be
norma141; however, it has been associated with cystic fibrosis and aneuploidy.42 Prospective couples
should be counseled regarding appropriate antenatal testing.
Differentiation between hyperechogenic bowel and meconium peritonitis may be possible. In
the latter condition, bowel perforation results in extravasation of meconium into the abdominal cavity.
Meconium induces an inflammatory response, formation of adhesions, and calcium deposition in the
area.

GASTROINTESTINAL ATRESIA
Gastrointestinal Atresia. Most of these anomalies are caused by obstruction with subsequent
proximal bowel dilatation. In general, the more proximal the obstruction, the more likely it will be
associated with hydramnios. Esophageal atresia is one of the most common gastrointestinal
anomalies, and is encountered in about 1 in 3000 births (Robertson and colleagues, 1994). Most cases
are associated with a tracheoesophageal fistula and they cannot be diagnosed reliably in utero,
although they may be suspected when hydramnios is found in the absence of a fluid-filled stomach.
About half of fetuses have associated anomalies and cardiac malformations are most common.
Pretorius and colleagues (1987), in a retrospective review, reported that only 7 of 22 infants born with a
tracheoesophageal fistula had both hydramnios and a nonvisualizing stomach. In an additional seven
pregnancies, hydramnios and a fetal stomach were both present sonographically. None of these women
developed hydramnios before 24 weeks, and other abnormalities were present in 12 of the 22 infants.
Duodenal atresia occurs in about 1 in 10,000 live births (Robertson and colleagues, 1994). The
lesion is diagnosed prenatally by the demonstration of the double-bubble sign, which represents the
distention of the stomach and the first part of the duodenum (Fig. 44–10 ). Demonstrating continuity
between these two structures will differentiate duodenal atresia from other cystic structures in the upper
abdomen. The diagnosis of duodenal atresia generally is not possible before 24 weeks, although it has
been made as early as 19 weeks (Romero and associates, 1988). More than half of fetuses have
associated anomalies and trisomy 21 is encountered in approximately 30 percent of infants.
Obstructions in the lower small bowel usually result in multiple dilated loops, and these may show
increased peristaltic activity. Large bowel obstructions and anal atresia are less readily diagnosed in
utero because hydramnios is not a typical feature and the bowel may not be significantly dilated.

Evaluation of Abnormal a-Fetoprotein Testing

For more than a decade, a-fetoprotein (AFP) testing has been offered to obstetric patients in the
United States. Many practitioners are now using the triple screen, which includes AFP, hCG, and serum
estriol. These biochemical markers are used as a screening test for fetal anatomic abnormalities and
Down syndrome. Fetal abnormalities associated with elevated AFP levels include fetal death, spina
bifida, anencephaly, abdominal wall defects such as omphalocele and gastroschisis, and renal
abnormalities. Low AFP levels have been associated with Down syndrome and other chromosomal
abnormalities. Because AFP levels and the other biochemical markers vary with gestational age, the
interpretation of these tests demands accurate clinical dating. The first step in evaluation of a patient
with abnormal serum AFP levels is ultrasound.
Because maternal serum AFP levels normally increase with advancing gestational age, an
apparent elevation might result from an error in dates. Twins also cause an elevation of AFP levels. In a
basic ultrasound examination to evaluate elevated maternal serum AFP levels, as many as one third of
patients are shown to have incorrect dates, multiple gestation, or fetal death. If the dates are correct and
the elevated maternal serum AFP level is confirmed, referral for a high-detail ultrasound examination is
appropriate. This should be performed by a sonologist with experience in diagnosing fetal anomalies by
ultrasound. Detection of these anomalies is discussed later in the sections on clinical applications.

45
 In patients who have elevated AFP levels and normal high-detail ultrasound examinations,
determination must be made about whether amniocentesis is appropriate. The information from the
ultrasound can then be used when counseling the patient. In the past, amniocentesis was recommended
for determination of amniotic fluid AFP and karyotype. High-detail ultrasound now can detect up to
95% of neural tube defects, so the risk of missing spina bifida is low. It is appropriate to inform the
patient regarding the risk of an invasive procedure such as amniocentesis as well as about the very low
risk of a normal high-detail ultrasound missing spina bifida.20
In patients who have low AFP levels or abnormal triple-screen results, ultrasound can play an
important role in interpretation and diagnosis.21 An inaccurate gestational age may explain up to half
of cases of apparently low maternal serum AFP values. Usually, if the ultrasound gestational age is
within 2 weeks of that determined by the last menstrual period, the gestational age used for
interpretation should not be changed. Ultrasound is less accurate for determination of chromosomal
abnormalities, such as Down syndrome, than it is for determination of neural tube defects. Benacerraf
and colleagues22 reported the finding of occipital nuchal skin thickening in about half of fetuses with
trisomy 21; these data subsequently were confirmed by other investigators.23 Other abnormalities seen
with increased incidence in fetuses with Down syndrome include short femurs, short humeri, dilation of
the fetal renal pelvis, hydrocephalus, and fetal cardiac abnormalities. Combining multiple minor
dysmorphic features into an aneuploidy scoring system may prove useful both in the detection of
abnormal fetuses and in the reduction of risk.

Genitourinary Tract
Using transabdominal sonography, the fetal kidneys are visualized as paraspinous masses
frequently as early as 14 weeks, and routinely by 18 weeks (Patten and co-workers, 1990). Normal
kidneys appear elliptical in parasagittal planes (Fig. 44–11 ) and circular in transverse planes (Fig. 44–
12 ). Initially, fetal kidneys are uniformly hypoechoic; however, as pregnancy advances, more detail is
visualized. The renal cortex, which is echogenic, surrounds the hypoechoic medullary pyramids and is
outlined by perinephric fat and the renal capsule. The renal pelvis is centrally located and anechoic.
Nomograms have been developed that describe fetal kidney dimensions throughout pregnancy
(Grannum and colleagues, 1980; Sagi and associates, 1987). Although kidney length increases linearly
throughout pregnancy, the ratio of kidney circumference, measured in a transverse plane, to the
corresponding abdominal circumference remains constant between 0.28 and 0.30. In addition, the
anterior-posterior (AP) dimension of the renal pelvis should be less than half the A-P dimension of the
entire kidney A-P dimension.
Urine production normally begins late in the first trimester, and consequently the fetal bladder
can be observed as an anechoic area in the pelvis early in the second trimester. Fetal urine production
increases from 5 mL/hr at 20 weeks to about 50 mL/hr at 40 weeks (Rabinowitz and co-workers, 1989).
In the normal fetus, the bladder fills and empties every 20 to 45 minutes.
Assessment of amnionic fluid volume provides important information regarding fetal renal
function. Often, significant fetal urinary tract abnormalities result in oligohydramnios (Chap. 29 ).
Conversely, normal amnionic fluid volume suggests urinary tract patency with at least one functioning
kidney, especially in the second half of pregnancy when fetal urine is an increasingly important
component of the amnionic fluid. Sivit and colleagues (1986) reported 16 women identified to have
severe oligohydramnios between 16 and 30 weeks. When studied after pregnancy termination or
delivery, 10 of these infants had urinary tract anomalies. Before 16 to 20 weeks, there may be normal
amnionic fluid volume despite absent renal function, although otherwise unexplained oligohydramnios
still suggests a urinary abnormality.
There have been at least three large prospective antenatal sonographic screening programs from
which the frequency and type of fetal urinary tract abnormalities can be ascertained. Helin and Persson
(1986) performed 24,000 ultrasound examinations in nearly 12,000 women at 17 and again at 33
weeks. They identified urinary tract anomalies in 33 fetuses (0.27 percent), and were able to confirm an
abnormality in 23 neonates. Only 3 of 33 anomalies were detected at 17 weeks, and the remainder were
identified at 33 weeks. By contrast, Livera and co-workers (1989) performed sonograms on nearly
6300 women at 28 weeks and diagnosed fetal renal abnormalities in 92 (1.5 percent). Postnatal studies
confirmed abnormalities in 42 neonates, and 13 had bilateral disease. There were 4 perinatal deaths,
and all of these had bilateral disease. Seven infants (0.11 percent) thought to be normal as assessed by
fetal sonography were diagnosed to have renal abnormalities after they developed urinary infections

46
during the first year of life. Some of the neonatal abnormalities reported in these two studies are listed
in Table 44–7.
Gunn and co-workers (1995) prospectively screened nearly 17,000 consecutive women at 16 to
18 weeks over a 5-year period. Of these, 3856 fetuses were again examined after 28 weeks for
obstetrical indications. Renal tract anomalies were identified in 313 (8 percent) and in 55 (1.4 percent),
these were significant. Upper urinary tract dilation was most commonly encountered (298 cases), but it
was transient in two thirds of cases. Follow-up of infants with transient obstruction showed that only 1
developed urinary infections. Other abnormalities included obstruction in 23 infants and 15 of these
required surgical correction. Finally, 8 infants had unilateral multicystic renal dysplasia and 3 others
had posterior urethral valves.
Callan and colleagues (1990) reported findings from 55 fetuses identified to have genitourinary
abnormalities in women referred to Johns Hopkins Hospital for ultrasound evaluation. More than half
(57 percent) of these fetuses had bilateral involvement. They undertook no interventional therapy in
utero, and there were 35 survivors (66 percent), of whom 22 underwent surgical therapy postnatally.
Factors that portended a poorer prognosis were bilateral disease, oligohydramnios, and associated
anomalies.

The frequency of urinary abnormalities is approximately 7:1000 newborns, and the recurrence
risk is 8% to 10%.
The etiology of urinary tract abnormalities should extend beyond the apparent site of the
lesion. For example, dilation of the ureteropelvic junction (UPJ) may result either from obstruction at
the upper ureter or from pathology at a more caudad level. This includes increased intraluminal
pressure secondary to reflux at the level of the vesicoureteral junction resulting in dilation of the UPJ.
Similarly, a posterior urethral valve (PUV) will dilate the UPJ and even produce hydronephrosis. Thus,
in discussing urinary tract abnormalities, it is reasonable to start with the urethra and proceed cephalad.

OBSTRUCTIVE UROPATHY
Fetal urinary tract obstruction may develop at the ureteropelvic junction, the ureterovesical
junction, or at the urethra. The severity and location of the obstruction can be determined by assessing
amnionic fluid volume as well as the distribution of any resulting urinary tract dilatation. As a general
rule, fetal ureters are not visualized, and thus their identification indicates hydroureter. By contrast,
after 20 weeks the fetal renal pelves may normally have an anteroposterior diameter of up to 10 mm.
The normal ratio of the anteroposterior renal pelvis diameter and kidney diameter measured in a
transverse plane is less than 50 percent (Arger and co-workers, 1985).
Brown and colleagues (1987) described 142 neo-nates evaluated for hydronephrosis over 6
years and reported that 110 were first identified by antenatal sonography. Of the fetuses diagnosed with
hydronephrosis, almost 50 percent had ureteropelvic junction obstruction, 25 percent distal ureteral
obstruction, 15 percent duplication of the collecting system, and 5 percent had a posterior urethral
valve. Ghidini and cohorts (1990) reported results from 70 fetuses with ureteropelvic junction
obstruction. Those with renal pelvis dilatation less than 1 cm uniformly did well, whereas those with
dilatation more than 2 cm required postnatal pyeloplasty in three fourths of the cases. Those with
dilatation of 1 to 2 cm—about half of the total—did well if the findings were bilateral; conversely,
about 10 percent with unilateral dilatation of this magnitude eventually required pyeloplasty.
Obstructive uropathy may be caused by posterior urethral valves, urethral atresia, or persistent
cloaca syndrome. Ultrasound findings include a large bladder and enlarged ureters, which are seen as
cystic convoluted structures in the lower abdomen (Fig. 16). Ureteropelvic junction obstruction is
suspected when an enlarged fetal renal pelvis, without an enlarged bladder, is seen.

POSTERIOR URETHRAL VALVE

Most PUVs are partial, such that the resulting bladder dilation is not severe. The ureters may
only be slightly dilated, and if present, hydronephrosis is moderate (Fig. 13). In the severe form,
however, the pathophysiology is severe and may resemble the findings in agenesis of the urethra. In
complete PUV, the bladder is markedly dilated. The ureters also are convoluted and large.

47
Hydronephrosis is severe. Oligohydramnios prevents appropriate pulmonary development and leads to
pulmonary hypoplasia.
Early treatment of this condition (less than 20 weeks' gestation) is important to prevent
permanent renal damage. The indications for therapy include the following:

1.Early diagnosis (18 to 20 weeks' gestation)

2.A fetal urine sample showing sodium concentrations less than 100 mg/dL, chloride < 90
mg/dL, and osmolality, 210 mOsm/dL—all indirectly pointing to the ability of the kidneys to provide
the function of salt conservation
3.Decreasing amniotic fluid volume but not frank oligohydramnios

A number of treatment options are available:

1.Open fetal surgery to marsupialize the bladder

2.A two-ended curved catheter to drain urine into the amniotic cavity (catheter insertion has
been difficult, however, and is frequently followed by catheter displacement and blockage)
3.Frequent bladder drainage procedures.43

To prevent pulmonary hypoplasia, treatment should be initiated by the 20th pregnancy week,
Although early treatment may prevent development of pulmonary hypoplasia, however, 30% to 50% of
these children may subsequently develop dysplastic kidneys and require renal transplantation.44

RENAL DISORDERS.
The fetal kidneys can be seen on a transverse scan plane just below the level of the stomach, in
the dorsal paraspinal areas (Fig. 15). The fetal bladder is seen as a round, fluid-filled structure in the
anterior midline of the fetal pelvis. The amniotic fluid volume provides a clue to fetal renal function. In
the fetus with absent kidneys, renal obstruction, or nonfunctioning kidneys (renal dysplasia) after 20
weeks' gestation, the amniotic fluid volume is markedly decreased. Before 20 weeks' gestation,
however, the amniotic fluid volume may be normal despite renal malformations.

HYDRONEPHROSIS

Dilation of the renal calyceal system results from abnormalities at a lower level of the urinary
tract. It is differentiated from multicystic dysplastic disease by (1) ultrasonic visualization of radially
placed calyces communicating with the renal pelvis and (2) preservation of some renocortical tissue
(Fig. 16).
In utero diagnosis of pyelectasis, UPJ dilation, and hydronephrosis is significant because it
identifies fetuses who will require postnatal urologic evaluation. As a result, early surgical intervention
or medical treatment with antibiotics will prevent irreversible renal compromise.

RENAL AGENESIS
Bilateral renal agenesis has an incidence of about 1 in 4000 births. No kidneys will be visualized
sonographically at any point during gestation. Because there is no urine production, severe
oligohydramnios ultimately develops. In this situation, the fetal adrenal glands appear to enlarge, and
care must be taken to avoid mistaking them for kidneys. Death invariably follows, either in utero or
shortly after birth, and the infant exhibits pulmonary hypoplasia, limb deformities, loose skin, and
typical facies of the Potter syndrome. Associated anomalies, especially cardiac, are common (Chap.
29 ).

The frequency of this condition is 1:4000 births, and the risk of recurrence is 3%.51 The
etiology is variable and may include chromosomal or genetic disorders (recessive or dominant mode of
inheritance). It may also be part of the VATER association: vertebral defects, anal atresia,

48
tracheoesophageal fistula, and radial and renal dysplasia. The outcome of fetuses with renal agenesis is
poor because of oligohydramnios and associated pulmonary hypoplasia.
Intravenous administration of furosemide (40 mg IV) has not been helpful in differentiating
renal agenesis from severe intrauterine growth restriction. Further, because of associated
oligohydramnios as well as an enlarged adrenal gland that mimics renal appearance, the diagnosis by
gray scale ultrasound is difficult (sensitivity, 50%).51 In suspected cases, however, the use of color
Doppler velocimetry may show absence of renal arteries in bilateral renal agenesis and only one renal
artery in the unilateral form of this abnormality (Fig. 17).52

CYSTIC RENAL DISEASE

Cystic renal disease is a complex subject because cystic changes of the kidneys may be present
secondary to multiple etiologies including hereditary diseases (autosomal recessive infantile polycystic
kidneys, autosomal dominant adult polycystic kidneys), dysmorphology (multicystic dysplastic kidney,
multilocular cystic nephroma), or chronic obstructive uropathy (Potter type II). Antenatal
differentiation of the underlying etiology of cystic changes is problematic.
Of the hereditary polycystic diseases, autosomal recessive infantile polycystic kidneys may be
seen antenatally, while the autosomal dominant condition usually becomes manifest in adulthood and
would not be expected to be seen antenatally. Autosomal recessive infantile polycystic kidney disease
may present with large, solid-appearing kidneys, a large abdominal circumference, and severe
oligohydramnios. The “polycystic” changes of these kidneys can only be identified microscopically.
Cystic kidneys secondary to dysmorphology such as multicystic dysplastic kidney have been
diagnosed antenatally. The typical sonographic appearance is multiple peripheral cysts, with a
relatively normal-sized renal pelvis. Differentiating this entity from cystic changes secondary to
obstructive uropathy is a challenge.
Most important in discussing renal cystic changes is the determination of whether findings are
unilateral or bilateral and assessment of amnionic fluid. Prognosis is good if findings are unilateral and
amnionic fluid volume is normal, while a bad prognosis secondary to pulmonary hypoplasia may be
anticipated if there is severe oligohydramnios and bilateral involvement.

INFANTILE POLYCYSTIC KIDNEY DISEASE

This is an autosomal recessive disorder. The kidneys are enlarged (ratio of kidney:abdominal
circumference greater than the norm of 30%) and show small multicystic echoes.53 Unfortunately, the
diagnosis cannot always be made before 24 weeks' gestation54 because several subtypes of infantile
polycystic kidney disease exist, and these vary in onset and severity.

MULTICYSTIC-DYSPLASTIC KIDNEY DISEASE

The etiology of this condition may be secondary to a chromosomal abnormality or a mutant

gene. It is rare, occurring at a rate of 1:10,000 births, and has a male-to-female ratio of 2:1. The
condition is unilateral in 75% of cases.
The etiology is related to either (1) poor induction of nephron formation or (2) obstructive
uropathy. Defects in nephron formation occur early in embryogenesis, thus impeding renal
development. In such cases, the kidneys are very small, each weighing as little as 1 g, and cysts are
evident only via microscopic examination. This defect is classified as Potter type II-B dysplastic
kidney.55 If the defect develops by 9 to 13 postmenstrual weeks, the fetal kidney assumes a large
multicystic appearance (Potter type II-A; Fig. 18).
Megacystis-microcolon-intestinal hypoperistalsis (MMIH) syndrome is a fatal autosomal
recessive disorder believed to result from an end-organ receptor defect confined to the smooth muscle
of the urinary and gastrointestinal tracts.56, 57, 58, 59 It is characterized by a large, thick-walled
bladder plus dilation and distention of the small bowel, including the duodenum.57, 58 The kidneys
may also appear hydronephrotic or even multicystic. Amniotic fluid volume may be either normal or
excessive. The condition is differentiated from PUV by the absence of oligohydramnios and dilation of

49
the proximal urethra. This entity has been described only recently, so it is not clear whether diagnosis
by ultrasound is always possible before 24 weeks' gestation.

PRUNE-BELLY SYNDROME

In prune-belly syndrome, the bladder is dilated, the abdominal wall lax, and testicles
undescended (cryptorchidism). Although this condition may result from a PUV, it is also believed that it
may represent a primary mesoderm defect in the abdominal wall and urinary tract muscles.45
Fortunately in most cases of PUV the urethral obstruction is incomplete, allowing for fetal urination
and maintenance of near-normal amniotic fluid volume.

THE URETEROPELVIC JUNCTION

Dilation of the UPJ (Fig. 14) results from (1) abnormal recanalization of the upper part of the
ureter, resulting in varying degrees of obstruction; or (2) absence of the longitudinal muscle fibers in
the upper ureter and renal pelvis. In the latter dysfunction, there is abnormal forward propulsion of
urine, resulting in a dilation of the UPJ.46 Importantly, dilation of the UPJ may be associated with
other anomalies involving the fetal cardiac, gastrointestinal, and central nervous systems.
Further, male fetuses are more frequently affected than female (5:1). The UPJ dilation also
occurs more frequently on the left side and can be unilateral in 70% of cases.

PYELECTASIS

The etiology of a dilated renal pelvis or pyelectasis is similar to that of a dilated UPJ. Reflux
occurring at the level of the vesicoureteral valves also may result in pyelectasis (Fig. 15).
The definition of mild or minimal pyelectasis in the literature is confusing.47 Further, the
outcome of fetuses with minimal pyelectasis is not all "benign" as suggested in some studies.48 In fact,
many such fetuses may require subsequent medical or surgical intervention. Thus, an anteroposterior
diameter equal to or greater than 4 mm or 7 mm before and after 33 weeks' gestation, respectively,
warrants postnatal follow-up.48
Moreover., approximately 3.3% of fetuses with pyelectasis in the range of 3 to 5 mm may also
have chromosomal abnormalities, including Down syndrome.49, 50 Interestingly, 25% of fetuses with
Down syndrome have pyelectasis, whereas only 2.8% of fetuses with a normal karyotype show this
condition.49

Externally visible body defects and skeletal abnormalities

CLEFT LIP AND PALATE

It is now possible to image the fetal nose area and upper lip to rule out cleft lip (Fig. 28). Cleft
lip alone is genetically different from the combination of a cleft lip and palate and is more likely to
occur in female infants (sex ratio, 2:1). Importantly, both conditions may be components of genetic,
chromosomal, or other syndromes.

CYSTIC HYGROMA

Cystic hygroma is a rare (1:6000 pregnancies) disorder and usually occurs as a sporadic event,
although in some cases a recessive mode of inheritance is implicated. Importantly, 75% of cases have
an associated chromosomal abnormality, including 45,X trisomies (two thirds of cases).13, 18, 21
In this disorder, poor development of communication channels between the jugular veins and
the cervical lymph sacs (jugular lymphatic obstruction sequence) results in the formation of cystic

50
hygromas (Fig. 29). These can vary in size depending on the degree of obstruction. In some cases,
cystic hygromas have been noted to regress in utero, implying growth in the communication channels
with advancing gestational age.83 In mild cases, the differential diagnosis includes thickening of the
nuchal occipital fold secondary to aneuploidy.84 In severe cases, massive fetal hydrops develops and
intrauterine fetal death occurs in the second trimester of pregnancy.

Cystic hygromas are congenital malformations of the lymphatic system that are usually seen in
the nuchal region. They are visualized in the posterior fetal neck and are sonolucent and may be
septated. Although hygromas are associated with fetal hydrops, they commonly co-exist with
chromosomal anomalies. In first-trimester fetuses, aneuploidies predominate (Johnson and colleagues,
1993; Shulman and associates, 1992). In second—and third-trimester fetuses, monosomy XO becomes
the most commonly associated chromosomal aberration. Even with spontaneous resolution of
hygromas, aneuploidy may be present. However, in fetuses with normal karyotypes in whom there is
spontaneous resolution of the hygroma, Shulman and co-workers (1994) usually found a good
prognosis.
There is evidence that fetuses with septated lesions have a worse prognosis than those without
septations. Brumfield and colleagues (1996) described 61 fetuses with cystic hygroma and classified
them according to whether septae were seen ultrasonically. Those with septated lesions were more
likely to have an abnormal karyotype or to develop hydrops, and their survival was significantly
diminished. In either case, however, outcomes were dismal.
FETAL HYDROPS

This term is used to describe accumulation of fluid in some or all serous cavities in
conjunction with massive fetal edema. The etiology is immune in 13% of cases and nonimmune in the
remaining 87%. In the latter group, the etiology is idiopathic in 22%, extrinsic in 1% (i.e., due to
infections, such as TORCH or parvovirus B 19), and intrinsic in 64%. The most common intrinsic
causes are cystic hygroma and cardiac defects. Other intrinsic etiologies include: chromosomal
abnormality, arteriovenous shunts, twin-to-twin transfusion syndrome, fetomaternal hemorrhage,
pulmonary masses. and inherited diseases, such as -thalassemia, Tay-Sachs disease, and
hemoglobinopathy.85

SACROCOCCYGEAL TERATOMA

Sacrococcygeal tumor appears as a predominantly echogenic mass attached to the

sacrococcygeal area. It is quite rare (1:40,000 births) but has the potential to become malignant. The
size is variable, but the majority of tumors are small (Fig. 30). In approximately 10% of cases, the mass
is equal to or greater than 10 cm at term, requiring delivery by cesarean section.86

SKELETAL DYSPLASIA

Skeletal dysplasia involves a heterogeneous group of abnormalities characterized by

variability in the mode of inheritance, recurrence risk, gene penetrance, and type of limb shortening.87
It is beyond the scope of this chapter to describe each possible abnormality in detail.
In most skeletal dysplasias, the first noticeable feature is short limbs (Fig. 31). Once this is
established, a detailed survey of fetal anatomy is carried out to identify the specific dysplasia. Attention
to the following areas is helpful: (1) facial abnormality, (2) cephalic size, (3) shortened radius, (4)
segment of bone shortened, (5) small or barrel-shaped chest, (6) cardiac defects, (7) head size, (8)
protuberance of abdomen; (9) fetal edema; and (10) demineralization of bone. The abnormal ultrasound
findings in various skeletal dysplasias are listed in Table 16.

51
8. ASSESSMENT OF CHANGES IN AMNIOTIC FLUID
VOLUME
Amniotic fluid is a physiologic extension of the fetus. Abnormalities of amniotic fluid volume
are nonspecific findings that warrant further investigation. Polyhydramnios is defined as an amniotic
fluid volume in excess of 2000 mL. The clinical diagnosis is made by the findings of a large-for-date
uterine size, increased fluid, and a normal-sized fetus. The excess fluid is seen as large anechoic areas
on ultrasound. A single pocket of fluid that is 8 cm or larger suggests polyhydramnios; this occurs in
about 1% of pregnancies.52 An excess of fluid may be found in maternal diabetes, erythroblastosis, or
fetal malformation.53 In severe erythroblastosis, fetal hydrops may be seen at the time of ultrasound
study.
In one third of pregnancies complicated by polyhydramnios, no cause is determined.54 Fetal
malformations can complicate up to 40% of cases when twins, diabetes, and blood group
incompatibility are excluded.
Oligohydramnios can be associated with fetal renal abnormalities, intrauterine growth
retardation, postdate fetuses, or membrane rupture. The clinical diagnosis is made when the fundal
height is small and ultrasound examination shows little or no amniotic fluid. When amniotic fluid is
decreased, the fetal small parts are crowded, and the fetus is in contact with the uterine wall in most
scanning planes.
The amniotic fluid index, a sum of the largest vertical pocket of amniotic fluid in each of four
quadrants of the uterus, is a useful semiquantitative measurement of fluid volume.55
Severe oligohydramnios is present when the largest vertical pocket of amniotic fluid measures
less than 1 cm. Major fetal anomalies were observed in 13% of patients with severe oligohydramnios.
In the structurally normal fetus with intact membranes, severe oligohydramnios may be an indication
for delivery.56
Estimation of amnionic fluid volume using ultrasound has emerged as an important method of
fetal assessment (Chap. 29 ). Many different definitions of diminished amnionic fluid volume
(oligohydramnios) and excessive fluid (hydramnios) have been proposed, depending on the method
used to quantify the volume of fluid. Originally, Manning and co-workers (1980) proposed that a
“pocket” of fluid measuring 1 cm less in the vertical dimension signified pathological oligohydramnios.
Crowley and co-workers (1984) used a 4-cm pocket dimension to predict fetal distress in postterm
pregnancies. Phelan and co-workers (1987) introduced the now-popular technique termed the amnionic
fluid index. This technique is described in detail in Chapter 29 , and normal values are shown in Table
29–3 and Figure 29–2.

9. ASSESSMENT OF FETAL WELL-BEING

The biophysical profile is a test used in conjunction with antepartum fetal heart rate testing to
evaluate fetal well-being in high-risk pregnancies.57 The test quantifies fetal breathing and body
movements, fetal tone, and amniotic fluid volume. It also incorporates the nonstress test as a measure
of fetal reactivity. Each of these five parameters are assigned a score of 2 if normal and 0 if abnormal
(Table 3). The fetus is observed until all parameters are seen or until 30 minutes has elapsed.
This observation period helps to distinguish the normal fetus with a physiologic periodic sleep
cycle from the chronically asphyxiated fetus with central nervous system depression. Fetal breathing
movements occur about 30% of the time and, when seen, demonstrate that a complex fetal central
nervous system function is intact.58 Fetal breathing movements are seen in the normal fetus after 24
weeks' gestation.59
A normal biophysical profile (score of 8 to 10) is associated with a corrected perinatal mortality
rate of 1 to 2 per 1000.60 A test score of 6 indicates the need to repeat testing within 24 hours. Scores
of 4 or less are highly predictive of intrauterine fetal jeopardy and, in a term fetus, are an indication for
delivery. Low scores are associated with fetal distress in labor as well as low Apgar scores. Vintzileos
and colleagues61 observed a good correlation between a low biophysical profile and fetal acidosis.
In the extremely preterm fetus, a low score may not necessarily indicate the need for immediate
delivery. The clinician must weigh the risk of fetal distress or demise with the risks of prematurity. In
this clinical situation, stabilizing any adverse maternal condition (such as elevated blood glucose in a

52
diabetic patient or high blood pressure in a hypertensive patient) and repeating the biophysical test a
short time later may be indicated.

10. ASSESSMENT OF THE RISK OF PRETERM LABOR

There has been considerable interest in ultrasonographic evaluation of the cervix as a marker for
assessing the risk of preterm birth (Fig. 17). Iams and colleagues62 published a large multicenter study
confirming that patients with a short cervix, as determined by endovaginal ultrasonography, are at
increased risk of preterm birth. It is clear that the length of the cervix decreases with advancing
gestational age and that there is no cervical length at which the risk of preterm birth is zero. A cervical
length of less than 30 mm, however, does appear to indicate an increased risk of preterm birth. Cervical
length may provide a more objective and clinically effective means of assessing the cervix in patients
with cervical cerclage.

11. GUIDING INVASIVE PROCEDURES

Ultrasound can be used to localize a favorable pocket of amniotic fluid before performing
amniocentesis.63 The needle can be inserted under direct visualization using the real-time scanner.64 A
needle guide is available to aid the obstetrician with needle placement, but this can limit the operator's
ability to move the needle in three dimensions. It is preferable to insert the needle in a co-planar
fashion (i.e., in the same longitudinal plane as the ultrasound transducer), so that the entire length of the
needle track can be seen. Transplanar placement (i.e., perpendicular to the ultrasound plane) limits
ultrasound view of the needle.
In chorionic villus sampling, the catheter is inserted into the placental bed under ultrasound
guidance.65 Similarly, simultaneous real-time ultrasound guidance is used in percutaneous umbilical
blood sampling or cordocentesis.66

53
DOPLLER

FETAL CIRCULATION
ANATOMY OF FETAL CIRCULATION
In an adult, blood circulates from the left ventricle to the systemic circulation and is returned
to the right side of the heart. From there it circulates through the lungs for reoxygenation. This serial
circulatory design is inappropriate for a fetus because oxygenation occurs in the placenta, and a pair of
parallel circulations is present. This is made possible by anatomical shunts, which normally close
rapidly at birth when circulation independent of the mother is required.1
The fetal circulation is illustrated in Figure 1, which shows approximate values of the percent
saturation of blood with oxygen in various areas. Most of the physiological data presented here are
from chronically catheterized, unanesthetized sheep fetuses, because it is not possible to obtain such
data from humans. Although species differences may occur, it is likely that some general trends and
mechanisms also apply to humans.
Well-oxygenated blood returns to the fetus from the placenta by way of the umbilical vein.
The umbilical vein enters the liver, where it joins with the portal venous system. Some of this blood is
shunted directly to the inferior vena cava through the ductus venosus, while some traverses the hepatic
parenchyma. An average of 50% takes the latter path, but the proportion is quite variable.
The saturation of blood in the inferior vena cava is lower than that in the ductus venosus,
because it has mixed with poorly oxygenated blood returning from the lower body. However, this
mixture is not complete, and a streaming of blood within the proximal inferior vena cava has been
described. The inferior vena cava blood enters the right atrium, and approximately 40% is diverted to
the left atrium through the foramen ovale. Most of the blood crossing the foramen ovale corresponds to
the stream of well-oxygenated blood in the inferior vena cava coming from the ductus venosus. In the
left atrium, this blood mixes with a relatively small quantity of pulmonary venous blood, enters the left
ventricle, and then proceeds to the coronary circulation and vessels supplying the head, neck, and upper
extremities. Blood entering the right atrium from the superior vena cava joins with the remaining (60%)
blood in the inferior vena cava, which corresponds mainly to the less-oxygenated bloodstream from the
distal inferior vena cava (fetal lower body). This blood enters the right ventricle. From here a small
proportion enters the pulmonary circulation, but most is shunted from this bed through the ductus
arteriosus, which joins the descending aorta. This blood supplies the gut, kidneys, lower body, and also
the umbilical circulation.2
Following the route just described, the blood perfusing the fetal lower body is ejected from
both the right and left ventricles, while blood perfusing the upper body is ejected from the left
ventricle. The differential streaming and the fact that inferior vena cava blood crosses the foramen
ovale accounts for the about 5% to 10% higher oxygen saturation observed in the ascending aorta
(blood perfusing "vital" organs such as the brain and heart) than in the descending aorta.

DISTRIBUTION OF BLOOD FLOW

The distribution of blood flow in a fetus is generally described as a percentage of the cardiac
output. This is a simple concept in an adult, who has two essentially equal serial circulations: systemic
and pulmonary. In a fetus, which has two unequal parallel circulations, distribution is described as the
percentage of combined ventricular output (CVO), the combined output of left and right ventricles.
The percentage of CVO in various areas of the heart and other vessels is shown in Figure 2.3
For obvious reasons, little of this information is available in term infants, and the values are obtained
from unanesthetized chronically catheterized term sheep fetuses.
The human fetal cardiac output at term has been estimated to be about 500 ml/minute/kg,
according to data obtained from noninvasive measurements.4 A term sheep fetus is similar in weight to

54
a human fetus (approximately 7 pounds [3.2 kg]), but species differences may occur (e.g., in the
proportion of blood flow to the brain). Values of central blood flow in milliliters per minute per
kilogram fetal body weight are shown in Figure 3. Note that the CVO is 450 ml/minute/kg, with twice
as much from the right as the left ventricle. About 40% of the CVO is umbilical blood flow (i.e., about
200 ml/minute/kg). The remaining 60% of CVO distribution to the fetal organs has been determined in
fetal sheep. With minor variations among studies, typical values of organ blood flow expressed as
percent of the CVO and as ml/minute x 100 g are shown in Table 1.5

FETAL BLOOD PRESSURES

The fetus is surrounded by the fluid-filled amniotic cavity, so pressures must be related to that
of amniotic fluid. In the absence of uterine contractions, this latter pressure is generally stable.
Fetal systemic arterial blood pressure is considerably lower than that in an adult, averaging 55
mm Hg (systolic/diastolic, approximately 70/45 mm Hg) at term. Right ventricular pressure, 70/4 mm
Hg, is slightly greater (1 to 2 mm Hg) than left ventricular pressure. Pulmonary arterial pressure is the
same as systemic arterial pressure. There is a slightly greater pressure in the right atrium (3 mm Hg)
than in the left atrium (2 mm Hg), thus ensuring right-to-left blood flow across the foramen ovale.
Pressure in the systemic venous bed is similar to that of the right atrium, with the exception of the
umbilical vein, where pressure is about 8 to 10 mm Hg.
Systemic blood pressures are somewhat lower earlier in gestation. This is reflected in the fact
that premature newborns have lower blood pressure than term infants. Thus, at 30 weeks gestation the
mean arterial blood pressure is only 35 mm Hg.

FETAL HEART RATE

Fetal heart rate analysis is the prime means by which a fetus is evaluated for adequacy of
oxygenation, so knowledge of its rate and regulation are of great importance to an obstetrician.
The average heart rate in a nonmedicated term fetus before labor is 140 beats/minute (bpm).
Earlier in pregnancy it is higher than this, although not substantially so. At 20 weeks gestation, the
average fetal heart rate is 155 bpm, and at 30 weeks gestation, it is 144 bpm. Variations of 20 bpm
above or below these values are encountered in normal fetuses.
A fetal heart is similar to that of an adult in that it has its own intrinsic pacemaker activity that
results in rhythmic contractions. The sinoatrial (SA) node, which is found in one wall of the right
atrium, has the fastest rate of contraction, and it sets the rate in a normal heart (Fig. 4). The next fastest
pacemaker rate is found in the atrium, and finally, the ventricle has a slower rate of beating than either
the SA node or atrium. In various cases of complete or partial heart block in a fetus, variations in rate
below normal can be encountered. A fetus with complete heart block typically has a rate of about 60
bpm.
The mean fetal heart rate is a result of many physiological factors that modulate the intrinsic
rate of the heart.

CARDIAC OUTPUT REGULATION

In adults, the beat-to-beat amount of blood pumped by the heart is determined by the amount
of blood returning to the heart. In accordance with the Frank-Starling mechanism, when the cardiac
muscle is stretched before contraction by an increased inflow of blood, it contracts with a greater force
than before and is able to pump out more blood. In other words, the heart pumps all the blood that
flows into it without excessive damming of blood in the veins. This mechanism has been studied in
unanesthetized fetal lambs and has been shown to be less developed than in adult sheep. The imperfect
mechanism in the fetal lamb is probably due to the fact that the heart muscle is not as well developed as
in the adult sheep. It is likely that the same is true of a human fetus, as it is generally more immature
than a fetal lamb when born. As a consequence, increases in the filling pressure or preload produce

55
minor if any changes in CVO, suggesting that the fetal heart normally operates near the top of its
function curve.
The output of the fetal heart is also related to the heart rate. Some researchers have shown that
spontaneous variations of heart rate relate directly to cardiac outputthat is, as rate increases, output
increases. However, different responses have been observed during right or left atrial pacing studies.
No changes were observed in left ventricular output when the right atrium was paced, whereas the
output decreased during left atrial pacing.6 Clearly, additional factors are operating to explain such
differences. The relationship between fetal heart rate and cardiac output has not been confirmed in
human fetuses under physiologic conditions, because the spontaneous increase in heart rate has been
found to be associated with a decrease in stroke volume, maintaining the cardiac output unchanged.7
In addition to heart rate and preload, cardiac output depends on afterload and intrinsic
contractility. The fetal heart appears to be very sensitive to changes in the afterload, represented by the
fetal blood pressure. In this way, increases in after-load dramatically reduce the stroke volume or
cardiac output. As has already been stated, the fetal heart is incompletely developed compared to that of
adults. Many ultrastructural differences between the fetal and adult heart account for a lower intrinsic
capacity of the fetal heart to contract. Each of these four determinants of cardiac output do not work
separately, but rather they interact dynamically to modulate the fetal cardiac output during physiologic
conditions. Cardiac output responses during hypoxic bradycardia are described later.

REGULATION OF FETAL CIRCULATION

PARASYMPATHETIC NERVOUS SYSTEM

The parasympathetic nervous system consists primarily of the vagus nerve (tenth cranial
nerve), which originates in the medulla oblongata. Fibers from this nerve supply the SA node and also
the atrioventricular node (AV) (see Fig. 4). Stimulation of the vagus nerve or injection of its mediator,
acetylcholine, results in a decrease in heart rate in a normal fetus due to vagal influence on the SA
node, decreasing its rate of firing and decreasing the rate of transmission of impulses from atrium to
ventricle. In a similar fashion, blocking of this nerve in a normal fetus with a substance that blocks the
effects of acetylcholine (e.g., atropine) causes an increase in the fetal heart rate of approximately 20
bpm at term. This demonstrates that there is normally a constant vagal tone on the fetal heart rate,
tending to decrease it from its normal intrinsic rate.
The vagus nerve is also responsible for transmission of impulses causing beat-to-beat
variability of fetal heart rate. Blocking the vagus nerve with atropine results in a disappearance of this
variability. Hence, it has been postulated that two vagal influences impinge on the heart: a tonic
influence tending to decrease its rate and an oscillatory influence that results in fetal heart rate
variability.

Sympathetic Nervous System

Sympathetic nerves are widely distributed in the myocardium at term (see Fig. 4). Stimulation
of the sympathetic nerves will release norepinephrine and cause an increase in fetal heart rate and also
an increase in the vigor of cardiac contractions. These result in an increase in cardiac output. The
sympathetic nerves are a reserve mechanism to improve the pumping activity of the heart during
intermittent stressful situations. There is normally a tonic sympathetic influence on the heart.
When the b-adrenergic receptor blocker propranolol is administered to a normal fetus, the fetal
heart rate will decrease approximately 10 bpm. There is, however, only a small decrease in fetal heart
rate variability after blocking the sympathetic nerves.
a-Adrenergic receptors also are found in a fetus at term. When they are stimulated with
methoxamine, there is an increase in blood pressure and a decrease in the kidney and carcass blood
flow. The opposite is observed after a-adrenergic blockers as phentolamine or phenoxybenzamine.8
Several factors cause the parasympathetic and sympathetic nervous systems to increase their
activity.

56
BARORECEPTORS

In the walls of the arch of the aorta and in the carotid sinus at the junction of the internal and
external carotid arteries are found small stretch receptors that are sensitive to increases in blood
pressure (Fig. 5). When blood pressure rises, impulses are sent from these receptors by way of the
vagus and glossopharyngeal nerve to the midbrain, resulting in further impulses through the vagus
nerve to the heart, tending to slow it. This is an extremely rapid response, being noted with almost the
first increase of blood pressure. It is a protective, stabilizing function by the body attempting to lower
blood pressure by decreasing heart rate and cardiac output when blood pressure is increasing.

CHEMORECEPTORS

Chemoreceptors are found in both the peripheral and central nervous systems. They have their
most dramatic effects on the regulation of respiration, but they are still important in the control of the
circulation. The peripheral chemoreceptors are found in the carotid and aortic bodies (see Fig. 5). Like
the pressoreceptors, they are found in the arch of the aorta and in the area of the carotid sinus. The
central chemoreceptors, found in the medulla oblongata, respond to changes in the oxygen and carbon
dioxide tensions in blood or cerebrospinal fluid perfusing this area.
In adults, when oxygen in the arterial blood perfusing the central chemoreceptors is decreased
or the carbon dioxide content is increased, there is ordinarily a reflex tachycardia. There is also a
substantial arterial blood pressure increase, which is extremely pronounced with increases in carbon
dioxide concentration. Both of these effectsthat is, tachycardia and an increase in blood pressureare
thought to be protective in attempting to circulate more blood through the affected areas in order to
bring about a decrease in carbon dioxide tension or an increase in oxygen. Effects in the fetus are not
known.
The peripheral chemoreceptors seem to be highly important in the cardiovascular responses to
hypoxia. The interaction of baroreceptor and chemoreceptor systems in a fetus is not well understood,
although the net result of hypoxia in a fetus is bradycardia and hypertension. During basal conditions,
they seem to contribute to stabilize heart rate and blood pressure.9

CENTRAL NERVOUS SYSTEM

It has been established that in adults there are influences on heart rate from the higher centers
of the brain (Fig. 6). Heart rate can be increased by various emotional stimuli such as fear or sexual
arousal. Observations of fetal lambs and monkeys have shown that the electroencephalogram or
electro-oculogram shows increased activity at times in association with variability of the heart rate and
body movements. At other times, apparently when the fetus is sleeping, activity slows and the fetal
heart rate variability decreases, suggesting an association between these two factors and central nervous
system activity.
The hypothalamus is thought to be the area of dispatch of nerve impulses produced by
physical expressions of emotion, including acceleration of the heart rate and elevation of the blood
pressure. It has been shown in fetal lambs that stimulating an electrode in the hypothalamus causes the
fetal heart rate to increase, at least initially, followed by a decrease, probably because of the baroflex
mentioned earlier. The increase in blood pressure and heart rate appears to be mediated by the
sympathetic nerves.
The medulla oblongata contains the vasomotor center, an integrative center where the net
input results in either cardioacceleration or cardiodeceleration.

HUMORAL REGULATION

ADRENAL MEDULLA. The fetal adrenal medulla produces epinephrine and norepinephrine in
response to stressful situations (e.g., hypoxia). Both of these substances act on the heart and

57
cardiovascular system in a way similar to sympathetic stimulation. That is, they produce a faster heart
rate, greater force of contraction of the heart, and an increased arterial blood pressure. However, it is
not clear whether catecholamines exert a regulatory function in a resting fetus, at least in sheep.10

RENIN-ANGIOTENSIN SYSTEM. Angiotensin II seems to play a role in fetal circulatory

regulation at rest, but its main activity is observed during hemorrhagic stress on a fetus.

VASOPRESSIN. Vasopressin has been shown to affect the distribution of blood flow in fetal
sheep. However, this is probably only operative during hypoxia and possibly other stressful situations.

PROSTAGLANDINS. Arachidonic acid metabolites are found in high concentrations in the

fetal circulation and in many tissues. Their main role seems to be in the regulation of umbilical blood
flow as well as in maintaining the patency of the ductus arteriosus during fetal life.
Other hormones such as a-melanocyte-stimulating hormone (a-MSH), atrial natriuretic
hormone, neuropeptide Y, thyrotropin-releasing hormone (TRH), and metabolites such as adenosine
have also been described to be present in the fetus and to participate in the circulatory function
regulation, but their importance is still not determined.

BLOOD VOLUME CONTROL

CAPILLARY FLUID SHIFT. In adults, when the blood pressure of the body is elevated by
excessive blood volume, some fluid moves out of the capillaries into interstitial spaces, thereby
decreasing the blood volume back toward normal. Conversely, if an adult loses blood through
hemorrhage, some fluid shifts out of the interstitial spaces into the circulation, thereby increasing the
blood volume back toward normal. There is normally a delicate balance between the pressure inside
and outside the capillaries. This mechanism to regulate blood pressure is slower than the almost
instantaneous regulation found with the reflex mechanisms discussed earlier. Its role in a fetus is
imperfectly understood, but studies performed on sheep show that a fetus appears to be able to keep its
blood volume closer to normal than an adult after reductions or expansions of volume.11

INTRAPLACENTAL PRESSURES. Fluid moves down hydrostatic pressure gradients and also
in response to osmotic pressure gradients. The actual values of these factors within the placental site
where fetal and maternal blood closely approximate are controversial. It seems likely, however, that
some delicate balancing mechanisms within the placental site prevent rapid fluid shifts between mother
and fetus. As noted earlier, maternal arterial blood pressure is much higher (approximately 100 mm Hg)
than that of a fetus (approximately 55 mm Hg); hence, some compensatory mechanism must be present
to equalize the effective pressures at the exchange points. Imbalances may be responsible for the
hydrops encountered in some cases of Rh isoimmunization and extreme fetal tachycardia.

OXYGEN TRANSFER TO THE FETUS

It is likely that most stillbirths and cases of fetal depression are the result of inadequate
exchange of the respiratory gases. Oxygen has the lowest storage-to-utilization ratio of all nutrients in a
fetus. From animal experimentation it can be calculated that in a term fetus the quantity of oxygen is
approximately 50 ml and the normal oxygen consumption is approximately 21 ml/minute. This means
that in theory, a fetus has a 2- to 3-minute supply of oxygen. Fetuses do not, however, consume the
total quantity of oxygen in their bodies within 3 minutes, nor do they expire after this time. In fact,
irreversible brain damage does not occur until about 10 minutes have elapsed. This is because a fetus
has a number of important compensatory mechanisms that enable it to survive on a lesser quantity of
oxygen for longer periods. This is discussed in a later section. The clinical situations in which there is
total cessation of oxygen delivery are rare. These include sudden total abruption of the placenta or
complete umbilical cord compression, generally after prolapse of the cord.

58
 It is of value to examine the factors that determine oxygen transfer from mother to fetus (Table
2).12 Because the transfer of oxygen to a fetus is dependent on rates of blood flow and not limitations
of diffusion, the blood flow on each side of the placenta assumes major importance for maintenance of
fetal oxygenation. Studies of animals suggest that in the normal placenta there is a safety factor of
approximately 50% in the uterine blood flow. That is, the uterine blood flow can drop to half its normal
value before fetal acidosis becomes evident. This applies only to the normal situation with normal
placental reserve and is unlikely to be so in pathologic situations, such as an infant of a hypertensive
mother. In this situation, placental function may be adequate for oxygenation but not for fetal growth,
and a growth-retarded infant may result from such a pregnancy. Furthermore, with superimposition of
uterine contractions on such a fetus, there may be transient inadequacy of uterine blood flow (and
hence fetal oxygenation) during the uterine contractions; this may be recognized by responses of the
fetal heart ratenamely, late decelerations.
Additional important determinants of fetal oxygenation include oxygen tension in maternal
arterial and fetal arterial blood. In general, maternal arterial oxygen tension depends on adequate
ventilation and pulmonary integrity. Disruptions of this function are relatively rare in obstetrics,
although they can occur with pulmonary disease such as asthma, with congestive heart failure, or in
mothers with congenital cardiac defects. The oxygen affinity and oxygen capacity of maternal and fetal
blood are also important determinants of fetal oxygen transfer.
At a given oxygen tension, the quantity of oxygen carried by blood depends on the oxygen
capacity (which is dependent on the hemoglobin concentration) and the oxygen affinity. The oxygen
affinity of fetal blood is greater than that of maternal blood. That is, the oxygen dissociation curve of a
fetus is to the left of that of the mother. In addition, the hemoglobin concentration of fetal blood is
approximately 15 g/100 ml in a term fetus, whereas that of the mother is approximately 12 g/100 ml.
Both of these factorsan increased oxygen affinity and higher oxygen capacityconfer advantages to a
fetus for oxygen uptake across the placenta. Probable values of the oxygen content and oxygen tension
in umbilical vessels and maternal uterine artery and vein are illustrated in Figure 7.
Because most measurements have been made in a human fetus during or after labor and
delivery, the values of oxygen saturation and pH are generally depressed compared with those of an
adult. In fact, investigations on chronically instrumented animals and data obtained from human fetuses
by cordocentesis13 have shown that the oxygen saturation and content of fetal blood and acid-base
status are very close to that of maternal blood. Only the oxygen tension is lower. The arteriovenous
oxygen differences across each side of the placenta are also illustrated in Figure 7. Notice that the
quantity of oxygen delivered or taken up by each 100 ml of circulating blood in the placenta is
approximately equal in the mother and fetus. This suggests approximate equality of blood flow on each
side of the placenta. A number of additional miscellaneous factors determine the rate of oxygen transfer
across the placenta; they are listed in Table 2 as the last six determinants. They appear to be relatively
minor compared with the major factors already outlined.

CARBON DIOXIDE AND ACID-BASE BALANCE

Carbon dioxide crosses the placenta even more readily than does oxygen. In general, the
determinants for oxygen transfer also apply to carbon dioxide. It is limited by rate of blood flow and
not by resistance to diffusion. The carbon dioxide tension in fetal blood in the undisturbed state is close
to 40 mm Hg. It is well known that maternal arterial carbon dioxide tension is approximately 34 mm
Hg and that a pregnant woman is in a state of compensated respiratory alkalosis. The pH of fetal blood
under undisturbed conditions is probably close to 7.4, and the bicarbonate concentration is close to that
in maternal blood.
Bicarbonate and the fixed acids cross the placenta much more slowly than does carbon
dioxide, (i.e., equilibration takes a matter of hours rather than seconds). A situation analogous to
respiratory acidosis occurs in the fetus when blood flow, either uterine or umbilical, is acutely
compromised. In such cases, the pH drops and carbon dioxide tension is elevated, but the metabolic
acid-base status remains unchanged. This occurs during severe variable decelerations in association
with uterine contractions, especially during the second stage of labor. These acid-base changes are
generally rapidly resolved with cessation of the contraction and the deceleration. However, if

59
significant oxygen lack is unrelieved, the fetus will decrease its oxygen consumption, redistribute blood
flow, and depend partly on anaerobic metabolism to supply its energy needs, albeit with decreased
efficiency. Under these conditions, lactate (an end product of anaerobic metabolism) is produced,
resulting in metabolic acidosis. The acidosis may also be aggravated by a combined respiratory acidosis
because of retained carbon dioxide. Unlike carbon dioxide, lactate is lost rather slowly from a fetus.

UTERINE BLOOD FLOW

Because uterine blood flow is one of the prime determinants of passage of the respiratory
gases across the placenta, its characteristics and the factors affecting it will be discussed.14 This subject
is reviewed in more detail elsewhere in this book.
Uterine blood flow in a term fetus is approximately 700 ml/minute. This represents about 10%
of the cardiac output. Approximately 70% to 90% of the uterine blood flow passes through the
intervillous space, and the remainder largely supplies the myometrium.
The uterine vascular bed is thought to be almost maximally dilated under normal conditions,
with little capacity to dilate further. It is not autoregulated, so flow is proportional to the mean
perfusion pressure. However, it is capable of marked vasoconstriction by a-adrenergic action. It is not
responsive to changes in respiratory gas tensions. The uterine blood flow is determined by the
following relationship:

Uterine blood flow =

uterine arterial pressure - uterine venous pressure

uterine vascular resistance

Hence, any factor affecting either of the three values on the right-hand side of the above
relationship will alter uterine blood flow. A number of causes of decreased uterine blood flow are
shown in Table 3.
Uterine contractions decrease uterine blood flow as a result of increased uterine venous
pressure brought about by increased intramural pressure of the uterus. There may also be a decrease in
uterine arterial pressure with contractions. Uterine hypertonus causes decreased uterine blood flow
through the same mechanism.
In sheep, it has been shown that if uterine arterial perfusion pressure is altered without
changing the resistance of the uterine vascular bed, there is a direct relationship between uterine blood
flow and the pressure. Hence, hypotension due to any of the mechanisms noted in Table 3 will cause a
decrease in blood flow.
In the case of maternal arterial hypertension, it is likely that there is a concomitant increased
vascular resistance that is shared by the uterine vascular bed. This, therefore, results in a decrease in
uterine blood flow. Either endogenous or exogenous vasoconstrictors result in decreased blood flow
because of increased uterine vascular resistance.
There are few useful means of increasing uterine blood flow in cases in which it is known to
be less than optimal. The most important clinical considerations are the avoidance or correction of
factors responsible for an acute decrease in blood flow, such as excessive uterine activity or maternal
hypotension.
Clinically it has been known for many years that maternal bed rest may improve the outcome
in suspected fetal growth retardation. There is now some evidence that bed rest does improve fetal
growth, as evidenced by increasing estriol excretion.
Some of the b-mimetic agents that are used as uterine relaxants for premature labor may
increase uterine blood flow, but this effect is still under investigation. There are a number of
experimental means of increasing uterine blood flow, sometimes transiently, but these have no place
clinically. Examples of such treatments include estrogens, acetylcholine, nitroglycerin, cyanide,
ischemia, and chronic hypoxia.

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UMBILICAL BLOOD FLOW
Umbilical blood flow measured by ultrasonographic techniques is about 360 ml/minute, or
120 ml/minute/kg in an undisturbed fetus15 at term. This figure is considerably less than that of a
sheep, where it is approximately 200 ml/minute/ kg. The differences may be explained by the
somewhat higher metabolic rate (body temperature 39°C) and lower hemoglobin concentration (10
g/dl) in a fetal sheep. It is important to recognize this species difference, because most of our
information on fetal circulatory physiology comes from fetal sheep. The umbilical blood flow is
approximately 40% of the combined ventricular output, and about 20% of this blood flow is
shuntedthat is, it does not exchange with maternal blood in sheep. It is either carried through actual
vascular shunts within the fetal side of the placenta or else it does not approach maternal blood closely
enough to exchange with it.
Umbilical blood flow is unaffected by acute moderate hypoxia but is decreased by severe
hypoxia. Innervation of the umbilical cord is still questionable, but umbilical blood flow decreases with
the administration of catecholamines. It is also decreased by acute cord occlusion. There are no known
means of increasing umbilical flow in cases in which it is thought to be decreased chronically.
However, certain fetal heart rate patternsnamely, variable decelerationshave been ascribed to transient
umbilical cord compression in a fetus during labor. Manipulation of maternal position either to the
lateral or Trendelenburg's position can sometimes abolish these patterns; the implication is that cord
compression has been relieved.

HYPOXIA

FETAL RESPONSES

Studies of chronically prepared animals have shown that a number of responses occur during
acute hypoxia or asphyxia in a previously normoxic fetus. There is little or no change in combined
cardiac output and umbilical (placental) blood flow, but there is a redistribution of blood flow favoring
certain vital organsnamely, heart, brain, and adrenal glandsand a decrease in the blood flow to the gut,
spleen, kidneys, and carcass.16 This initial response is presumed to be advantageous to a fetus in the
same way as the diving reflex is in an adult seal, in that the blood containing the available oxygen and
other nutrients is supplied preferentially to vital organs.
Fetal oxygen consumption decreases to values as low as 60% of control (from approximately
8 to 5 ml/minute/kg) during fetal hypoxia in a chronically instrumented fetus with arterial oxygen
tension of 10 mm Hg. This decrease is rapidly instituted, stable for periods up to 45 minutes,
proportional to the degree of hypoxia, and rapidly reversible on cessation of maternal hypoxia. It is
accompanied by a fetal bradycardia of about 30 bpm below control (approximately 170 bpm control to
140 bpm hypoxia in fetal sheep) and an increase in fetal arterial blood pressure (approximately 54 mm
Hg control to 61 mm Hg hypoxia mean pressure). There is also progressive fetal acidosis during fetal
hypoxia (fetal arterial pH 7.38 control to 7.33 after 25 minutes hypoxia). This is an exclusively
metabolic acidosis and is likely to be a lactic acidosis as a result of anaerobic metabolism, presumably
in those partially vasoconstricted beds where oxygenation is inadequate for normal basic needs. During
fetal asphyxia, the increase in carbon dioxide tension superimposes a respiratory component on the
acidosis.
The series of responses just describedthat is, redistribution of blood flow favoring vital organs,
decreased total oxygen consumption, and anaerobic glycolysismay be thought of as temporary
compensatory mechanisms that enable a fetus to survive moderately long periods (e.g., up to 30
minutes) of limited oxygen supply without decompensation of vital organs, particularly the brain and
heart. The close matching of blood flow to oxygen availability to achieve a constancy of oxygen
consumption has been demonstrated in the fetal cerebral circulation. In studies on hypoxic lamb
fetuses, cerebral oxygen consumption was constant over a wide range of arterial oxygen contents

61
because the decrease in arteriovenous oxygen content accompanying hypoxia was compensated for by
an increase in cerebral blood flow.
However, during more severe asphyxia or sustained hypoxemia, these responses are no longer
maintained, and a decrease in the cardiac output, arterial blood pressure, and blood flow to the brain
and heart have been described (Fig. 8). These changes may be considered to be a stage of
decompensation, after which tissue damage and even fetal death may follow.17

METABOLIC EFFECTS

It is known that a fetus depends partially on anaerobic metabolism for its energy needs during
oxygen insufficiency.18 It has also been shown in experimental animals that a newborn's ability to
tolerate asphyxia depends on cardiac carbohydrate reserves. Whether this also applies to a human fetus
is unknown, but clinical observations support the view that carbohydrate-depleted fetuses succumb
more readily than those with normal reserves. A nutritionally growth-retarded fetus also is more
susceptible to intrauterine asphyxia and depression than a normal fetus.19
It has been stated that the prime aim of compensatory responses in hypoxia is maintenance of
the circulation, and maintenance of the integrity of cardiac function is paramount in this regard. It is
likely that carbohydrate availability is critical in supplying substrates for glycolysis at more severe
degrees of hypoxia.

MECHANISMS OF RESPONSES

The cardiovascular responses to hypoxia are instituted rapidly and are mediated by neural and
hormonal mechanisms (Fig. 9). As it has been previously mentioned, the tonic influence of the
autonomic nervous system on heart rate, blood pressure, and the umbilical circulation in a normoxic
fetus is quantitatively minor. This is in marked contrast to autonomic activity during hypoxia.
In studies using total pharmacologic blockade, it has been shown that parasympathetic activity
is augmented three to five times and b-adrenergic activity doubles when measured by heart rate
response. The net result of these changes is a decrease in fetal heart rate during hypoxia. Augmented b-
adrenergic activity also may be important in maintaining cardiac output and umbilical blood flow
during hypoxia, probably by increased inotropic effect on the heart.
a-Adrenergic activity is important in determining regional distribution of blood flow in
hypoxic fetal sheep by selective vasoconstriction. As noted earlier, during hypoxia there is preferential
blood flow to the brain, heart, and adrenals and decreased supply to the carcass, lungs, kidneys, and
gut. a-Adrenergic blockade reversed the hypertension and increased peripheral resistance observed
during fetal hypoxia. These changes are due to a decrease in the resistance in the gut, spleen, lungs, and
probably carcass, indicating a participation of the a-adrenergic system in their vasoconstriction.
Plasma concentrations of catecholamines, vasopressin, b-endorphin, and atrial natriuretic
factor increase during hypoxia in a fetus. The contributions of catecholamines to the circulatory
responses to hypoxia were described earlier. Vasopressin contributes to the increase in blood pressure
observed during hypoxia by decreasing umbilical and gut blood flows. b-Endorphin and probably other
endogenous opioids also participate in the response to hypoxia. The blockade of its receptors with
naloxone further increases the hypertensive response by increasing the vasoconstriction in the kidneys
and carcass. During hypoxia, a decrease in the fetal blood volume has been described. Atrial natriuretic
factor may play a role in this response. Most of these results have been obtained from the chronically
catheterized fetal sheep model. The relative contribution of these and other mediators to the
cardiovascular response to hypoxia in a human fetus and their potential use as therapeutic tools are
being explored.

UTERINE AND PLACENTAL BLOOD FLOW

It should be obvious to any student of maternal-fetal medicine that a multiplicity of factors
contribute to that intrauterine environment which permits normal growth and development of the fetus

62
and also provides a safety factor for survival under stressful conditions. Aberrations of this
environment are often referred to by such terms as uteroplacental insufficiency and placental
dysfunction, which are no more than vague approximations of a less than optimal fetal environment. If,
however, one considers those elements that must have a significant impact on the fetal environment,
placental blood flow (PBF) is a critical factor. This is so not only because maternal blood carries
necessary foodstuffs to the fetus and removes waste products throughout pregnancy but also because
the quantity of oxygen delivered to the placenta is limited directly by the rate of PBF. Thus, since
oxygen deprivation is such a critical determinant of fetal well-being, knowledge of that most important
factor controlling oxygen delivery, PBF, is crucial irrespective of other compensatory responses.
In the half century since Barcroft and associates first quantitated uterine blood flow (UBF) in
the pregnant rabbit, a significant body of knowledge has developed.1 Although we know the most
about UBF and PBF in lower animals, primarily the ovine species, correlative data in subhuman
primates and a paucity of observations in women indicate that despite obvious species variations in
placentation, general principles of uterine vascular control are quite comparable.

DEVELOPMENT OF THE PLACENTAL CIRCULATION AND

HOMEOSTASIS
The uterine circulation is exquisitely sensitive to estrogen stimulation, responding with a
degree of vasodilatation unparalleled by any other organ of the body to any other stimulus.2 During the
ovarian cycle, repetitive patterns of UBF occur reflecting the effect of estrogen secretion and the
modulating effects of progesterone. These cyclic patterns are demonstrated most dramatically in
animals with short preovulatory cycle phases, such as the cow, sow, and ewe, and are illustrated in
Figure 1 with peripheral levels of estrogen and progesterone.3, 4, 5 Following conception in these
species, UBF patterns are similar to those in nonpregnant animals until interdigitation of maternal and
fetal tissues occurs 17 to 28 days later; then, there is a definitive and progressive increase in UBF that
continues until term pregnancy. Since erosion of endometrium by fetal trophoblast occurs much earlier
after conception in the primate, it is reasonable to presume that UBF increases earlier in these species,
although such responses have never been observed. The overall patterns of total UBF, UBF per unit
weight of uterus and its contents, fraction of UBF supplying the placenta, and fetal weight throughout
ovine pregnancy are illustrated in Figure 2. The period between 17 and 70 days of gestation is
associated with the most rapid changes in UBF and PBF and corresponds with the time of definitive
placentation in this species. By mechanisms incompletely understood, blood vessels supplying the
placenta progressively dilate during this time, simultaneously causing an absolute increase in total UBF
and shunting of this blood from nonplacental to placental tissues.* With subsequent placental
maturation, the fraction of UBF supplying the placenta and the absolute amount of PBF increase, but at
rates more similar to that of fetal growth; thus, during the last half of pregnancy, UBF per unit weight
of uterus and its contents is essentially constant. During this same time, the amount of oxygen extracted
from each milliliter of blood is constant and therefore the amount of oxygen delivered per given weight
of gravid uterus is also constant.6 Correlative studies in women indicate similar homeostatic patterns
from 10 to 40 weeks of gestation and similar oxygen consumption (approximately 10 ml/kg).7 Since
women deliver the same amount of oxygen at lower UBF rates than the ewe (~150 versus ~270 ml/kg),
it follows that the human placenta is more efficient in this regard. Thus, for fetuses of similar weight,
less absolute UBF is required and the pregnancy load on the heart is diminished.
Changes in PBF are accomplished by an ever-increasing vasodilatation of the blood vessels
supplying the placenta throughout the course of gestation. However, at any given moment during the
second and third trimesters, essentially no further acute vasodilatation of these vessels can occur.
Therefore, to maintain constant oxygen delivery during episodes of reduced PBF, increased oxygen
extraction must occur (Fig. 3). Based on reported data, it would appear that the limit of increased
extraction is twofold. Thus, PBF has to be reduced more than 50% before oxygen delivery is
diminished. These considerations assume that the rate of homeostatic PBF was optimal prior to the
flow reduction. We know, however, that homeostatic levels may be suboptimal either sub-acutely, as in
toxemia, or chronically, as in nephropathies. In such cases, the safety factor, that is, the percent that

63
PBF can be reduced before oxygen delivery is compromised, is lowered. This must always be
considered when one evaluates the effect of an acute stimulus on the fetus.

*In man and subhuman primates, the spiral arterioles that will supply the intervillous space
(approximately one per placental cotyledon) lose their capillary connections and dilate about tenfold as
the result of replacement of the vessel walls by trophoblast. This process may extend to or below the
myoendometrial junction, literally turning the spiral arterioles into spiral arteries. Blood flowing
through these modified blood vessels into the intervillous space comprises PBF.
In the ovine species, multiple discrete areas of endometrium called caruncles are present in the
nonpregnant state. During pregnancy, interdigitation of fetal and maternal tissues occurs in these
caruncles, which enlarge to become individual placental cotyledons. Blood flowing to these areas
collectively comprises PBF. Although the cotyledonary arterial blood vessels dilate significantly, they
contain no trophoblastic elements, maternal-fetal transfer is by a capillary-capillary interface, and no
intervillous space is present.

DYNAMIC RESPONSES OF THE UTERINE CIRCULATION

The blood vessels of the nonpregnant uterus respond similarly to those of any other muscular
organ with the exception of their unique reactivity to estrogenic stimulation, their response to local
anesthetic agents, and, possibly, their response to prostaglandins (Table 1). During pregnancy, the blood
vessels supplying the placenta progressively dilate, achieving a state in which minimal or no further
acute dilatation can occur.24 Therefore, stimuli which evoke vasodilatation in the nonpregnant uterus
are ineffective after definitive placentation has occurred. However, the placental vessels retain their
ability to vasoconstrict as in the nonpregnant state. Since PBF approximates 80% to 90% of total UBF
at term pregnancy, total uterine vascular responses will appear as those of the placental vessels. This
point is often misinterpreted, and one must remember that the responses of the nonplacental vessels are
the same whether pregnancy is present or not.
The hemochorial structure of the human placenta adds a unique factor to those that normally
control blood flow in other vascular beds. That is, blood traverses the spiral arteries to enter the
swamplike intervillous space, perfuses the fetal villi, and then returns to the general circulation by
many collecting veins in the basal plate. Effectively, blood leaves normal vascular channels to circulate
in a new extravascular space grafted onto the uterus for the duration of pregnancy. Since the
intervillous space lies within the uterine cavity and since the placenta is a flexible structure, pressure
generated by the contracting myometrium will be transmitted equally to the amniotic cavity and the
intervillous space. Thus, a factor extraneous to usual vascular control, myometrial activity, can change
intervillous space pressure and influence PBF by its effects on perfusion pressure. A schematic
representation of blood flow to the non-placental tissues and to a single cotyledon is shown in Figure 4,
along with the formulas pertinent to the control of each. It should be noted that these formulas are only
applications of Ohm's law to these individual cardiovascular situations.

I (Flow) = E (Perfusion Pressure)

R (Vascular Resistance)

The perfusion pressure delivering blood to nonplacental tissues is the difference between uterine
arterial and venous blood pressures. However, the perfusion pressure delivering blood to the
intervillous space is the difference between uterine arterial blood pressure and the intervillous space
pressure. The latter is best approximated by amniotic fluid pressure (IUP). In a muscular organ,
resistance factors will include resistance from reactivity of vascular smooth muscle, or intrinsic
resistance (Ri), and the squeeze imparted to blood vessels as they traverse the contracting myometrium,
or extrinsic resistance (Re). It should be evident then that uterine contractions can affect PBF by two
mechanisms: by increasing Re and by reducing placental perfusion pressure.
In clinical practice, three major characteristics of placental vascular control are important.
These include the relationship between perfusion pressure and flow, the responses of the spiral arteries
to vasoactive stimuli, and the effects of myometrial contractions. In addition, the unique effects of local
anesthetic agents must be appreciated.

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PRESSURE-FLOW RELATIONSHIP

When one observes changes in UBF secondary to reductions in perfusion pressure during
myome-trial quiescence, a straight-line relationship with a slope of one can be developed (Fig. 5). This
reflects the widely dilated nature of the placental vasculature and indicates that PBF will decrease
almost in identical proportion to the decrease in perfusion pressure. Since uterine venous pressure is
quite constant under most circumstances, changes in systemic blood pressure (MBP) may be used to
approximate PBF changes. That is, a 25% decrease in mean arterial pressure would be expected to
cause a 25% decrease in PBF. Such measurements should be made in the lateral decubitus position,
however, since pressure of the gravid uterus on the aorta alone has been shown to decrease blood
pressure in the pelvic area below that observed in the brachial artery.

RESPONSES TO VASOACTIVE STIMULI

Since the spiral arteries approach maximum dilatation in the resting state, vasodilator agents
or stimuli have little or no effect even though receptors for such agents are present. However, the
smooth muscles of these vessels are exquisitely sensitive to vasoconstrictor agents or stimuli, more so
than most other peripheral vascular beds (Fig. 6). This means that although MPB may increase in
response to stimulation by a peripherally acting vasopressor drug such as phenylephrine, the
proportionate increase in placental vascular resistance (Ri) is SO much greater that the net effect is a
marked decrease in PBF. Such differences in vasoconstrictor sensitivity must be considered whenever a
vasopressor drug is indicated. Use of a more centrally acting drug such as ephedrine, although causing
a small amount of placental vasoconstriction, will result in a proportionately greater improvement in
MBP with an absolute increase in PBF.

MYOMETRIAL CONTRACTIONS

Acting by the two mechanisms discussed above, increasing Re and decreasing perfusion
pressure, myometrial contractions decrease PBF in direct proportion to the intensity and duration of
each contraction. The relationship is so precise that a tracing of intrauterine pressure is almost an exact
inverse image of PBF (Fig. 7). Increasing the frequency of contractions decreases PBF during a given
unit of time by decreasing the duration of myometrial diastole, that time when PBF is at homeostatic
levels. In addition, should intercontraction tonus be elevated, as in a placental abruption,
intercontraction PBF will be proportionately reduced. Radioangiographic studies in subhuman primates
and women show that during the acme of myometrial contractions of average intensity, PBF ceases.25
It is evident then that labor is inherently stressful to the fetus, since the mean amount of PBF perfusing
the fetal villi per given period of time progressively decreases as the frequency and intensity of uterine
contractions increase.

LOCAL ANESTHETIC AGENTS

These drugs may exert effects on a vascular bed directly, as after inadvertent intravascular
injection, and indirectly, as a result of paralysis of autonomic nerves that maintain normal vascular
tonus. In most organs, intravascular injections have no significant effects on vascular resistance.
However, the uterine and placental vasculatures respond to such stimuli with significant
vasoconstriction. In addition, the myometrium is variably stimulated by such drugs (Fig. 8). Alone or
together, these responses diminish PBF. Following paracervical block anesthesia administered during
labor, a delayed fetal bradycardia may occur. The best hypothesis to explain the fetal response is that
local anesthetic agents are injected close to the uterine arteries and that because of their excellent
penetrance, they cross the arterial walls to cause their uterine effects decreasing PBF and causing fetal
hypoxia.

65
CLINICAL APPLICATIONS
We have seen that all physiologic, pathologic, and iatrogenic stimuli usually decrease PBF and
that we have no practical means of increasing PBF above homeostatic levels. Therefore, to optimize the
fetal environment, the clinical goal must be to prevent, minimize, or reverse these adverse effects. In
addition, the effects of any dynamic stimulus must always be interpreted on the background of the
adequacy of the homeostatic levels of PBF prior to the stimulus. A theoretical depiction of this
background based primarily on oxygen delivery is shown in Figure 9 and will serve to illustrate the
interplay of homeostatic and dynamic factors.

LABOR

The effects of labor on PBF at three different levels of prelabor homeostasis are illustrated in
Figure 10. This shows mean PBF at four levels of uterine activity and assumes cessation of intervillous
space flow for 30 seconds of a 45-second contraction and 45 seconds of a 60-second contraction.
Whereas a fetus beginning labor at optimal maternal PBF levels is never jeopardized with respect to
oxygen delivery even during a tumultuous labor, that fetus whose mother had suboptimal prelabor PBF
could withstand average labor patterns but would have been depressed at birth or possibly stillborn had
tumultuous labor occurred. It should be obvious in the third case that without any prelabor safety
factor, even the mildest of uterine contractions would be sufficient to cause fetal compromise. This
latter category probably describes the circumstances when a positive contraction stress test is evoked.

REGIONAL ANESTHESIA

Epidural or spinal anesthesia may cause maternal hypotension by paralysis of sympathetic

nerves, peripheral vasodilatation, peripheral pooling, and reduced cardiac return of blood. Since the
placental vasculature is normally widely dilated, sympathetic nerve paralysis would have no effect on
these vessels. We have then a clinical example of the pressure-flow experiment, and an x percent
decrease in MBP would cause an x percent reduction in PBF. This response is illustrated in Figure 11,
along with two methods of treating the hypotension: vasopressor drugs and volume replacement. While
each restores normotension, their effects on PBF are radically different. Predictably from the preceding
discussion, the peripherally acting agent phenylephrine caused no sustained increase in UBF since the
degree of induced placental vasoconstriction far exceeded the rise in MBP. Treatment of the underlying
pathophysiology, a discrepancy between the capacity and the volume of the vascular system, with
volume replacement simultaneously restored MBP and UBF to normal. Sometimes, however, volume
replacement is ineffective and a vasopressor agent must be used. Figure 12 illustrates the more
favorable PBF effects that can be obtained by the use of centrally acting agents and the critical
difference this choice may make depending on the amount of pre-existing reserve PBF.

HEMORRHAGE

Following a bleed of 10% to 15% of circulating blood volume, MBP usually is maintained
within normal limits primarily by peripheral vasoconstriction. The placental vasculature will participate
in this generalized vasoconstriction with a reduction in PBF. With further blood loss, the limits of
compensation are exceeded and hypotension occurs, adding an additional factor to reduce PBF. If mean
blood pressure is decreased 25%, then PBF will be decreased 25% by the pressure-flow mechanism
alone plus an additional decrease from the increased intrinsic vascular resistance. These predictable
responses are confirmed experimentally in Figure 13. As with hypotension induced by a regional
anesthetic block, therapy directed at the underlying problem, volume loss, will improve MBP and PBF
simultaneously, and vasopressor agents should be used only as a last resort.

66
INHIBITION OF LABOR

The b-adrenergic drugs used to inhibit labor act by their relaxing effect on myometrial
contractility. The central and peripheral effects of these agents cause varying degrees of maternal
tachycardia, peripheral vasodilatation, and hypotension. Since the placental vessels are widely dilated
normally, no further vasodilatation can occur and we have another clinical example of the pressure-
flow experiment, PBF varying in direct proportion to changes in MBP. An example of the interplay of
the myometrial and systemic effects of isoxsuprine on PBF in a patient in active labor is shown in
Figure 14. During isoxsuprine therapy, uterine contractions almost ceased and systemic blood pressure
progressively decreased, causing a similar baseline reduction in PBF (Fig. 14A). Prudently, isoxsuprine
was stopped when MBP was halved although the fetal heart rate was still normal. While MBP and PBF
were still at low levels, occurrence of a strong uterine contraction further decreased PBF, causing fetal
bradycardia (Fig. 14B). The wrong decision for proper management was made at this point due to a
failure to recognize that hypotension alone was not stressing the fetus. Rather it was the additional PBF
decreases associated with uterine contractions. Proper management would have been to allow normal
uterine contractions to recur gradually, anticipating that by that time, MBP and PBF would be back to
homeostatic levels. As it occurred, oxytocic stimulation initially caused a sustained contraction that
although of low intensity was sufficient to keep PBF at jeopardy levels despite the progressive increase
in MBP. As a more normal myome-trial contractile pattern evolved, the cessation of PBF during
contractions continued to evoke deceleration patterns (Fig. 14C) until MBP and PBF rose to normal
intercontraction levels (Fig. 14D). Fortunately in this patient, homeostatic PBF was within the normal
range, so while transient fetal hypoxemic episodes occurred, the safety factor was adequate to permit
normal fetal survival.

HYPERTENSIVE STATES

There is considerable evidence that toxemia of pregnancy and chronic cardiovascular-renal

diseases are associated with suboptimal levels of homeostatic PBF.26 Presumably, mechanisms
responsible for the normal dilatation of spiral arteries supplying the placenta are compromised or
inhibited during the definitive placentation process and its subsequent maturation. This could result in
spiral arteries with a capacity for further acute dilation or in vessels with walls immobilized by an
atherotic process so that further dilation could not occur. In both instances, one would expect that the
slope of the pressure-flow curve would be lowered, decreasing progressively as the severity of disease
increases. Therefore, an x percent reduction in perfusion pressure would cause a less than x percent
decrease in PBF (Fig. 15). Theoretically, an autoregulatory curve is possible that would further
minimize PBF decreases during reductions in MBP, but most morphologic studies augur against such
vascular reactivity. Irrespective of these considerations, hydralazine, a nonspecific vascular smooth
muscle relaxant, is frequently used to control life-threatening maternal hypertension. Since we cannot
measure homeostatic PBF and since the effect of hydralazine on the toxemic placental vasculature is
unknown at present, prudent clinical management dictates that we must assume the least favorable
effects. Those would be a decrease in PBF as MBP decreases according to the pressure-flow
relationship and no vasodilatation of the spiral arteries. The end point of therapy should be a tolerable
MBP of 150/90 and normal fetal heart rate patterns. This implies constant fetal monitoring during
therapy and a gradual MBP reduction to prevent undesirable blood pressure and therefore PBF levels.
Failure to observe these tenets may cause fetal compromise as illustrated in Figure 16. In both patients,
intrauterine growth retardation was present, presupposing significant reductions in homeostatic PBF. In
both patients, maternal hypertension was overtreated sufficiently to lower PBF to levels that evoked
severe fetal distress and necessitated cesarean section. It should be noted in the first illustration that the
reduction in MBP alone compromised the fetus. In the second illustration, MBP was reduced less but
the added presence of uterine contractions reduced PBF to fetal jeopardy levels.

UNUSUAL PROBLEMS

67
 The physician must cope constantly with human errors. Figure 17 illustrates one such problem
occurring in a normal laboring woman who accidentally received an injection of methylergonovine
maleate (Methergine) prescribed for a post-partum patient. Ergotrates cause a sustained increase in
myometrial tonus plus or minus superimposed rhythmic contractile patterns. Following the Methergine
injection, intercontraction tonus progressively rose with an obligatory inverse PBF response, and fetal
bradycardia ensued. Recalling the relaxing effect of epinephrine on the myometrium from b-adrenergic
stimulation, the physician prescribed such therapy. Uterine hypercontractility was reduced, but the
placental vasculature responded with vasoconstriction. The net effect of therapy was a decrease in PBF
and persistence of fetal bradycardia. To properly manipulate PBF, the physician must assess the
pathophysiology of each given circumstance and then apply the principles of placental vascular control
to optimize fetal environment. As one reviews this record, the status of the fetus appeared to be
improving and only close observation was indicated. Had the fetus evidenced a deteriorating condition,
specific therapy in the form of a myometrial-relaxing general anesthetic agent such as halothane would
have been indicated. The use of a b-adrenergic agonist such as ritodrine has been recommended in this
situation but is theoretically a less optimal choice. Halothane should be a more predictable myometrial
relaxant, and therapeutic levels would be achieved more rapidly without the development of
confounding variables such as maternal hypotension.

Sociologic considerations
With increased public awareness of physical fitness and the effects of environmental stimuli
on well-being, the obstetrician must broaden his awareness to fetomaternal responses as well. Since the
effects on PBF of only a few such stimuli have been studied, most comments in this area must be
speculative. Two of these stimuli, cigarette smoking and exercise, are addressed in this chapter.
Cigarette smoking increases blood levels of nicotine and carbon monoxide. The latter
decreases the oxygen-carrying capacity of maternal blood, limiting the amount of oxygen available for
placental transfer. Nicotine, a stimulant of autonomic ganglia, apparently mediates its effects by the
release of catecholamines, since maternal blood epinephrine and norepinephrine levels are increased
and since direct infusions of nicotine into the uterine artery cause no change in UBF.15 When nicotine
is administered intravenously to gravid sheep, low doses (125mg/min) cause no effect on UBF,27 while
relatively high doses (1.0 to 1.5 mg/min) evoke significant UBF reductions.15 Presumably, at a given
threshold level of nicotine, sufficient catecholamines are released to increase placental vascular
resistance and decrease PBF. One must be cautious in applying such data from sheep to women since
the effects of intravenous nicotine rather than smoking per se have been measured and since factors
such as habituation and tolerance to chronic stimulation have not been evaluated. However,
observations of pregnancy outcome in smoking mothers suggest a subtle, long-term, dose-related
reduction in fetal growth. Therefore, it is reasonable to presume that smoking causes a qualitative long-
term reduction in PBF and that smoking should be stopped or decreased during pregnancy, especially if
high-risk conditions exist.
The effects of maternal exercise on UBF and the fetus have been observed only in the ovine
species. In general, these studies indicate that mild to moderate exercise for up to 60 minutes is well
tolerated by the fetus. When exercise was continued to the point of extreme fatigue or exhaustion,
maternal respiratory alkalosis and decreased UBF occurred with reductions in fetal arterial oxygen
tensions. In one study, fetal oxygen uptake was maintained during a 28% decrease in UBF by a 56%
increase in oxygen extraction across the uterus.28 In another study on only four ewes, moderate to
heavy daily exercise for 30 minutes during the last half of gestation resulted in lambs of low birth
weight.29
Although the data are fragmentary, they support a fairly consistent response pattern. Cardiac
output increases during exercise in response to the increasing metabolic demands of contracting
muscles. The splanchnic and presumably the uterine circulations continue at only slightly reduced
levels as long as this need can be met adequately. If peripheral demands exceed the cardiac capability,
further splanchnic vasoconstriction and peripheral shunting will occur. During moderate to heavy
exercise, the data suggest a degree of PBF reduction that is offset by increased oxygen extraction.
During pregnancy, PBF will be affected by pre-pregnancy conditioning, the increased pregnancy load
on the heart, and the degree of exercise. In addition, the effect on the fetus will be determined by the

68
adequacy of homeostatic PBF. Recommendations regarding exercise during pregnancy must take all of
these factors into consideration. It would be unwise for a nonjogger to begin such activity during
pregnancy. Continuation of an established exercise program during early pregnancy with a gradual
reduction in activity as the pregnancy load on the heart increases is logical. In the presence of
conditions thought to reduce homeostatic PBF, perhaps all but mild exercise should be prohibited.

Overview
Uterine vascular adaptations to pregnancy require local blood vessels to dilate some tenfold to
20-fold to meet the requirements of the fetoplacental unit and the enlarging myometrial mass. While
the spiral arterioles that perfuse the intervillous space probably undergo the greatest morphologic
changes during this process, dilatation of supply arteries from the major uterine vessels down through
the radial arteries is also critical to meet the downstream demand. For example, the middle uterine
artery of a yearling ewe prior to conception is thin walled to the point of translucency and is no greater
than 2 mm in diameter. At term pregnancy, the arterial walls are much thickened, with diameters
between 8 and 10 mm. After the first pregnancy, the nonpregnant uterine artery retains its thickened
wall with diameters of approximately 3 mm, and an experienced observer can easily tell from the
appearance of the artery alone whether the ewe has been pregnant previously or not. Similar changes
must occur in arteries within the uterus as well. There is increasing evidence that inadequate
development of the uterine vasculatures to meet pregnancy requirements may be determined primarily
during the definitive placentation process and that PBF so compromised may lead to the development
of toxemia of pregnancy.30 The high frequency of toxemia during the initial pregnancy, that requiring
the greatest uterine vascular adaptations, is consistent. If this theory is correct, then an improved
understanding of the placentation process becomes critical to subsequent pregnancy performance and
management. Our knowledge of the dynamic factors controlling PBF, although by no means complete,
is adequate to guide rational management. However, we desperately need methods to evaluate precisely
the adequacy of homeostatic PBF. Optimally these would be noninvasive techniques; therefore,
application of ultrasonic methods seems to offer the most fruitful area for research. Development of
such technology would permit increased understanding of PBF changes throughout pregnancy,
knowledge that may delineate critical developmental times and an appreciation of normal as well as
pathologic mechanisms.

DOPPLER VELOCIMETRY
Ultrasound technology has evolved from only producing images of the pregnancy to now
include methods for measurement of both maternal and fetal circulatory functions. The phenomenon of
Doppler shift of ultrasonic echoes forms the technical basis for acquisition of information on the
maternal–fetal hemodynamic circulations.
Johann Christian Doppler was an Austrian physicist who taught in Prague during the mid-1800s
(White, 1982). He suggested that when a sound source (for example, red blood cells in fetal umbilical
circulation) is moving relative to an observer (for example, an ultrasound transducer), the perceived
pitch will vary from the true pitch. In accordance with the Doppler shift principle, echoes returning
from moving structures are altered in frequency and the amount of shift is directly proportional to the
velocity of the moving structure. The frequencies of echoes returning from structures moving toward
the transducer are higher than the frequency originally transmitted by the transducer. In contrast, the
frequencies of echoes returning from structures moving away from the transducer are lower. The
primary uses of these Doppler echo shifts in obstetrics have been to detect and measure blood flow. The
sound of moving blood cells within the vasculature generates an effective Doppler shift, which serves
as the basis of Doppler velocimetry studies of maternal and fetal circulations. There are two methods of
estimating circulatory hemodynamics: (1) direct measurement of the volume of blood flow and (2)
indirect estimation of flow velocity using waveform analysis.

Determination of Blood Volume Flow

Doppler-shifted sound frequencies depend on a number of factors (Fig. 44–13 ):

69
 In this equation, fo is the original frequency of the ultrasound beam (in obstetrical imaging this
is usually 3 to 5 MHz), v is the velocity of blood cells in the vessel studied, q is the incident angle
(angle of insonance) between the ultrasound beam and the vessel, and c is the speed of sound (in tissue,
equal to 1540 m/sec). The cosine remains close to 1 as long as the angle is kept low, but at higher
angles of insonance, especially those more than 60 degrees, considerable error in measurement is
introduced.
The equation in Figure 44–13 includes a factor (v) for the velocity of blood in the vessel
studied. To solve for v, and to thus estimate the velocity of red blood cells, the following equation is
used:

Because volume flow (mL/min) is simply velocity times cross-sectional area of the blood vessel
(area equals pi times the square of the radius), it is possible to calculate volume flow by measuring the
blood vessel diameter using ultrasound. However, there are several technical difficulties with
measurement of vessel diameters. For example, the vessels are dynamic with changing diameters
during the cardiac cycle. The many technical difficulties inherent in Doppler blood volume flow
measurements result in high error rates for this methodology. Estimates of error up to 15 percent have
been reported with the most careful attention to methodology (Gill, 1985) and errors up to 50 percent
are not uncommon (Burns, 1987). Because of these methodological problems, blood volume flow
measurements have been largely abandoned in clinical applications (Low, 1991).
WAVEFORM ANALYSIS OF BLOOD VELOCITY
Waveform Analysis of Blood Velocity. From the foregoing, the errors encountered in volume
flow estimation may be profound. Thus indirect indices of flow have been developed that might
provide useful information about flow without engendering excessive errors. These indices are
independent of the angle of insonation and do not require measurement of the diameter of the vessel.
Perhaps the most simple of these indices to compute is the systolic–diastolic ratio, or S–D ratio
(Fig. 44–14 ). The maximal systolic shift is divided by the end-diastolic shift. This may be measured
from the maternal uterine or fetal umbilical artery. In both vessels, the index gradually decreases as
gestation progresses. Because of the low diastolic velocities seen in more central fetal vessels, such as
the descending aorta, the S–D ratio is not useful elsewhere in the fetal circulation.
Similar in ease of calculation is the Pourcelot index, or the resistance index (Fig. 44–14 ). To
calculate this index, the difference in systolic and diastolic shifts is divided by the systolic value ([S -
D]/S, also expressed as 1 - [D/S]). This ratio is also applicable only to the umbilical and the uterine
arteries, and low diastolic values limit its usefulness in the fetal aorta or other central vessels.
Of the widely used indices, the most complicated to measure is the pulsatility index (Fig. 44–
14 ). It requires a digitized waveform for calculating the mean of the maximal frequencies represented.
Because of the mean value in the denominator, this index can be computed using flow data from the
fetal descending aorta without encountering excessive variation caused with division by small numbers
as with the other two indices. Doppler arterial waveforms in nonpregnant humans are characterized by
high systolic velocity and little or no diastolic velocity. Exceptions are the carotid and cerebral vessels,
which have continuous diastolic blood flow seen on waveform analysis. During pregnancy, maternal
and fetal vessels perfusing the placenta assume waveforms indicative of continuous diastolic flow.
Doppler waveforms of vessels have been described in a variety of ways, but all are based upon
the relationship between systole and diastole. The most common measurements are some variation of
the S–D ratio. These measurements are intended to relate peak flow at systole to that at end-diastole,
and the ratio is calculated from the height of the systolic and diastolic peaks.
Waveforms with a high flow in diastole accompany low downstream vessel impedance. In
contrast, waveforms with little diastolic flow, or reversed flow, are seen when vascular impedance
downstream is abnormally high (e.g., placental insufficiency). Figure 44–15 illustrates several of the
vessels in which S–D ratios have been studied, as well as the corresponding S–D waveforms for blood
velocity in these vessels. Blood flow velocity has also been studied in the umbilical vein and fetal
cerebral circulation.

70
Techniques for Specific Vessels
UTERINE AND ARCUATE ARTERIES
Placental circulation is characterized by high volume flow, with an extensive diastolic
component. Uterine blood flow increases from 50 mL/min shortly after conception, to 500 to 750
mL/min by term. Its Doppler waveform shape is unique, characterized by high diastolic velocities
similar to those in systole and highly turbulent flow, with many different velocities apparent (Fig. 44–
15 ). With this degree of diastolic flow, indices decrease as term approaches—that is, diastolic velocity
increases with advancing gestation. A failure of this pattern to appear or the presence of a notch in the
waveform at end-systole has been reported with fetal growth retardation (Schulman and associates,
1986).
The external iliac arteries are easily identified because they do not have diastolic flow (Fig. 46–
15 ). For other vessels, any absence of late-diastolic flow, or reversal of flow, is considered abnormal.
As mentioned, the various indices applied to umbilical artery analysis decrease during the latter phases
of normal pregnancy (Hendricks and co-workers, 1989).
UMBILICAL VEIN
The intra-abdominal portion of the umbilical vein is relatively straight and the flow tends to be
constant rather than pulsating. Therefore, the umbilical vein is a reasonable vessel for measuring
volume flow rather than indexed flow. Umbilical vein blood-flow measurements range from 108 to 153
mL/kg per minute with decreasing flows as gestation advances (Gerson and co-workers, 1987).
FETAL DESCENDING AORTA
The fetal descending aorta receives the majority of right-ventricular output via the ductus
arteriosus, while the majority of left-ventricular output supplies the fetal head and upper arms. Flow in
the descending aorta is highly pulsatile, with little diastolic flow. The straight course of the aorta also
makes it amenable to volume flow studies. Waveform flow measurement is limited to the pulsatility
index because of the lack of diastolic flow. Measurements of fetal descending aorta blood flow range
from 185 to 246 mL/kg per minute (Eik-Nes and co-workers, 1982; Griffin and associates, 1985).
CAROTID ARTERY AND CEREBRAL BLOOD FLOW
Attempts have been made to measure fetal cerebral blood flow to explain why fetal head growth
is spared in some forms of fetal growth retardation. If there is preferential blood flow to the brain, there
should be maintenance, or even augmentation, of cerebral blood flow. Currently, the carotid arteries are
the only cerebral vessels that can be identified reliably, but they are too narrow to measure accurately.
Thus, preliminary findings are interpreted with caution since it is not always possible to be sure that
comparable vessels are studied.

Fetal Cardiac Function

The measurement of fetal cardiac function may have immediate clinical importance as well as
research implications.
CARDIAC OUTPUT
Doppler techniques that measure fetal cardiac output are extremely difficult to apply because of
fetal movement and technical factors discussed above. However, with combined use of two-
dimensional ultrasound and Doppler echocardiography, initial results appear promising. Reed and
colleagues (1986a, 1986b) reported that mean right-ventricular output was 307 mL/kg per minute and
left-ventricular output was 232 mL/kg per minute (right to left ventricular output ratio 55:45). DeSmedt
and associates (1987) reported a slightly higher value for combined ventricular output.
DUCTUS ARTERIOSUS
Functional applications of fetal Doppler echocardiography have been reported by Huhta and
colleagues (1987). They assessed ductus arteriosus constriction in both lamb and human fetuses.
Reversible ductal constriction was observed in three fetuses whose mothers received indomethacin for
treatment of preterm labor. Such changes were not observed in 25 normal pregnancies.

71
FETAL ARRHYTHMIAS
Using a variety of techniques, fetal cardiac arrhythmias can be diagnosed and appropriately
treated. In most instances these diagnostic techniques consist of two-dimensional real-time ultrasound
examinations to identify cardiac anatomy and accurate placement of M-mode echocardiographic
beams. M-mode echocardiography appears to be useful, especially in diagnosing fetal cardiac
arrhythmias and in assessing ventricular wall function. Functional outputs by atria and ventricles as
well as timing of these events can be measured using pulsed-Doppler methods. Reed and associates
(1987) presented evidence of improved (ventricular) cardiac output after conversion of supraventricular
tachycardias to normal sinus rhythms. They also were able to confirm that the Frank–Starling
mechanism (increased diastolic volume results in increased stroke volume) is operative even in the
fetus!

Fetal Well-being
A recurring theme in the potential practical applications of Doppler ultrasound is the search to
distinguish normal from abnormal pregnancies. Of particular interest have been predictions of growth
retardation, fetal hypoxia, and fetal distress. It has also been proposed that abnormal uteroplacental
waveforms may identify women at risk for pregnancy-induced hypertension.
Applications of this technology are discussed in relation to its use in the diagnosis and
management of a variety of pregnancy complications and their management is presented throughout
this book. Doppler velocimetry has been proposed as a method of fetal surveillance, as discussed in
Chapter 43. According to the American College of Obstetricians and Gynecologists (1994), such
surveillance is never required and is regarded as investigational.

TABLE 44–1. SOME INDICATIONS FOR OBSTETRICAL ULTRASONIC EXAMINATIONSa

Evaluation of fetal growth
Vaginal bleeding of undetermined etiology
Determination of fetal presentation
Suspected multiple gestation
Adjunct to amniocentesis
Significant uterine size/clinical dates discrepancy
Pelvic mass
Suspected ectopic pregnancy
Adjunct to special procedures
Suspected fetal death
Suspected uterine abnormality
Intrauterine contraceptive device localization
Biophysical evaluation of fetal well-being
Observation of intrapartum events
Suspected polyhydramnios or oligohydramnios
Suspected abruptio placentae
Adjunct to external version from breech to vertex presentation
Estimation of fetal weight and/or presentation in preterm prematurely ruptured
membranes and/or preterm labor
Abnormal serum alpha-fetoprotein value
Follow-up observation of identified fetal anomaly
Follow-up evaluation of placental location for identified placenta previa
History of previous congenital anomaly
Serial evaluation of fetal growth in multifetal gestation
Evaluation of fetal condition in late registrants for prenatal care

aEstimation of gestational age for women with uncertain clinical dates, or verification of dates for
women
who are to undergo scheduled elective repeat cesarean delivery, indicated induction of labor, or other
elective pregnancy termination.
Adapted from National Institutes of Health (1984).

72
TABLE 44–2. COMPONENTS OF BASIC ULTRASOUND EXAMINATION ACCORDING TO
TRIMESTER OF PREGNANCY
First Trimester Second and Third Trimester
1. Gestational sac location 1. Fetal number
2. Embryo identification 2. Presentation
3. Crown–rump length 3. Fetal heart motion
4. Fetal heart motion 4. Placental location
5. Fetal number 5. Amnionic fluid volume
6. Uterus and adnexal evaluation 6. Gestational age
7. Survey of fetal anatomy
8. Evaluation for maternal pelvic masses

Modified from American College of Obstetricians and Gynecologists (1993).

TABLE 44–4. PREDICTED MENSTRUAL AGE (MA) IN WEEKS FROM CROWN–RUMP

LENGTH (CRL) MEASUREMENTS (IN CENTIMETERS)a

CRL MA CRL MA CRL MA CRL MA CRL MA CRL MA

0.2 5.7 2.2 8.9 4.2 11.1 6.2 12.6 8.2 14.2 10.2 16.1
0.3 5.9 2.3 9.0 4.3 11.2 6.3 12.7 8.3 14.2 10.3 16.2
0.4 6.1 2.4 9.1 4.4 11.2 6.4 12.8 8.4 14.3 10.4 16.3
0.5 6.2 2.5 9.2 4.5 11.3 6.5 12.8 8.5 14.4 10.5 16.4
0.6 6.4 2.6 9.4 4.6 11.4 6.6 12.9 8.6 14.5 10.6 16.5
0.7 6.6 2.7 9.5 4.7 11.5 6.7 13.0 8.7 14.6 10.7 16.6
0.8 6.7 2.8 9.6 4.8 11.6 6.8 13.1 8.8 14.7 10.8 16.7
0.9 6.9 2.9 9.7 4.9 11.7 6.9 13.1 8.9 14.8 10.9 16.8
1.0 7.2 3.0 9.9 5.0 11.7 7.0 13.2 9.0 14.9 11.0 16.9
1.1 7.2 3.1 10.0 5.1 11.8 7.1 13.3 9.1 15.0 11.1 17.0
1.2 7.4 3.2 10.1 5.2 11.9 7.2 13.4 9.2 15.1 11.2 17.1
1.3 7.5 3.3 10.2 5.3 12.0 7.3 13.4 9.3 15.2 11.3 17.2
1.4 7.7 3.4 10.3 5.4 12.0 7.4 13.5 9.4 15.3 11.4 17.3
1.5 7.9 3.5 10.4 5.5 12.1 7.5 13.6 9.5 15.3 11.5 17.4
1.6 8.0 3.6 10.5 5.6 12.2 7.6 13.7 9.6 15.4 11.6 17.5
1.7 8.1 3.7 10.6 5.7 12.3 7.7 13.8 9.7 15.5 11.7 17.6
1.8 8.3 3.8 10.7 5.8 12.3 7.8 13.8 9.8 15.6 11.8 17.7
1.9 8.4 3.9 10.8 5.9 12.4 7.9 13.9 9.9 15.7 11.9 17.8
2.0 8.6 4.0 10.9 6.0 12.5 8.0 14.0 10.0 15.9 12.0 17.9
2.1 8.7 4.1 11.0 6.1 12.6 8.1 14.1 10.1 16.0 12.1 18.0
aThe 95% interval is ±8% of the predicted age.
Reproduced, with permission, from Hadlock FP, Shah YP, Kanon DJ, Lindsey JF. Fetal crown-rump
length: reevaluation of relation to menstrual age (5–18 weeks) with high-resolution real-time US.
Radiology. 182:501, 1992.

TABLE 44–5. AVERAGE PREDICTED FETAL MEASUREMENTS AT SPECIFIC MENSTRUAL

AGES

Menstrual Age (wk) Biparietal Diameter (cm) Head Circumference (cm) Abdominal
Circumference (cm) Femur Length (cm)
12.0 1.7 6.8 4.6 0.7
12.5 1.9 7.5 5.3 0.9
13.0 2.1 8.2 6.0 1.1
13.5 2.3 8.9 6.7 1.2

73
14.0 2.5 9.7 7.3 1.4
14.5 2.7 10.4 8.0 1.6
15.0 2.9 11.0 8.6 1.7
15.5 3.1 11.7 9.3 1.9
16.0 3.2 12.4 9.9 2.0
16.5 3.4 13.1 10.6 2.2
17.0 3.5 13.8 11.2 2.4
17.5 3.8 14.4 11.9 2.5
18.0 3.9 15.1 12.5 2.7
18.5 4.1 15.8 13.1 2.8
19.0 4.3 16.4 13.7 3.0
19.5 4.5 17.0 14.4 3.1
20.0 4.6 17.7 15.0 3.3
20.5 4.8 18.3 15.6 3.4
21.0 5.0 18.9 16.2 3.5
21.5 5.1 19.5 16.8 3.7
22.0 5.3 20.1 17.4 3.8
22.5 5.5 20.7 17.9 4.0
23.0 5.6 21.3 18.5 4.1
23.5 5.8 21.9 19.1 4.2
24.0 5.9 22.4 19.7 4.4
24.5 6.1 23.0 20.2 4.5
25.0 6.2 23.5 20.8 4.6
25.5 6.4 24.1 21.3 4.7
26.0 6.5 24.6 21.9 4.9
26.5 6.7 25.1 22.4 5.0
27.0 6.8 25.6 23.0 5.1
27.5 6.9 26.1 23.5 5.2
28.0 7.1 26.6 24.0 5.4
28.5 7.2 27.1 24.6 5.5
29.0 7.3 27.5 25.1 5.6
29.5 7.5 28.0 25.6 5.7
30.0 7.6 28.4 26.1 5.8
30.5 7.7 28.8 26.6 5.9
31.0 7.8 29.3 27.1 6.0
31.5 7.9 29.7 27.6 6.1
32.0 8.1 30.1 28.1 6.2
32.5 8.2 30.4 28.6 6.3
33.0 8.3 30.8 29.1 6.4
33.5 8.4 31.2 29.5 6.5
34.0 8.5 31.5 30.0 6.6
34.5 8.6 31.8 30.5 6.7
35.0 8.7 32.2 30.9 6.8
35.5 8.8 32.5 31.4 6.9
36.0 8.9 32.8 31.8 7.0
36.5 8.9 33.0 32.3 7.1
37.0 9.0 33.3 32.7 7.2
37.5 9.1 33.5 33.2 7.3
38.0 9.2 33.8 33.6 7.4
38.5 9.2 34.0 34.0 7.4
39.0 9.3 34.2 34.4 7.5
39.5 9.4 34.4 34.8 7.6
40.0 9.4 34.6 35.3 7.7
Reproduced, with permission, from Hadlock FP, Deter RL, Harrist RB, Park SK. Estimating fetal age:
Computer-assisted analysis of multiple fetal growth parameters. Radiology. 152:497, 1984.

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TABLE 44–6. SOME LIMITATIONS OF THE 18- TO 20-WEEK ULTRASONIC STUDY

Structural review incomplete

Face—lips
Heart—ventricular development, leaflets
Genitalia—some fetuses
Peripheral vessels—too small
Uncertain significance
Umbilical artery velocimetry
Subjectively decreased amnionic fluid
Low-lying placenta
Unusual placental anatomy
Deficit not yet manifest
Late obstructive defects—hydrocephaly, hydronephrosis, gastrointestinal atresia
Intermittent/incomplete anomaly
Fetal growth disturbances
Fetal behavior disorders
Evolution of maternal status
Therapy limited to extrauterine regimens
Reprinted from Harman C. The routine 18 to 20 week ultrasound scan. In James DK, Steer PJ Weiner
CP, Gonik B, eds. High Risk Pregnancy Management and Options. 1994:664, by permission of the
publisher WB Saunders Company Limited, London.

75
 ULTRASOUND BIOEFFECTS FOR THE
PERINATOLOGIST
Safety
Safety. Although there is a theoretical risk for tissue damage at high intensities from the
effects of heat and cavitation, no independently confirmed biological effects in mammalian tissue have
been demonstrated in the frequency range of medical ultrasound (American Institute of Ultrasound in
Medicine, 1991). In the low-intensity range of gray-scale imaging, no fetal risks have been
demonstrated in over 25 years of use.
Recent advances in technology have introduced Doppler shift imaging coupled to gray-scale
imaging in order to localize spectral wave forms and superimpose color or intensity mapping. Higher-
energy intensities are used with duplex Doppler imaging. For this reason, the Food and Drug
Administration (FDA) arbitrarily limited ultrasound energy exposure to less than 94 mW/cm2 during
fetal imaging. Currently, the preferred measures of ultrasound output are the mechanical index (MI)
and thermal index (TI), rather than intensity in mW/cm2. In the case of fetal evaluation, Doppler has
been approved for use in the evaluation of the cardiac anomalies and in the setting of fetal growth
restriction (Scoutt and associates, 1990).

In the past few decades, ultrasound has become the primary imaging procedure for an
increasing number of conditions. Ultrasound imaging is an integral part of the practice of obstetrics,
gynecology, radiology, cardiology, neurology and neurosurgery, pediatrics, gastroenterology, urology,
angiology, surgery, and internal medicine. In obstetrics, ultrasound is increasingly used for applications
such as the assessment of gestational age and the diagnosis of placenta previa, multiple gestations, fetal
growth retardation, and certain fetal structural abnormalities such as spina bifida and hydrocephalus.
Diagnostic ultrasound has also proved useful in antenatal surgery for fetal diseases.

There is no doubt that a spectacular improvement in ultrasound imaging quality contributed to

the rapid increase in its use as a diagnostic tool. Also, the introduction of the linear array real-time
scanner in the 1970s led to a significant increase in the amount of ultrasound imaging performed during
pregnancy. Recent advances in real-time scanners include the introduction of duplex systems, which
combine real-time imaging with pulsed (including color) Doppler ultrasound. These systems made
possible the measurement of fetal and uteroplacental blood flow. Information on that flow may become
one of the most important obstetric applications of diagnostic ultrasound.

As a result of these advances, a rapidly increasing number of pregnant women have been
exposed to ultrasound. Over a decade ago, about 40% of all pregnant women in the United States had
undergone routine scanning.1 However, there are reasons to believe that today this number is
significantly higher: the corresponding rate of ultrasound exposure in most western European countries
is now about 80%; in West Germany, virtually all babies are exposed to ultrasound in utero.

Because there is potential for the fetus to have long-term adverse effects from exposure to
ultrasound,2 it is more than relevant to ask, "How safe is ultrasound?" It is well established that under
certain conditions ultrasound can lead to undesirable side effects.3,4,5,6,7 Therefore, it is unrealistic to
expect that the answer to this question can be a simple "yes" or "no." Rather, the question to be
answered should be, "Is diagnostic ultrasound safe as presently used in clinical practice?"

The main goal of this chapter is to summarize the available knowledge regarding whether
ultrasound energy produces bioeffects at the levels currently used with commercial diagnostic
equipment.

It must be stressed at the outset of this review that, to date, no evidence has been found of
harmful effects of ultrasound in humans at clinically used exposure levels. However, new applications

76
of and new advances in diagnostic imaging regularly prompt discussions on its safety and prudent use.
Common to these discussions is that they call for avoidance of unnecessary exposure.7,8,9,10 Also of
concern is that although there is no reason to believe that there are risks related to ultrasonic exposure,
there are many inexpensive ultrasonic scanners throughout the world. Therefore, there is an ongoing
need to disseminate the knowledge of interactions between ultrasound energy and biologic tissue and to
identify the potential conditions for bioeffects.7,9,11

It is appropriate to note that any modern literature search on ultrasonically induced bioeffects
will result in a list containing hundreds of papers and reports on the topic. Because the literature on this
subject is enormous, only those papers that are considered to be relevant for this review are discussed
here. In particular, attention is focused on data pertaining to mammalian tissue. Those readers who are
interested in reviewing all data available are referred to excellent textbooks12,13 or to several
comprehensive reports.3,4,5,6,7,11,14,15,16,17

Any informed discussion on bioeffects requires a basic understanding of the physical

parameters involved and their relation to the observed effect. More specifically, the relation between
the magnitude of the effect and the magnitude of the characteristic parameters of the ultrasound agent
should be known. In addition, it is important to determine whether the effect will give rise to any
concern. Otherwise, the significance of the experimental outcome can be misinterpreted easily and may
lead to meaningless conclusions regarding the outcome's relevance to clinical practice.

To facilitate an understanding of these relations and to judge the significance of the findings
reported in the literature properly, it is appropriate to start with a brief review of the relevant ultrasound
parameters and the physical mechanisms of interaction between ultrasound and biologic tissue. This is
followed by a summary of the range of acoustic output levels produced by the currently used clinical
diagnostic machines and a succinct discussion of recent developments in the regulatory area. Briefly,
these developments permit manufacturers to introduce a real-time on-screen display involving Thermal
and Mechanical or Cavitational Index (TI and MI, respectively). These indices inform the user of the
potential for ultrasonically induced bioeffects. Understanding the implications of such an on-system
display is of vital importance for practitioners, including physicians, sonographers, and other allied
health personnel applying ultrasound energy to patients. This is because the displayed information
about the potential of bioeffects requires practitioners to make a direct decision as to the risks and
benefits associated with the given clinical examination.7,8,9,10,11,12,13,14,15,16,17,18

Next, a survey of the literature on biologic effects is given. As already noted, the biologic
experiments that are discussed were carefully selected and limited to those that bear the closest
resemblance to clinical exposure conditions. Special attention is given to human epidemiology studies;
limitations and deficiencies of the current research on ultrasonically induced bioeffects are also
discussed.

The conclusions focus on a critical summary of the current evidence on risks associated with
ultrasonic exposure in diagnostic clinical examinations, including several relevant statements on in
vivo mammalian bioeffects and safety by the American Institute of Ultrasound in Medicine (AIUM)
Bioeffects Committee.17

PHYSICAL MECHANISMS OF INTERACTION BETWEEN

ULTRASOUND AND BIOLOGIC TISSUE BIOLOGIC TISSUE
It is widely accepted that there are two basic mechanisms, namely, thermal and nonthermal, by
which ultrasound is known to affect biologic materials.3,12,13,14,17,18,19,20 Nonthermal mechanisms
include cavitational and noncavitational effects, which are associated with certain mechanical aspects
of the acoustic or ultrasonic field. These aspects can be described in terms of second-order phenomena,

77
such as radiation pressure, radiation force, radiation torque, and acoustic streaming, and are
comprehensively reviewed in other sources.19,20

Because the data on second-order phenomena were obtained primarily by studying in vitro
systems, and because their biologic significance is not immediately clear, attention is focused on
thermal and cavitational phenomena. The following succinct description of these mechanisms should
be satisfactory for the purpose of this chapter.

THERMAL MECHANISM

This mechanism is associated with the absorption of acoustic energy by tissue and the
generation of heat. The thermal mechanism appears to be the best understood, and analytic models have
been developed to predict the possible temperature elevation in tissue.18 These models relate acoustic
energy to the associated temperature increase, provided that absorption coefficients for the tissues
considered are known. A brief description of the physical and physiologic variables that play a role in
the generation of this temperature elevation follows.

As an ultrasound beam traverses tissue layers, the rate of energy deposition is determined by
the factors defined by the operational characteristics of the imaging system and the physical parameters
of the tissue being imaged. The system's operating characteristics are functions of the imaging and/or
Doppler mode being used, as well as of the focal characteristics of the transducer and its frequency. As
an example of the way these characteristics influence energy transfer, one can note the difference in
energy distribution between scanned modes such as B-mode and the pulsed-wave (PW) Doppler. More
specifically, B-mode energy is distributed over a large volume, whereas in unscanned modes, such as
PW Doppler, the acoustic energy is aimed along a single line. Similarly, a highly focused transducer
has the potential for a highly concentrated energy deposition, whereas weakly focused transducers tend
to spread the energy over larger volumes. Whether or not energy is deposited in a given tissue volume
is determined by that tissue's absorption characteristics, which may vary significantly depending on the
organ considered. For example, there is almost no absorption in liquids such as amniotic fluid, blood,
and urine. However, an adult bone absorbs about 60% to 80% of the acoustic energy impinging on it.18
With fetal bone, there is a wide variation in absorptive behavior, depending on the degree of
ossification. The clinical situation of greatest interest as far as thermal effects are concerned is a fetus
in utero with an ossified bone structure and a mother with a thin abdominal wall. In such a case there is
little attenuation of acoustic energy because of the thin layer of intervening maternal tissue, yet there is
a high degree of absorption associated with the fetal bone.18

Local generation of heat per second in a volume of 1 cm3 can be calculated from the
following expression:

W = 0.23 · a(f) · I

where a(f) is the absorption coefficient in dB/cm (in most tissues this coefficient is
proportional to the frequency), and I is the local average intensity per time unit in W/cm2 (a more
rigorous definition of intensity is given in the next section). The absorption coefficient is defined by the
tissue characteristics, whereas the in situ intensity is determined by both the imaging system and the
attenuation of the overlying tissues. The relation between the intensity in a given tissue layer and its
absorption deserves a brief discussion here. A highly focused beam whose focal point is in amniotic
fluid will not cause significant heating of the fluid simply because the absorption level of the fluid is
low. In this situation, the a(f) of the above equation is relatively low, whereas the I has a relatively high
value. The same beam with its very high focal intensity will cause a significant temperature rise if it
impinges on ossified bone, which has an a(f) value that is significantly higher than that of amniotic
fluid.

Another important determinant of local heating involves the degree of attenuation in tissue
layers in front of the point of interest. An increased amount of attenuation in the overlying tissues

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decreases the energy available for conversion into heat. Thus, the use of fetal Doppler through a thick
abdominal wall is less likely to cause a significant temperature increase than are examinations
involving patients with thin abdominal walls.

Although the above discussion has concentrated on heat sources, there are at least two
mechanisms of heat loss. Blood perfusion is an efficient mechanism for heat removal. In fact, the
designers of hyperthermia systems have significant difficulties with it.21 The degree of blood perfusion
varies between the tissue types: among the best perfused organs are the kidneys, heart, and brain,
whereas bone and resting muscle are among the least perfused.22 Another cooling mechanism is due to
heat conduction. The degree of thermal conductivity is relatively uniform among the tissues and is
fairly close to that of water, with the exception of bone, which is highly conductive, and fat, which is a
poor thermal conductor.22

There seems to be an agreement that an in situ temperature rise to or above 41°C is considered
hazardous in fetal exposures because it may lead to undesired effects. A more detailed discussion of the
recent AIUM recommendations concerning possible thermal mechanism -related bioeffects is given in
the closing section of this chapter.17

Experimental studies indicate that intact mammalian systems (in vivo) do not show a
significant rise in temperature when exposed to pulsed imaging equipment.3,12,17 However, the
recently developed peripheral vessel pulsed and continuous-wave (CW) Doppler equipment, when used
for a relatively long time (1 -10 min), may be an exception.17,23 Therefore, the Doppler system should
be used with care, especially during the recently developed applications in which Doppler is used for
the study of blood velocities in the umbilical cord and the fetus.

CAVITATIONAL MECHANISM

The term cavitation refers to phenomena associated with the vibration and motion dynamics of
small gaseous bodies when exposed to an ultrasound field.12,17,20 In the first approximation, these
gaseous bodies are treated as spherical cavities (microbubbles) about 1 mm in diameter. Such gaseous
bodies may expand because of "rectified diffusion"24,25 until their radius grows to the magnitude at
which mechanical resonance takes place.

Near the frequency of mechanical resonance, the vibration amplitude of the bubble wall is
large and may range up to 100 times the value of the radius at equilibrium (i.e., when the sound field is
turned off).26 If the bubble does not collapse during the ultrasound exposure, the condition is referred
to as stable cavitation, in contrast to inertial (collapse) cavitation (formerly known as transient
cavitation5), during which the vibration amplitude of the bubble wall increases so much that the bubble
implodes. This implosion generates highly localized shock waves and is also associated with extremely
high local temperatures (up to 10,000°K).27 In addition to the temperature elevation, the implosion
results in the generation of free radicals such as hydroxyl radicals and hydrogen. These radicals are
very active and may lead to some undesired biologic changes, such as spontaneous biochemical
reactions within the tissue.

In this context it is worthwhile to point out that lung hemorrhage has been observed in mice
after exposure to ultrasound waves with relatively low peak pressures of 1 to 2 MPa. More specifically,
cavitation-related events were reported as a mechanism leading to lesions in the lung tissue of adult
mice.28 The hemorrhage of lung tissue in mice occurred as a result of exposure to 1-MHz, 10-ms
pulses of about 1 MPa pressure amplitude. Also, the lung tissue damage was observed in the lungs of
monkeys exposed to 3.7 MPa using a commercial diagnostic ultrasound imaging device operating at
the maximum output in combined pulsed and color Doppler mode.29 This is of interest because
monkey represents a biologic model closely resembling human. This suggests that the alveoli may act
as cavitation nuclei and that caution should be exercised in cases in which the ultrasound interacts with
lung tissue. Although only a limited number of primates were used in the study, these results are
important because lung hemorrhage was observed at clinically relevant exposure conditions. Also,

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although these results have not yet been independently confirmed, this study suggests an increased
potential risk when frequent cardiac examinations are performed in the neonates. It is appropriate to
point out here that certain tissues may be more prone to cavitation-like events than others. Thus, no
kidney hemorrhage in mice was observed at peak positive pressures of 9 to 10 MPa and negative peak
pressure amplitudes of 4 to 5 MPa at frequencies of 1.2 and 3.8 MHz.30 Thus, it appears that in kidney
tissue there are no nuclei to sustain a gas body.

The bioeffects observed in the study by Tarrantal and Canfield29 and the study by Carstensen
and colleagues30 are also relevant to the situation in which the fetus undergoes prolonged exposure to
ultrasound in an early stage of pregnancy. Therefore, the ultrasound examination time should be
minimized, consistent with the requested diagnostic information.

Inertial cavitation leading to severe tissue hemorrhage also has been experimentally observed
during therapeutic treatment of the kidney using an extracorporeal shock-wave lithotriptor.31

Although of only peripheral interest to the present discussion, it should be recognized that a
sufficiently high negative peak amplitude of the ultrasonic wave can cause severe damage to the tissue.
A typical pulse generated by a lithotriptor is shown in Figure 1. The negative pressure amplitude of the
typical lithotriptor pulse (see Fig. 1) may be of the same order of magnitude as the corresponding
pressure amplitude of the pulses used in diagnostic ultrasound (see Acoustic Output Levels).

During stable cavitation, the vibration amplitude of the bubble wall may set up microflow
(microstreaming). The theory of microstreaming is well developed and is well described by Nyborg.32
The theory predicts that the microstreaming can generate shear stress that acts on adjacent bodies such
as cell membranes.5,32,33 If the shear stress is sufficiently large, it may cause breakage of the cell
membrane.32,33 It may be argued that cell membrane breakage can also happen during exercise such
as jogging. Nevertheless, the breakage, even if unimportant from a biologic point of view, occurs
because of the body's response to an external agent, and therefore it should not be totally dismissed.
Although phenomena resembling stable cavitation have been reported in in vivo experiments, it appears
that they occurred under exposure conditions not directly relevant to diagnostic imaging.28

ULTRASOUND FIELD PARAMETERS

As already mentioned, interpreting the data on the safety of ultrasound requires some
knowledge of the basic terminology of key ultrasound field parameters, such as acoustic pressure or
intensity. Thus, before the review of bioeffects observed, it is essential to briefly clarify the
nomenclature used in ultrasonic exposimetry and to introduce acoustic field parameters relevant to
ultrasound bioeffects.34

It is common practice to relate the bioeffects of ultrasound to intensity. Therefore, it is

important to distinguish between spatial peak, spatial average, temporal (or time) peak, and temporal
average intensities (Fig. 2). In addition, spatial peak, pulse average intensity (ISpPa) is often used. In
fact, an ISpPa intensity of 190 W/cm2 constitutes a limit for temporal peak output levels of diagnostic
ultrasound equipment.35

Spatial peak (Sp) intensity is defined as the maximum point intensity measured in the field of
a radiating transducer; spatial average (Sa) intensity is the average of the intensity across a given area;
temporal peak (Tp) intensity is the maximum intensity for a given time interval; and time average (Ta)
intensity is the average of the intensity for a given time interval. Rigorous definitions of these
parameters can be found in several publications.34,35

It should be pointed out that a combination of spatial and temporal intensities is needed to
relate an observed bioeffect to ultrasound field parameters. Thus, the widely known AIUM
publication17 refers to the spatial peak, temporal average (SpTa) intensity. Also, it should be noted that
although bioeffects are conventionally related to the acoustic intensity or I (units: W/cm2), the field

80
parameter currently gaining attention is acoustic pressure P (units: pascals or Pa; 105 Pa = 1 bar ~ 1
atmosphere), because it is often the primary parameter measured. Moreover, knowledge of peak
negative pressure amplitude is needed to determine the value of the MI (see The Output Display
Standard).

All intensities are found by analyzing the pressure -time waveform recorded at the prescribed
position in the ultrasound field in water, the beam profile taken at this position, and the measurements
of focal distance and imaging frequency.35 The acoustic pressure -time waveform (Fig. 3), if measured
with a calibrated receiver, contains the information required to determine most of the ultrasound
exposure parameters. Thus, the waveform contains information about the working frequency of the
imaging transducer, positive and negative peak pressures, the pressure gradient, and possible nonlinear
propagation phenomena.36,37

From the analysis of the waveform, characteristic times (such as effective pulse duration time)
and ultrasound field intensity parameters (such as Im [instantaneous maximum],35 SpTp [spatial peak,
temporal peak], SpTa [spatial peak, temporal average], SaTa [spatial average, temporal average], and
SpPa [spatial peak, pulse average] intensities) can be determined.3,34,35

In addition to these intensities, the beam pattern distribution, total acoustic power (W), pulse
repetition rate (PRR), and imaging frequency are needed to adequately determine ultrasound field
parameters. All of these parameters can be determined by using calibrated miniature ultrasonic
hydrophone probes. The probes are made of piezoelectric polymer such as polyvinylidene fluoride
(PVDF) and exhibit excellent acoustic properties. The most common designs use either the original
hoop membrane approach or the needle-type construction.38 When properly designed, the probes have
proved suitable as reference hydrophones with good spatial and temporal resolution. With their flat (to
within ± 1.5 dB) frequency response and uniformity of voltage sensitivity to beyond 15 MHz, they are
uniquely suited to the measurement and characterization of ultrasound fields and acoustic sources. In
addition, the characteristic features of the probes, such as well behaved, generally predictable
directivity patterns, excellent linearity over a wide range of pressures (up to 100 MPa in the biomedical
ultrasonics range of frequencies), and long-term stability, make them suitable for the comprehensive
characterization of both pulsed and continuous-wave ultrasonic fields. These hydrophones are pressure-
sensitive devices; therefore, conversion of the pressure into intensity units is usually done under the
tacit assumption that the plane wave approximation holds (i.e., that intensity is proportional to the
square of the pressure amplitude and inversely proportional to the product of density and sound
velocity).

Calculation of different intensities is fairly complex and involves squaring and integration of
the pressure - time waveform. The steps needed to determine intensities and other relevant exposure
parameters from the analysis of the waveform are shown in Figure 3. Detailed algorithms that allow
SpPa, SpTa, and Im intensities to be calculated in water and in situ can be found in the 510(k) Guide
for Measuring and Reporting the Acoustic Output of Diagnostic Ultrasound Medical Devices.35

An additional ultrasound field parameter to be determined is the total acoustic power

generated by the imaging transducer. Calculation of the total power requires knowledge of the beam
profile taken in the plane corresponding to the focal distance at which the waveform of Figure 3A was
recorded.

Complete ultrasound dosimetry also requires information on exposure time, including dwell
time. The dwell time is defined as the time during which the ultrasound beam (more specifically its
focal zone) remains at the same site of the body in usual clinical practice.

Each expression of intensity mentioned above serves a different purpose.34 Briefly, the ISpPa
is a measure of the ultrasound energy associated with a single pulse, and Im intensity characterizes the
maximum instantaneous energy in the period of the pulse duration. The ISpTa corresponds to the
energy averaged over a period of time and is proportional to the PRR. Although a typical imaging
system has a PRR (also referred to as pulse repetition frequency) on the order of 1 kHz, a PRR as high

81
as 20 kHz may be used in blood flow velocity measurements using Doppler devices. The rationale for
determining peak negative and peak positive pressure amplitudes and the intensity parameters shown in
Figure 3 is their potential for producing bioeffects. A comprehensive discussion of this issue is given in
the article by Nyborg and Wu.34

ACOUSTIC OUTPUT LEVELS

Once the definitions of the different acoustic intensities are known, the data available on the
acoustic output of ultrasonic equipment for imaging and Doppler applications can be summarized. The
acoustic output levels of the diagnostic devices quoted here were compiled from recently published
data and are listed in Table 1, Table 2 and Table 3.39 The Doppler instruments measured included CW
Doppler units for cardiovascular investigations, fetal monitors, stand-alone pulsed Doppler equipment,
color Doppler, and duplex scanners working in Doppler mode, all in the frequency range of 2 to 8
MHz. Measurements were carried out in water and revealed that pulsed Doppler equipment could
generate SpTa intensities that exceeded 100 mW/cm2, with a maximum of 4520 mW/cm2.39 (The
maximum SpPa intensity for pulsed Doppler equipment was about 770 W/cm2).39

The output of some CW cardiovascular Doppler devices produced intensity levels on the order
of 850 mW/cm2, whereas fetal monitoring equipment intensities were on the order of 30 mW/cm2.
Table 1 and Table 2 compile the highest intensities measured at the output of pulsed and CW Doppler
equipment, respectively. Table 3 summarizes maximum output levels encountered at the output of
clinical pulsed echo equipment.

THE OUTPUT DISPLAY STANDARD

Before a review of the clinical evidence for ultrasonically induced bioeffects can take place, it
is important to briefly discuss the clinical implications of the recently implemented Output Display
Standard (ODS).7,17,35 As a result of discussions that involved the Food and Drug Administration
(FDA), the AIUM, and the National Electrical Manufacturers Association (NEMA), in 1994 the FDA
revised its guidance on diagnostic ultrasound 510(k) submissions to allow the use of the MI in place of
the ISpPa in determining substantial equivalence of devices. This revision assumes that on-system
displays17 of numerical indices, including MI and TI, will inform the user about the potential for either
thermal or nonthermal bioeffects associated with the actual examination settings of the imaging system.
This enables the clinician to increase acoustic power output beyond the existing FDA guidelines when
clinically warranted. Before the 1994 FDA revision, such an increase was not possible. The maximum
available acoustic output was limited by the manufacturer's software, which would not allow the output
to exceed FDA guidelines for maximum exposure. It must be stressed that with the implementation of
the ODS, diagnostic ultrasound systems can have a higher output limit. With the higher limits comes
the potential for increased risk to the patient, so the clinician must make a careful risk/benefit analysis.
Therefore, the purpose of the ODS is to help the clinician implement the ALARA (as low as reasonably
achievable) principle and minimize the potential for bioeffects.

In the following pages, the thermal and mechanical indices are defined and the potential for
added diagnostic and clinical benefits is briefly discussed. Additional comments on the indices are
given in the Conclusions section. A more comprehensive treatment of the different tissue models
(including homogeneous tissue, soft tissue, and bone tissue) used in the development of the indices is
found in Medical Ultrasound Safety,7 Bioeffects and Safety of Diagnostic Ultrasound,17 and the article
by Thomenius.18

The TI, which should be displayed during all unscanning equipment operations (i.e., M-mode,
CW, and PW Doppler, as well as color Doppler), is considered to be best suited as a predictor of
possible thermal effects. The MI has been developed as an indicator of the potential cavitation-like
phenomena related to B-mode operation. The TI is defined as: TI = W0/Wdeg, where W0 is the

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acoustic power output of the probe under a given operating condition and Wdeg is the estimated
acoustic power output necessary to raise the target tissue temperature by 1°C.

The MI is considered to be a suitable predictor of possible cavitation-like phenomena. MI is

equal to (rr.3/f0)1/2, where rr.3 is the maximum derated value of peak rarefactional or negative pressure
amplitude and f0 is the center transducer frequency. It should be noted that whereas the rr.3 values
associated with lithotriptors (see Fig. 1) and diagnostic ultrasound instruments often are of the same
order of magnitude, the increased potential for the occurrence of cavitation with lithotriptors is
associated with their lower frequency content of the shock waves (about 0.5 -2 MHz).

BIOEFFECTS
In general, the bioeffects literature can be divided into two classes: one based on the
epidemiology of the large number of ultrasound examinations performed both clinically and as
laboratory experiments, and another in which a causal relation between bioeffects and the applied
acoustic energy is developed. Both classes are discussed below.

EFFECTS OF ULTRASOUND ON MAMMALIAN TISSUES IN VIVO

Simple in vitro models, such as cells, are often used in the search for biologic effects to gain
an understanding of the possible mechanisms of interaction between ultrasound and biologic tissue.
The results of the research on biologic effects in nonmammalian species, such as insects, amphibians,
and avians, indicate that studies on these relatively simple organisms are helpful in understanding the
mechanisms of interaction between ultrasound and biologic systems.15 However, from the point of
view of this work, studies of mammalian species are of more relevance. The examples chosen for the
present discussion pertain mainly to in vivo insonation of mammalian tissue and include exposure
conditions at clinically relevant frequencies. Most of the bioeffects studies were performed on small
rodents, such as mice or rats. Although these animals constitute a fairly inexpensive model for in vivo
bioeffects studies, the extrapolation of experimental results to humans is not immediately obvious. A
very comprehensive review of the effects of ultrasound on mammalian development was prepared by
Sikov.16 He evaluated bioeffects depending on gestational age and thus attempted to extract
information on the relation between exposure parameters and stage of development at exposure.

Because this approach seems useful for drawing some conclusions about the adverse effects of
diagnostic ultrasound in prenatal practice, it was adapted in the following discussion of bioeffects
findings.

EARLY STAGE. Several researchers studied the influence of ultrasound exposure in the period
before implantation. In the CW studies, Takeuchi and co-workers40 used pregnant rats exposed to a
2.5-MHz ultrasound field on the second and third day of gestation, at spatial average intensities of 150
mW/cm2. No increase in prenatal mortality was found. Similarly, no increase in the rate of postnatal
malformation was found after 20-minute exposures. These results are not surprising in view of the fact
that absorption in the embryonic tissue is lower than that of the surrounding tissue. Therefore, it is
likely that more heat was generated in the vicinity of the embryo than in the embryo tissue itself.

Stolzenberg and associates41 exposed pregnant mice to 2-MHz of CW ultrasound in the first 3
days of gestation. A 1-inch (about 25 mm) planar source transducer was used, and the spatial average
intensity was determined to be 1 W/cm2. A decreased uninterrupted pregnancy rate was noted after
exposure for 5 minutes on the third day and after exposure for 200 seconds on day zero. Also, a
reduction in fetal weight after delivery was observed at thresholds corresponding to exposure for 100
and 200 seconds on day zero and 200 and 400 seconds on the first day. In another series of studies,42
ultrasound exposure led to damage of maternal tissue, which was reflected in increased mortality,
decreased weight gain, and paralysis of the pups.

83
 Thus, it appears that in vivo exposure to CW ultrasound at spatial average intensities below 1
W/cm2 does not affect embryos at the early stage of gestation. However, limited data suggest that
levels of ultrasound of 1 W/cm2 may lead to undesirable changes in maternal tissue.

The application of ultrasound in guided oocyte aspiration for in vitro fertilization and embryo
transfer is rapidly growing. Therefore, the recent studies aimed at determining the interaction between
ultrasound exposure and successful fertilization are included in this discussion.43,44 In general, the
clinically available data on ultrasound exposure of oocytes during meiosis are confusing. Although
some researchers reported a deleterious effect on the fertility of patients undergoing artificial
insemination (they claimed a reduction in the cumulative rate of pregnancy),45 others claimed an
increase in the success rate, allowing ultrasound monitoring of follicular growth.46

An attempt to clarify this ambiguity was described by Mahadevan and colleagues.47 Their
study sought to determine how oocytes obtained under ultrasound guidance affected the pregnancy rate.
The results obtained at 3.5 MHz suggest that exposure of human oocytes to ultrasonic waves during the
different phases of meiosis does not significantly influence the developmental potential of the in vitro
fertilized embryos. Unfortunately, except for ultrasound frequency, these researchers did not give any
of the relevant exposure parameters discussed earlier.

ORGANOGENESIS. McClain and associates48 exposed rats to 10 mW/cm2 CW Doppler

ultrasound for up to 2 hours at frequencies of 2.25 and 2.5 MHz. The fetuses were examined on day 20,
and no consistent increase in mortality was observed, nor did the authors detect any other
abnormalities.

Stolzenberg and co-workers41 reported a decrease in the uninterrupted pregnancy rate of mice
exposed between days 6 and 8 to a spatial average intensity of 1 W/cm2. They reported statistically
significant fetal weight reductions for exposures longer than 140 seconds. More evidence of the
possibility of ultrasonically producing embryolethal effects during organogenesis has been
described.49,50,51,52 Sikov and colleagues49,50,51,52 exposed an exteriorized rat uterus to three
frequencies (0.8, 2, and 3.2 MHz) at day 9 and evaluated the offspring at day 20. The exposure was
performed at different intensity levels, with exposure times at 5 or 15 minutes. No effect on fetal
weight was observed, even at spatial average intensities as high as 30 W/cm2, but prenatal mortality at
15 to 20 W/cm2 (spatial average) clearly increased with increasing exposure time. The cause of this
was ascribed to a thermal mechanism.

FETAL BONE HEATING. Several researchers have investigated exposure conditions in which
the ultrasound energy was impinging on a bone embedded in tissue with relatively little absorption or
attenuation. This situation is particularly relevant in obstetrics, because the developing fetus is exposed
to diagnostic ultrasound. Carstensen and associates53 insonified exposed mouse skulls that had
thermocouples implanted. Both adult and young mice were used. The results were reproducible, with
the older mice yielding a steady temperature rise of 5.6 ± 0.3°C with a focal intensity of 1.5 W/cm2. In
the first 15 seconds of ultrasound application, the temperature rose to about 75% of the final value.
Comparison of these results with the theoretic predictions obtained from an appropriate tissue model18
indicated an agreement to within 20%; however, the theoretic transient response indicated the
possibility of a considerably faster rate of temperature increase--the 75% was predicted to be achieved
within 5 seconds of exposure. These results indicate that there may be a reason for concern, especially
with the rate of temperature increase. Also, at this rate of heating, the exposure time should be limited
to about 1 minute.18 If the temperature increase had been, for example, 7°C, the exposure time
necessary for a bioeffect to occur would have been 15 seconds. It cannot be ruled out that during an
actual examination, the acoustic beam might be held stationary for such a period.

POSTNATAL DEVELOPMENT. Equally important in determining the safety of diagnostic

ultrasound is knowing the influence of prenatal ultrasound exposure on postnatal development. In a
carefully devised study,54 pregnant rodents were exposed to 500 mW/cm2 spatial average intensity at
2-MHz ultrasound for 1 to 3 minutes, or to 1 W/cm2 spatial average intensity for 40 to 60 seconds. No

84
fetal mortality was observed; however, a weight decrease in the pups delivered was observed after
exposure to 0.5 W/cm2 for 180 seconds.

In another study, the effects of prenatal ultrasound exposure on adult offspring behavior in the
Wistar rat were investigated.55 The animals were exposed on days 15 through 17 and on 19 of
gestation to a 5-MHz, 1-kHz pulse repetition rate and intensities (ISpTp) of 500 and 1500 W/cm2. The
total exposure time was 35 minutes. Two hundred seventy-eight offspring were subjected on postnatal
day 60 to two of four well-established behavioral tests. The animals were tested in random order within
sexes. The results showed no consistent dose-related alterations in adult behavior due to prenatal fetal
exposure.

Vorhees and co-workers56 used a unique approach to study the possible teratogenic effects of
ultrasound exposure. They eliminated the need for anesthesia (and therefore the possible complications
caused by forced restraint) by training the rats to remain immobile during the ultrasound exposure. The
animals were exposed to 0.1, 2, or 30.0 W/cm2 (ISpTa), 3 MHz CW, for about 15 min/day on days 4
through 19 of gestation. No dose-dependent changes in various maternal parameters, the incidence of
malformation, or fetal weight were observed. In a follow-up study, Vorhees and colleagues57 exposed
rats to these levels of ultrasound for 10 minutes on gestational days 4 through 20. Although they did not
observe exposure-related alterations in maternal parameters, offspring survival and growth, or neonatal
psychophysiologic parameters, changes did occur in offspring adult behavior, in locomotor activity, and
in two measures of the multiple-T water maze test performance at the highest dosage level.

In the studies aimed at determining the effects of ultrasound exposure on uteroplacental

function, ter Haar and co-workers58 found that a spatial peak intensity of 2 W/cm2 at 3 MHz caused an
exteriorized uterus to increase in frequency of contraction, which lasted for about 4 minutes after the
ultrasound was turned off. They reported no increase in temperature and thus ascribed the increased
rate of contractions to an unspecified nonthermal mechanism.

Placental function during ultrasound exposure was investigated by Kelman and

associates.59,60,61 In their experiments they insonified the placenta of a guinea pig with 2.5 MHz of
ultrasound at different intensity levels and in both pulsed and CW modes. Functional changes were
observed after 10 minutes of exposure at SpTp intensities of 30 W/cm2 in pulsed mode (pulse length,
10 ms; PRR, 1 kHz) and SpTa intensities of 28 to 46 W/cm2 in the CW mode.

Again, it appears that at sufficiently high intensity levels, ultrasound can affect vitelline blood
flow and lead to increased uterine contractility and changes in placental function. However, the
exposure levels far exceed those present in the clinical environment. Murrils and associates62 found
that fetal Doppler monitoring did not influence fetal activity, which would be an indication of
ultrasound effects on the perinatal nervous system.

BIOEFFECTS RELATED TO HYPERTHERMIA

The evidence above indicates that there is a teratogenic effect of heat on the prenatal
development of mammalian tissues. Experiments with cultured rat embryos stressed the importance of
ambient temperature; no bioeffects were observed when embryos were exposed to pulsed ultrasound
for 15 minutes at ISpTa levels of 1.2 W/cm2.63 However, the same experiment repeated with the
temperature elevated 1.5°C above normal (40°C) resulted in retardation of head growth. Although the
outcome of this experiment cannot immediately be extrapolated to humans, it indicates that ultrasound
exposure of a febrile pregnant patient under certain conditions might constitute an increased risk for
potential bioeffects.

There are relatively few papers containing diagnostically relevant information on this subject;
therefore, it is appropriate to draw attention here to a recent survey.64 This survey established that no
thermal bioeffects were observed at temperature elevations of 39°C, regardless of how long the
ultrasound exposure lasts. However, for each increasing degree of temperature elevation, to stay within

85
safety limits, the duration of ultrasound examination must be reduced by a factor of four. More
specifically, the review indicated that the maximum safe duration for a temperature of 43°C is 1
minute, and for 42°C it is 4 minutes. Similarly, at 41°C the exposure time may be increased to 16
minutes, and at 40°C the duration of examination may be as long as 64 minutes. Based on the data
available, the survey concluded that if the maximum temperature rise during the ultrasound exposure is
kept less than 2°C, any biologic effect (in a febrile patient) is highly unlikely. It is possible to express
the relation between the exposure time required for a bioeffect to occur and the associated TI, namely, t
= 4 < (6 -TI). Thus, for a TI of 6, the exposure time should be limited to 1 minute. Similarly, a TI of 4
means that the exposure time should be less than 16 minutes (see Appendix).

Recent findings indicating that the ultrasound imaging transducer may act as a substantial heat
source (Duck FA, unpublished observations) are also of interest. The temperature at a clinically
operated Doppler transducer was reported to increase by 10°C when the Doppler was applied to skin
with a standard coupling gel. Although tissue heating from the transducer is most likely limited to the
tissue volume in the immediate vicinity of the transducer, this effect should be kept in mind for
ultrasound examinations in which an endocavity (e.g., endovaginal) transducer is used, or when
performing contact scanning of the neonatal brain or in ophthalmologic applications.

BIOEFFECTS RELATED TO CAVITATION

A few relevant papers reporting lung hemorrhage in mice and in monkeys caused by
cavitation-like phenomena have already been discussed under Cavitational Mechanism.28,29 These
papers describe significant biologic effects associated with gas body activation. The effects were
produced in vivo in mammalian lung tissue in small rodents (mice) and in primates (monkeys). The
bioeffects were observed at pressure amplitudes and pulse durations representative of those currently
encountered at the output of diagnostic ultrasound equipment, particularly when used in pulsed Doppler
mode. As previously noted, the results described in those papers are important for the present
discussion because they led to a modification of the AIUM statement on "In Vivo Mammalian
Bioeffects." The statement, which was renamed "Non-Human Mammalian In Vivo Biological Effects,"
emphasizes the importance of the MI.17

Recent data presented in the article by Dalecki and colleagues65 indicate that, in general,
threshold pressures increase with increasing frequency. The thresholds for hemorrhage in the intestine
of adult mice ranged from about 1 MPa at 1 MHz to 3 MPa at 3 MHz (10-ms pulse duration, 100-Hz
repetition rate).

To date there is no evidence that flowing cardiovascular blood will permit cavitation in vivo.
Although there is some indication that microscopic gas bodies may exist in biologic tissue, there is no
evidence that exposure of these bodies to the ultrasound levels similar to those used in clinical
diagnostic practice will cause any significant bioeffects. However, it is conceivable that vibration of
those bodies may introduce cell membrane stresses that can lead to extravasation of blood in lung
tissue.5 This may indicate a need for appropriate modification during cardiovascular examinations and
transesophageal echocardiography.

The above findings indicate that the body regions containing gas volumes are very sensitive to
the potential side effects of ultrasound exposure and that biologic effects can be introduced by using a
commercially available diagnostic imaging system in tissues containing gas volumes. Carefully
designed studies are needed to assess any potential hazards with conditions that are typical for
diagnostic ultrasound. Such hazards may also be associated with ultrasonic contrast agents injected into
the vascular system.

To summarize, the thresholds for confirmed cavitation-induced biologic effects in mammalian

tissues in the diagnostic frequency range of 2 to 8 MHz are above 1 MPa.17 All of the biologic effects
that have been confirmed under diagnostically relevant exposure conditions involve tissues that are
known to contain microscopic gas bodies. For tissues not containing gas (such as the kidney), no

86
damage was observed at peak positive pressures on the order of 10 MPa.30 Lung hemorrhage has been
observed in neonatal and adult mice, rabbits, monkeys, and neonatal swine with diagnostically relevant
ultrasound pressures ranging from 1 to 3 MPa. No damage was observed in the lungs of adult swine at
pressures on the order of 5 MPa (see Appendix).28,29

EPIDEMIOLOGIC STUDIES

The evidence of ultrasonically induced bioeffects in humans is perhaps the most important
information from the clinician's point of view. As pointed out by Ziskin and Petitti,2 "No matter how
many laboratory experiments show a lack of effect from diagnostic ultrasound, it will always be
necessary to study directly its effect in human populations before any definitive statement regarding
risk can be made."

There are extensive reviews of the literature on the epidemiology of human exposure to
ultrasound.1,3,6 As would be expected, the major thrust of these reviews is the assessment of the
possible side effects of ultrasound exposure in utero. This is mainly because most pregnant women are
exposed to ultrasound examination in the early stages of pregnancy and because any harmful effects to
the fetus may last for years to come.

In general, few data pertaining to human ultrasound exposure are available. Some of the
published data are reviewed briefly here. The experiments of O'Brien,66 who observed that in utero
exposure to ultrasound resulted in reduced birthweight in mice, prompted similar studies in humans.
Bakketeig and associates,67 in their randomized, controlled trial, reported that they were unable to find
any effect of ultrasound on birthweight in humans. A similar conclusion was drawn from the earlier
studies on the relation between ultrasound exposure and birthweight.68

Although no fetal structural anomalies were observed in the recent studies performed by Stark
and co-workers68 and Bakketeig and colleagues,67 Stark and associates reported somewhat disturbing
findings in their retrospective follow-up examinations of 425 children exposed to ultrasound in utero
and 381 unexposed children. They reported an increased risk of dyslexia; however, their study suffers
from the fact that the subjects were not selected at random. No evidence has been found that ultrasound
exposure in utero may lead to an increased rate of childhood cancer.69,70 Likewise, no relation
between in utero exposure and children with hearing deficiencies has been determined.68

DEFICIENCIES OF THE BIOEFFECTS STUDIES

The data presented earlier indicate that the exposure of pregnant rodents to CW ultrasound at
sufficiently high intensities during organogenesis can lead to undesirable biologic changes in the
developing fetus. Also, recent evidence has emerged indicating that the body regions containing gas
volumes may be particularly prone to potential side effects when exposed to sufficiently high pressure
amplitudes.28,29 Although the data were carefully selected to include only those studies that can be
readily related to diagnostically relevant exposure conditions, it should be stressed that in most cases
the bioeffects were observed at exposure conditions that were different from those typical of clinical
diagnostic practice. Before 1990, most of the bioeffects observed were ascribed to the thermal
mechanism of interaction between the ultrasound and biologic tissue, but in the past half decade it has
been demonstrated that exposure to ultrasound produced by commercially available diagnostic imaging
equipment can produce nonthermal, cavitation-like bioeffects in the lung tissue of primates.29

Many bioeffects studies describe the effects of whole-body heating, which most likely acts
through a mechanism that is not immediately comparable to ultrasound-induced hyperthermia. Few
studies have been specifically designed to determine threshold values for abnormal embryonic or fetal
development.64 On the basis of the thermal criterion, a diagnostic exposure that produces a maximum
temperature rise of 1.5°C above normal physiologic levels can be used without reservation in clinical
examinations (see Appendix). However, a diagnostic exposure that produces an in situ temperature

87
elevation to or above 41°C for 15 minutes should be considered hazardous to embryonic or fetal
development. Any increase in the tissue temperature will act as a potentiating factor. Therefore,
ultrasound examination in a febrile patient may constitute an additional embryonic and fetal risk.5

The reviews on human exposure clearly indicate that epidemiologic studies and surveys yield
no evidence of adverse effects from diagnostic ultrasound, but they also point out several serious
deficiencies of all the data available. These deficiencies are carefully discussed by Ziskin and Petitti.2

Ziskin and Petitti point out that the available results of epidemiologic studies are based on
about 500,000 patient examinations that were collected from 179 users of clinical ultrasound. However,
the results allow only a fairly cautious statement to be made, namely, that the users overwhelmingly
believe that their experience with diagnostic ultrasound had been safe.

Ziskin and Petitti also note that all clinical studies on the possible harmful effects of
ultrasound exposure to the fetus produced negative results. However, the acoustic outputs of the
diagnostic instruments used were generally not known. In addition, the sample sizes (the number of
patients included in the studies) were limited to a few hundred. In their careful assessment of the
limitations of the epidemiologic studies, Ziskin and Petitti focus on the lack of information or simply
inadequate ultrasound dosimetry. Also, the reasons for the examinations were not clearly stated, and
sparse information is available on the number of examinations and the gestational age at the time of
exposure. In addition, most studies were performed with pulsed ultrasound. As shown in Table 1,
Doppler ultrasound results, in general, in higher values of ISpTa. Ziskin and Petitti suggest that the
existing data on exposure of the fetus in utero are inadequate to conclude that diagnostic ultrasound is
safe at all combinations of dose and period of exposure for both imaging and Doppler devices.

Another point addressed by these researchers is the importance of statistical considerations,

including sample size and statistical level of significance. Because a more thorough treatment of
statistics is beyond the scope of this chapter, it can be simply stated that the larger the sample, the
higher the statistical level of significance that can be achieved. The usefulness of small samples is
extremely limited; studies that use small samples usually have inconclusive results.

In summary, the human studies that have been performed do not preclude the possibility that
adverse effects may be found under certain conditions. The limited data available indicate that no
relation has been found between prenatal exposure to ultrasound and subsequent postnatal changes in
children, but statistical considerations show that minor chemical and behavioral changes, long-term
delayed effects, and certain genetic effects could easily escape detection.2 There is still a need for a
well-designed, randomized clinical study addressing the risk for the fetus exposed in utero.

CONCLUSIONS
In general, the literature describing clinically relevant exposure conditions is rather limited,
and few results, if any (even of experiments in vivo), can be immediately applied or extrapolated to
discussions of clinical safety. The reason for this is the large number of variables that must be
considered, which makes bioeffects experiments difficult to design and perform free from artifacts.
Also, the number of subjects exposed to the ultrasound field is often limited, so the data obtained
cannot be considered statistically significant.2,3 It is worth reiterating that lung hemorrhage was
produced in the lung of a macaque monkey whose chest was exposed to the maximum output level
produced by a commercially available diagnostic scanner.29 The mechanism of injury was determined
to be a nonthermal one; the tissue damage appeared to be caused by gas volumes existing in the lung
tissue. Although these findings were not confirmed by an independent laboratory, they indicate that
caution should be used in diagnostic examinations related to echocardiographic and esophageal
applications.

88
 Results of experiments performed at exposure levels and durations higher than those used in
diagnostic examinations are difficult to extrapolate to human examination conditions. In addition,
reproducibility of the results presents a further limitation: often the bioeffects observed cannot be
confirmed by an independent laboratory. It is conceivable that more uniform requirements regarding
the determination of acoustic output parameters would facilitate comparison of the experiments
between different laboratories.

The current evidence on ultrasonically induced bioeffects in the laboratory setting (with the
possible exception of the results published in the article by Tarrantal and Canfield29 and those pointed
out in the article by Barnett and colleagues5) is not immediately applicable to the clinical situation.
However, it is important to keep in mind that the uncertainties experienced in determining the intensity
levels and the associated exposure conditions do not permit a categorical statement to be made
regarding the unconditional safety of diagnostic ultrasound. It is also important to reiterate that the
available data from both empirical and epidemiologic studies indicate that there is no verified evidence
of adverse effects in patients caused by exposure to diagnostic levels of ultrasound (see Appendix).

Although these findings are consistent with almost three decades of clinical experience, it is
also important to realize that the acoustic exposure levels in the available data may not be
representative of the full range of current fetal exposure (see Table 1, Table 2 and Table 3). As already
indicated, the acoustic outputs of diagnostic instruments have been increasing,17,39 and recent
laboratory studies indicate that tissue damage can occur at the exposure levels produced by
commercially available equipment.5

Acoustic output measurements indicate that the peak rarefactional pressure amplitudes of
some Doppler systems can exceed 4 MPa. Although such pressure amplitudes appear to be sufficient to
cause adverse effects,29 so far no evidence has been presented indicating any pulmonary extravasation
after ultrasound exposure. However, these data indicate that appropriate caution should be exerted
during neonatal examination, because even small amounts of extravasation can be of concern. In
practice, this would require operators to follow the ALARA principle and to use the minimum
transmitting acoustic power necessary to obtain adequate diagnostic data. The continuously updated
display of the TI and MI should be of significant assistance here. As already mentioned, these indices
provide information on the likelihood of an adverse biologic effect occurring from the ultrasound
examination that is currently performed in clinical practice.7 The TI index provides real-time
information indicating the worst-case temperature rise at the actual operating conditions of the imaging
equipment. The MI index indicates the potential for cavitation phenomena to occur. If the predefined
set value is exceeded, indicating the potential for harm, the clinician will be able to make an informed
decision regarding the benefit/risk ratio of the given ultrasound examination. The decision may be
influenced by factors that are not covered in the indices. These factors include consideration of the
imaging site perfusion, patient obesity (which may severely restrict penetration depth), and a possible
reduction in the exposure time by minimizing the duration of examination. A continuously updated on-
screen display of the MI and TI indices is incorporated in recent designs of diagnostic ultrasound
imaging equipment. It is appropriate to note that an output display is not required if the transducer and
the system are not capable of exceeding an MI or TI of 1. However, if the transducer and system are
capable of exceeding an MI or TI of 1, then the system must display values as low as 0.4 to assist the
operator to implement the ALARA principle (see Appendix).7 It should be noted that the MI, which is
defined as a derated (0.3 dB/cm/MHz) peak rarefactional pressure in MPa (rr.3) divided by the square
root of the center frequency in MHz, is not a perfect indicator. Although it simplifies the description of
thresholds for bioeffects in tissues containing stabilized gas bodies, it may underestimate conditions in
situ. Another limitation of the MI is that it describes conditions only at the focus. This may not be the
primary point of interest, for instance in cardiological examinations. In this case, the most common
way for the lung to be exposed during a diagnostic procedure is where the transducer is applied directly
to the chest of the patient. Here, the focal region of the transducer is not within the lung tissue. An in-
depth discussion of which index is most appropriate for a given examination, as well as a careful
discussion of the limitations involved in implementing the ALARA principle with the use of these
indices, is given in the article titled Medical Ultrasound Safety (also see Appendix).7

89
 Overall, the clinical data are reassuring in that no established adverse effects on human
patients exposed to diagnostic ultrasound examinations have been reported. However, the deficiencies
of the data available and the tendency to increase the acoustic output power indicate the need for
carefully planned experiments to provide safety information relevant to medical practice. Knowledge
of the relevant ultrasound field parameters, such as the maximum peak pressure (with regard to both
space and time), working or center frequency, pulse waveform, beam profile, and pulse repetition
frequency, is essential for proper comparison of the experimental results. This knowledge, along with
the actual exposure time, should be included in papers reporting on the biologic effects of ultrasound.

Analysis of the acoustic output data given in the previous sections indicates that the diagnostic
procedure that introduces the greatest concern for thermal bioeffects is the use of PW Doppler in a fetal
examination. Similarly, cavitation or a gas body -related mechanism is associated with B-scan imaging
of the developing fetus.

This chapter concludes with a brief review of official AIUM statements (see Appendix). These
statements were prepared by the AIUM Bioeffects Committee, whose expertise in the field is widely
recognized in the ultrasound community throughout the world. The statements summarize the current
knowledge on the physical mechanisms of interaction between ultrasound and biologic tissue and are
based on both empirical and clinical data. The empirical data were scrutinized to detect possible dose -
response relations regardless of the underlying mechanisms.

The data in the literature allow a fairly comprehensive statement on "Non-Human In Vivo
Biologic Effects," which covers both thermal and nonthermal mechanisms and provides guidelines to
estimate potentially hazardous pressure amplitudes or intensity levels and exposure times.

In conclusion, diagnostic ultrasound has an excellent safety record. The clinical data are
reassuring in that there is no report of damage to human patients from diagnostic ultrasound. However,
it must be emphasized that neither theoretic calculations nor experimental results can yield
unambiguous and definite evidence that fully guarantees the safety of ultrasound diagnostics. Because
diagnostic ultrasound is an extremely powerful tool in the hands of experienced physicians and
sonographers, the final decision regarding the risks and benefits can be made only by the individual
responsible for applying the ultrasound to the patient.

Appendix
The American Institute of Ultrasound in Medicine (AIUM) Official Statements

CLINICAL SAFETY
Official Statement
Approved
March 1993
October 1982

Diagnostic ultrasound has been in use since the late 1950s. Given its known benefits and
recognized efficacy for medical diagnosis, including use during human pregnancy, the American
Institute of Ultrasound in Medicine herein addresses the clinical safety of such use:

No confirmed biological effects on patients or instrument operators caused by exposure at

intensities typical of present diagnostic ultrasound instruments have ever been reported. Although the
possibility exists that such biological effects may be identified in the future, current data indicate that
the benefits to patients of the prudent use of diagnostic ultrasound outweigh the risks, if any, that may
be present.

90
MAMMALIAN IN VIVO ULTRASONIC BIOLOGICAL EFFECTS
Official Statement
Approved
October 1992
August 1976

Information from experiments utilizing laboratory mammals has contributed significantly to

our understanding of ultrasonically induced biological effects and the mechanisms that are most likely
responsible. The following statement summarizes observations relative to specific ultrasound
parameters and indices. The history and rationale for this statement are provided in Bioeffects and
Safety of Diagnostic Ultrasound (AIUM, 1993).

In the low megahertz frequency range there have been no independently confirmed adverse
biological effects in mammalian tissues exposed in vivo under experimental ultrasound conditions, as
follows.

a. When a thermal mechanism is involved, these conditions are unfocused-beam

intensities* below 100 mW/cm2, focused-beam† intensities below 1 W/cm2, or thermal index values
less than 2. Furthermore, such effects have not been reported for higher values of thermal index when it
is less than

log10t
6 - ———
0.6

where t is exposure time ranging from 1 to 250 minutes, including off-time for pulsed
exposure.

b. When a nonthermal mechanism is involved,# in tissues that contain well-defined gas

bodies, these conditions are in situ peak rarefactional pressures below approximately 0.3 MPa or
mechanical index values less than approximately 0.3. Furthermore, for other tissues no such effects
have been reported.

CONCLUSIONS REGARDING GAS BODIES

Official Statement
Approved
March 1993
October 1987

1. The temporal peak outputs of some currently available diagnostic ultrasound devices
can exceed the threshold for cavitation in vitro and can generate levels that produce extravasation of
blood cells in the lungs of laboratory animals.

2. A Mechanical Index (MI)* has been formulated to assist users in evaluating the
likelihood of cavitation-related adverse biological effects for diagnostically relevant exposures. The MI
is a better indicator than derated spatial peak, pulse average intensity (ISppA.3) or derated peak
rarefactional pressure (rr.3) for known adverse nonthermal biological effects of ultrasound.

3. Thresholds for adverse nonthermal effects depend upon tissue characteristics and
ultrasound parameters such as pressure amplitude, pulse duration and frequency. Thus far, biologically
significant, adverse, nonthermal effects have only been identified with certainty for diagnostically
relevant exposures in tissues that have well-defined populations of stabilized gas bodies. For
extravasation of blood cells in postnatal mouse lung, the threshold values of MI increase with
decreasing pulse duration in the 1-100 ms range, increase with decreasing exposure time and are
weakly dependent upon pulse repetition frequency. The threshold value of MI for extravasation of

91
blood cells in mouse lung is approximately 0.3. The implications of these observations for human
exposure are yet to be determined.

4. No extravasation of blood cells was found in mouse kidneys exposed to peak

pressures in situ corresponding to an MI of 4. Furthermore, for diagnostically relevant exposures, no
independently confirmed, biologically significant adverse nonthermal effects have been reported in
mammalian tissues that do not contain well-defined gas bodies.

CONCLUSIONS REGARDING EPIDEMIOLOGY

Official Statement
Approved
March 1995

Based on the epidemiologic evidence to date and on current knowledge of interactive

mechanisms, there is insufficient justification to warrant a conclusion that there is a causal relationship
between diagnostic ultrasound and adverse effects.

CONCLUSIONS REGARDING HEAT

Official Statement
Approved
March 1993,
October 1987

1. Excessive temperature increase can result in toxic effects in mammalian systems. The
biological effects observed depend on many factors, such as the exposure duration, the type of tissue
exposed, its cellular proliferation rate, and its potential for regeneration. Age and stage of development
are important factors when considering fetal and neonatal safety. Temperature increases of several
degrees Celsius above the normal core range can occur naturally; there have been no significant
biological effects observed resulting from such temperature increases except when they were sustained
for extended time periods.

a. For exposure durations up to 50 hours, there have been no significant biological

effects observed due to temperature increases less than or equal to 2°C above normal.

b. For temperature increases greater than 2°C above normal, there have been no
significant biological effects observed due to temperature increases less than or equal to

log 10t
6 - ———
0.6

where t is the exposure duration ranging from 1 to 250 minutes. For example, for
temperature increases of 4°C and 6°C, the corresponding limits for the exposure duration t are 16 min
and 1 min, respectively.

c. In general, adult tissues are more tolerant of temperature increases than fetal and
neonatal tissues. Therefore, higher temperatures and/or longer exposure durations would be required
for thermal damage.

2. The temperature increase during exposure of tissues to diagnostic ultrasound fields is

dependent upon (a) output characteristics of the acoustic source such as frequency, source dimensions,
scan rate, power, pulse repetition frequency, pulse duration, transducer self heating, exposure time and
wave shape and (b) tissue properties such as attenuation, absorption, speed of sound, acoustic

92
impedance, perfusion, thermal conductivity, thermal diffusivity, anatomical structure and nonlinearity
parameter.

3. For similar exposure conditions, the expected temperature increase in bone is

significantly greater than in soft tissues. For this reason, conditions where an acoustic beam impinges
on ossifying fetal bone deserve special attention due to its close proximity to other developing tissues.

4. Calculations of the maximum temperature increase resulting from ultrasound

exposure in vivo should not be assumed to be exact because of the uncertainties and approximations
associated with the thermal, acoustic and structural characteristics of the tissues involved. However,
experimental evidence shows that calculations are capable of predicting measured values within a
factor of two. Thus, it appears reasonable to use calculations to obtain safety guidelines for clinical
exposures where temperature measurements are not feasible. To provide a display of real-time
estimates of tissue temperature increases as part of a diagnostic system, simplifying approximations are
used to yield values called Thermal Indices.* Under most clinically relevant conditions, the soft-tissue
thermal index, TIS, and the bone thermal index, TIB, either overestimate or closely approximate the
best available estimate of the maximum temperature increase (DTmax). For example, if TIS = 2, then
DTmax 2°C.

5. The current FDA regulatory limit for ISPTA.3 is 720 mW/cm2. For this, and lesser
intensities, the best available estimate of the maximum temperature increase in the conceptus can
exceed 2°C.

6. The soft-tissue thermal index, TIS, and the bone thermal index, TIB, are useful for
estimating the temperature increase in vivo. For this purpose, these thermal indices are superior to any
single ultrasonic field quantity such as the derated spatial-peak, temporal-average intensity, ISPTA.3.
That is, TIS and TIB track changes in the maximum temperature increases, DTmax, thus allowing for
implementation of the ALARA principle, whereas ISPTA.3 does not. For example,

a. At a constant value of ISPTA.3, TIS increases with increasing frequency and with
increasing source diameter.
b. At a constant value of ISPTA.3, TIB increases with increasing focal beam diameter.

(Reprinted with permission of AIUM, 14750 Sweitzer Lane, Suite 100, Laurel, MD 20707-
5906)

NOTIUNI INTRODUCTIVE
Ecografia obstetricala- instrument eficace
Examenul ecografic obstetrical standard
“Ecografistii”
Scopuri- ecografie obstetricala
Continutul- ecografie obstetricala
Scopurile cursului
“Tipuri” de ecografie obstetricala
Determinarea varstei gestationale
Ecografia in T I
uter, anexe (CL)
morfologie embrio-fetala
diagnosticul sarcinii
Determinarea varstei gestationale
anomalii

93
Ecografia in T II-III
stabilirea varstei gestationale-BPC
-HC
-AC
-FL
aprecierea cresterii fetale
morfologia fetala * generalitati- momentul examenului
- examinator/ examinare
- acuratete
* cap
- sectiune transtalamica
- sectiune transventriculara
- sectiune transcerebrala
- anomalii
* coloana
* Cord
* torace
* abdomen- stomac
- ficat, splina, vezica urinara, intestin.
- perete
* aparat urinar- vezica
- rinichi
* aspect exterior, schelet
LA
Placenta
Aprecierea ..... fetale
Uter, anexe
Sarcina multipla
Ecografia interventionala
Doppler
Securitate
screening- controversat
Ecografia obstetricala- instrument eficace
Dg. de curatete al varstei gestationale
Dg. sarcinei multiple precoce
Dg. anomalii morfologice precoce
Aprecierea LA
Cresterea fetala
Bunastarea fetala
Localizarea placentei
In orice complicatie ulterioara – decizie facilitata de o ecografie precoce (Fp, HLG, cezariana
iterativa)
18-20 SA- suficient de devreme – biometrii ....
tarziu - anomalie fetala
Examenul ecografic obstetrical “standard”
( nivelul I biometrii/ nivelul II anatimie- depasit
 consult in echipa
 consult tentit
Ecografia obstetricala:
Scopuri
 evidentierea sarcinei, fatului, anexelor in II-III, diminsiuni
 recunoasterea normalului/ anormalului anatomic
 realizarea de masuratori
Continutul ex. US baza:
 apreciere fetala( nr., viabilitate, pozitie

94
  biometrii fetale, greutate(FW)
 apreciere LA
 localiz. placentei
Scopul cursului:
 familializarea cu notiunile de baza( dg. de sarcina, biometrie fetala)
 recunoasterea anatomiei fetale
 facilitarea practicii
 ajutor in decizia de cunsult in echipa/ trimitere
 ajutor pentru studiul ulterior( teoretic, practic)
ecografia:
 transvaginala Tr. I
 transabdominala- Tr. II-III
 transperineala- col uterin
Determinarea varstei gestationale:
 multitudine de parametrii
 varietate individuala
 diferite sisteme de referinta
Tr. I:
 gestational sac (GS)
 crown-rump length (CRL)
Tr. II-III:
 biparietal diameter(BPD)
 head circuference(HC)
 abdominal circumference (AC)
 femur length (FL)
acuratetea determinarii varstei gestationale bazata pe diferite biometrii
Dg. s. ( deficil FU, CO)
 sac gestational fara elemente E, nedeosebit de o colectie lichidiana ( NU dg. s.)
 din momentul sacului vetilin (6 SA)
 E 6 SA – activ. cardiaca
Morfologia E-fetala Tr. I:
 sacul gestational ( chorionic) prima structura vizibila, celum extraembrionar
 creste 1 mm/ zi
Caracteristici sac N.:
 localiz. fund uterin
 rotund
 incorpurat de o coroana hiperecogena (chorion, vilozitati)
 embrion 6 SA ( la inceput pol embrionar)
 activ. cardiaca ( trebuie sa fie vizibila in E > 5mm CRL( mod M) la E~ 1mm, SG
20mm
 progresiv- alte structuri (cap, corp)
Vezicula vetilina (yolk sac):
 la 6 SA vizibil
 in afara sacului amniotic- < 6mm
 rotund
 unic (exceptie S. multipla)
 membrana amniotica nelipita 7 SA
 8 SA vizibil clar
Varsta gestationala:-(SG )
 vizibil la 5 SA (4mm)
 masurat-mediu MSD  (lungime+inaltime+grosime)/3
2 imagini sau 3D
 varsta gestationala (zile) = MSD(mm) +304
CRL:
 E vizibil la 6SA

95
  masuratul la 7 SA
 adecvat la 7- 13 SA
 varsta gestationala (SA) = CRL+6.5
BPD:
 nivel plan transversal (axial)- talamus, cavum sptum, pellciudum,cerebel
 nivel plan transversal (cranial)- sus venriculi- (caudal) jos orbita, fosa post. (cu
emisfere cerebrale)
 conventional- leading edge(margine ext., margine int.)
 6cm= 24SA 11 zile .... viabilitate
 in 5% nevizualizate ( pozitie fetala)
 index cefalic BPD/OFD=0.780.05
HC:
 traseu
 calculata automat din 2 diam. sau manual ( BPD+OFD)+II/2(1.57)
 BPD ( biparietal diameter)
 OFD ( occiputofrontal diameter- coventional- extern – extern
 in caz de bradi/dolicocefalie
AC:
 c. m. complexa
 marker fetal variabil
 miscari respiratori fetale(locatie, forma abdomen)
 umbra- coloana, membre identificare cutanata dificila
 plan :
 normal pe axul lung al corpului
 nivel- stomac
 nivel- jonctiune v. ombilicala/ sinus portal
 HC/AC= parametru in FG
FL:
 trohantero-extremitatii distale
 excludere: epifide, alte ecouri periostale
 imagine variabila dependent de 9 varsta gestationala, ecouri epifizare)
 sonde sectoriale-  daca departe, lateral
 preferabil axial> lateral
Aprecierea cresterii fetale:
 avantajul unei determinari precoce a varstei gestationale
 masuratori multiple in timp per parametru inscrierea pe un grafic BPD, FL, HC, AC,
HC/AC=Fetal weight)
 combinatii, formule
 simetrica/ asimetrica
 reevaluare la 2 SA
 macrosomie (1.4cm+ abd 87%>4000g.
 unul din aspectele c. m. incarcate de responsabilitate
 2-3 % anomalii congenitale majore neidentificate
 responsabilitate justificata a N. congenitale  implicatii majore asupra momentului,
caii, locului nasterii si medicolegal
SNC:
Anomalii observate intotdeauna:
 anencefalie
 hidrocefalie
 ventriculomegalie>15mm
 chiste de fosa posterioara
 holoprosencefalie alobar
Anomalii de obicei neobservate:
 spina bifida
 agenezie parietala de corp calos

96
  chiste mici paraencefalice
 hemivetebre
 scolioza fixata
Corp:
Anomalii observate:
 perete, membre
 obstructie intestinala proximala
 hidrotorax cu deplasare mediastinala
 ascita importanta
 omfalocefal continand ficatul sau intestin
 agenezie renala bilaterala
Anomalii de obicei neobservate:
 majoritatea anomaliilor craniofaciale
 intersexualitatea
 agenezie renala unilaterala
 gastroschizis<1cm
 ciste abdominale sau tumori toracice
 hernia diafragmatica cu stomacul in abdomen
 majoritatea anomaliilor de schelet
Momentul examenului:
 normalul mimeaza anormalului (hrnierea fiziologica a pretelui abdominal ant. 
omfalocel)
 anormalul mimeaza normalului(anencefalia)
 daca stomac, rinichi, splina, creier, craniu, coloana, membre, perete abdominal
anterior) intre 9-14 SA
Acuratete:
 sensibilitate totala 53%
 specialitate totala 99%
Examenator/ examinare: rolul examinatorului
 interpretatrea fiziopatologica, risc implicat.
 examen detaliat:
 34 sectiuni + masuratori specifice
 pentru fiecare str. normala, suspec., anormal, slab viz., inaplicabila
 1 h- daca este anormal
Morfologie fetala:
Sectiune transtalamica
8. Cap:
 imposibilitate masurare- anencefalie
 forma – 0.71<BPD?OFD<0.87
 Bradicefalic > 0.87
 Dolicocefaic<0.7
 forma de “lamaie” – anomalii
 ventriculi cerebrali:
 < 20 SA pliuri de plexurile coroide( hiperecogene)
 > 20 SA ( plexurile coroide  ) – zone anecogene
 diminsiuni - sfarsitul T I- 90% din sp. i. cranial
 26-40 SA ~ 33%
 separati de o suprafata, hiperecogena = falx cerebri
 Hidrocefalie + craniu, forma rotunda
Sectiune traventriculara
Sectiune transcerebrala
 fosa posterioara
 emisfere cerebeloase- hiperecogene, rotunde
 cisterna magna- anecogena
 anormal- cerebel aplatizat, alungit semnul bauanci

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anormal:
 anencefalie
 microcefalie
 meningocefal, encefalocel
 chist plixuri coroide
 fosa post. -  cisterna magna
 hidrocefalie- ventricullateral> 10mm
 colpocefalie
 holo[rosencefalie
 parencefalie
 agenezie corp calos
 t. i. craniene
 hidroanencefalie
 poencefalie
 anevrisme(v. Galen)
9. coloana:
 planuri:
 sagitale:
 linie cutanata intacta
 lamele post.
 corpii vertebrali
pe intreaga lungime- baza craniului- extremit. caudala
 cronar:
 lamele post. paralele
 transversal:
 piela intacta
 lamele post.
 corp vertebral
anormal spina bifide, meningocel, mielomeningocel
3. Cord:
 examen pretentios
 necesita timp ecipament corespunzator experienta
 standard –imaginea tetracamerala
Confirma date anatomice majore
-inima este in parte stanga a toracelui
-deasupra diafragmului. (Nu exista structuri anormale in torace-stomac).
-1/3 din  toracelui
-2 ventriculi prezenti aproximativi egali
- sept interventricular prezent
-2 atrii, aprox. egali
- valvele atrioventriculare- septul se intersecteaza in mijlocul inimii
- nu exista lichid percardiac
- nu exista lichid pleural
Examen detaliat cardiac fetal:
 imagine tetracamerala
 orice anormal fetal
 antecedente fam. b. cardiaca
 fact. de risc matern:
 DZ in momentul conceptiei
 b. de colagen
 varsta inaintata
 expunere la droguri teratogene ( dilatin, alcool, isotretinoin)
 inf. virala (rubeola) in sarcina
 IUGR
 anomalii cromosomiale cunoscute

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  aritmie fetala
 hidrops nonimun
Defecte observate:
 ectopia cardiaca
 ventricul hipoplazic(unic)
 lichid in pericord(hidrops)
 cardiomegalie, hipertrofie ( cardiomiopatie)
 defecte septale interatriale si interventriculare mari
 tumori cardiace
 atrezia valvulara atrioventriculara
sectiune parasagitala- prin VL, A< o parte VD, AS,
ax scurt- Valve A, P, ram D-AP
marile vase- vena cava, A, P (dupa incrucisare)
O sectiune sagitala cu cord, stomac, vezica- elimina numeroase anomalii.

1. prezentare generală
2. anatomie normală
3. ecografia în patologia pelvină
4. ecografia sânului

scopul examenului ecografic ginecologic:

 diagnosticul, localizarea / caracterizarea formaţiunilor pelvine
 diagnosticul, localizarea precisă a sarcinii
 evaluarea conţinutului uterin
 aprecierea zonelor dificil de examinat
 evaluarea lichidului intraperitoneal
 flux sanguin pelvin
 evidenţierea fiziologiei:
 identificarea normalului (+ diagnostic diferenţial)
 monitorizarea foliculilor
 aspect, grosime endometrială

obiectivele cursului:
 prezentarea imaginilor normale
 evidenţierea normalului prin contrastul cu imaginile anormale
 diagnostic diferenţial cu alte organe, formaţiuni abdominale pelvine
 discuţia situaţiilor frecvent întălnite
 ajutor pt. - practica asistată / individuală
- solicitarea / realizarea unui consult ecografic detaliat ginecologic

tehnica standard de examinare

 acoperire în totalitate
 documentaţie
 secţiuni – longitudinală
- transversală
- oblice
- coronară (vaginală)
- vezică în semirepleţie pt. ecografie abdominală

tipuri de ecografie: - abdominală

- transvaginală:
 secţiune coronară
 vezică în depleţie
 rezoluţie > (apropiere, frecvenţă, îndepărtarea formaţiunilor interferente)
 caracterizarea superioară a uterului, ovarelor, tumorilor pelvine
 interferează bine cu examinarea ginecologică

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 - transperineală
- cu substanţă de contrast

necesar pentru ecografia ginecologică

1. cunoştinţe aprofundate de fiziologie / fiziopatologie
2. posibilitatea + anamneză, examen ginecologic
3. experienţă ecografică
4. aparat

II. anatomie normală

1. uter
2. vezică urinară
3. uretra, joncţiunea uretro-vezicală
4. vagin
5. anexă – ovar
- trompă
6. alte imagini pelvine

6. uter – reper ecografic

- în plan median pelvic
- ecogenitate diferită de restul organelor
- endometru – ecogenitatea variabilă (apă, densitate celulară)
pe parcursul ciclului (>preovulator, luteal)
sarcină – decidualizare
menopauză <3 – 5 mm
grosime - > sub stimul E (1-5 mm)
SoHSG, HyCoSy – principiu
- poziţie faţă de axul – cervical
vaginal
- col

7. vezică urinară – reper ecografic

! umplere exagerată
! artefact: near field reverberation
lateral: m. iliopsoas (nu tumori)
8. uretră – eco vaginal, perineal
9. vagin – structură tubulară
cavitate virtuală
caudal de vezică / col
10. ovar – poziţie variabilă – lungime ligament lombo-ovarian
aderenţe
alte variante / anomalii anatomice
lateral de uter
mobilă (eco vaginal, fără aderenţa)
utilă identificarea vaselor iliace
dezvoltare foliculară
Doppler - > flux diastolic în faza postovulatorie / luteală
trompe – normale – dificil de vizualizat
- HyCoSy
11. alte imagini pelvine
- ligamente - nu / rar, ligamente rotunde
- intesrtine - heterogenitate (gaze, conţinut)
peristaltism
- uretere - rar dacă nu special căutate
- secţiune transversală lângă marginea colului

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 - vascularizaţie - vase iliace
- a. uterine – ocazional P1 > în S. precoce
- Doppler – a. ovariene / uterine
- lichid FDS Douglas - puţin – menstruaţie, ovulaţie

III. ecografia în patologia pelvină

A. noţiuni generale – tumorile abdominopelvine
caracterizarea tumorilor
posibilităţi
protocolul analizelor ecografice
diagnosticul diferenţial
B. patologia organelor genitale – uter
ovare
trompe
alte organe, imagini asociate

tumorile abdominopelvine:
 piatră de încercare pt. examinator (diagnostic diferenţial)
 nu există o ierarhizare a metodelor de investigaţie
 nu trebuie inversată ordinea normală la examinare
 indicaţii de conduită – observaţie / supraveghere
completare imagistică, investigaţii
terapie
 abilitate de – detecţie
recunoaştere
apreciere
decizie

caracterizare:
 localizare (toate, + meta)
 dimensiuni (detecţie cât mai precoce)
 extindere
 caracter benign / malign
 iatrogenitate
 posibilităţi de ameliorare a imaginii:
- focalizarea fascicolului ( > rezoluţiei în adâncime)
- armonice superioare
- SoHSG, HyCoSy
- Doppler
- 3D
- ecografie intervenţională

protocolul analizei ecografice:

1. localizare, origine
2. relaţii anatomice cu alte structuri
3. dimensiuni
4. extindere
5. contur
6. grosime perete
7. conţinut – lichid - anecogene / hipoecogene
bună transmisie US
margine suprafaţă distală strălucitoare (accentuare distală)
- solid - > ecogenitate
atenuarea transmisiei us
margine – proximală distală

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 distală neclară
- complex
- septuri
8. semne asociate (meta, ascită)

diagnosticul diferenţial al tumorilor pelvine după conţinut

B.patologia organelor genitale

uter – poziţie
miometru
endometru, cavitate uterină
col
anomalii congenitale

poziţie – deviat de formaţiuni tumorale

- fixat de proces aderenţial
miometru – leiomiom - subseros / intramural / submucos
unic / multiplu
hiperecogen
contur uterin neregulat
semne de degenerare (+ calcificare)
! importanţă – terapeutică
- supraveghere
- sarcom – ecogenitate complexă, asemănătoare miomului degenerat
> flux diastolic (Doppler)
endometru
- polipi (+ SoHSG, HyCoSy), hipertrofie / plazie
- urmărire, tratament cu Tamoxifen
- carcinom +_: - cavitate neregulată
interes – invazie miometrială

cavitate uterină:
 lichid – sânge, sarcină
suspiciune infecţii, neoplasm (ovarian, tubar, endometrial, cervical)
 conţinut mixt
sânge
sarcină – normală
implantaţie cornuală, istmică (!ruptură uterină catastrofică)
avort – ecouri neorganizate
SG neregulat
hemoragie intradeciduală
S. anembrionică (ou clar)
molă
 DIU – localizare
ghidaj pt. extracţie (migrat + s. iu)

col: - volum cancer cervical

invazie parametrială (!TR) endorectală
Doppler a. uterină
S. cervicală (diagnostic diferenţial avort incomplet)

anomalii congenitale
 imperforaţie himenală, sept vaginal transversal
 hematocolpos, hematometrie (+ ex. transperineal)
 agenezie mulleriană Mayer – Rokitansky – Kustner – Hauser

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  variate anomalii – bicorn, dublu, septat (complet, incomplet) dianostic dificil: septat / dublu (!
anomalii renale asociate)
 sindromul rezistenţei la E; nu există uter, ovare / există testicole
 disgenezii ovariene 45x -> uter hipoplazic
monitorizare E , tratament

ovare:
 procese funcţionale
 tumori
 anomalii congenitale (agenezie, anomalii genetice)

procese funcţionale:
1. folicul
monitorizare foliculară HSO
prelevare ovocitară
2. PCO – imagini variabile
+ hipertecoză - < nr. foliculi
ecogenitate
monitorizarea tratamentului
tumori:
 varietate mare
 clasificarea complexă
 limită benign / malign
 exemple
 diagnostic diferenţial – anse intestinale, cec secţiune transversală
varicozităţi pelviene
rinichi ectopic
abcese, tumori apendiculare

diferenţiere tumori benigne/ maligne ovariene

contur neted, regulat neregulat, vegetaţii
pereţi subţiri groşi
conţinut omogen complex, septuri, vegetaţii, mase
solide
vacularizaţie R1<o.4, P1<0.8 (> flux
diastolic)
tumoră – vase neregulate
semne asociate ascită, metastaze

chist complexe solide

limite interne netede 1 1 -
neregulate 2 2 -
vegetaţii suspicionate 2 0 -
clare 3 2 -
septuri <3mm 0 1 -
>3mm 2 2 -
ecogenitatea părţii omogenă - 1 2
solide
neomogenă - 2 4
lichid în faza 0 0 0
intraperitoneal preovulatorie
prezent 1 1 1

Scor <4– tumoră benignă

>4 – sispiciune malignitate

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Vascularizaţie – în sept, vegetaţii, în partea solidă, vase neregulate
!R1<0.4
P1<0.8

folicul matur – chist unilocular

 = 20 –25 mm
conţinut anecogen
perete subţire, perfect regulat
corp galben – formaţiune chistică uniloculară, anecogenă / mixtă, uneori cu septuri fine
 = 15 – 30 mm
corp folicular – unilocular
anecogen
 = 50– 100mm
perete subţire, regulat
întărire acustică posterioară

corp galben de sarcină – cu septuri fine

perete subţire
conţinut mixt cu zone solide şi lichidiene care nu respectă regulile gravitaţiei

chist seros de indiviziune – unilocular ! semnificaţie deosebită în menopauză

anecogen >3,5 – 5 cm, persistent
perete subţire

chist endometrial – unic / multiplu

conţinut cu multiple ecouri de amplitudine scăzută
 = 30-100mm
perete gros ?

chist dermoid – conţinut complex (predominant solid, componente ecogenice, nivel fluid / solid, uretră
posterioară)
chisat unilocular, în contact cu peretele unuia sau mai multor noduli cu aspect
ecogenic (patognomonic, rar, nodulul Rokitansky )
chist septat
solid

chistadenom seros – chist unilocular / uneori vegetaţii

conţinut anecogen
întărire acustică posterioară
dimensiuni variabile
uneori septate, multiloculare, multiple

chistadenocarcinom seros – conţinut complex, arii solide

vegetaţii intrachistice
septuri groase, neregulate
ascită (! Sdr. Demon – Meygs)
screening
detecţie tumorală reziduală

chistadenom mucinos – septat

ecouri fine, diseminate

chistadenocarcinom mucinos – conţinut complex

arii solide, vegetaţii

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carcinom endometrioid – tumoră chistică
vegetaţii multiple
tumoră solidă
bilaterală 50%

trompe – BIP
endometrioză
SE
carcinom
anomalii congenitale

BIP – hidrosalpinx
piosalpinx
abces tubo-ovarian
imagini complexe (+ aderenţe, implicare ovariană)

endometrioză – imagini complexe – greu de diferenţiat de BIP

SE – cavitate uterină virtuală > 1500 mUI/ml (3000 mUI/ml pentru elimina s. multiplă)
formaţiune anexială – complexă
rar SG
foarte rar E, activitate cardiacă
lichid în Douglas (foarte rar S. heterotipică)

carcinom – imagini complexe

anomalii congenitale – hidatide (Morgagni)

alte organe pelvine, imagini asociate

A. peritoneu – BIP - > ecogenitate, aderenţe
B. lichid în Douglas – sânge
puroi
ascită
C. intestine – distensie – diagnostic diferenţial cu tumoră chistică / mixtă anexială
D. uretere – dilatate
E. vascularizaţie – neovascularizaţie
flux diastolic
F. adenopatii

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