The Uses and Limitations of the F e t a l Bi o p h y s i c a l P ro f i l e

Yinka Oyelese,
KEYWORDS  Fetal biophysical profile  Antepartum fetal assessment  Real-time ultrasound  Non-stress test
MD, MRCOG
a,b,

*, Anthony M. Vintzileos,

MD

c,d

In the second half of the twentieth century, true antepartum fetal assessment became possible, mainly due to the advent of real-time ultrasound. Initially, the most widely used form of antepartum fetal assessment was electronic fetal heart rate (FHR) monitoring, through the nonstress test (NST) or the oxytocin-induced contraction stress test (CST). It was soon realized, however, that these forms of monitoring had significant limitations. The NST or CST, when normal, is highly predictive of fetal well-being. Both the NST and CST, however, have high false-positive rates (45% 75%),1,2 with the possibility of unnecessary and sometimes preterm delivery of a fetus actually in good health. The biophysical profile (BPP) allows a more thorough evaluation of fetal well-being and has the potential to significantly reduce the false-positive rate of the NST/CST. The BPP was initially described by Manning and colleagues3 in 1980 and aimed at a more complete evaluation of fetal well-being. The fetal BPP, as these investigators described it, consisted of 5 fetal activities: FHR assessment, fetal movement (FM), fetal tone (FT), fetal respiratory movements, and amniotic fluid (AF) volume (Table 1). Each of these components, when present (normal), is assigned a score of 2.

The Perinatal Institute, Department of Obstetrics & Gynecology, Jersey Shore University Medical Center, Suite 203, 1944 State Route 33, Neptune, NJ 07753, USA b Division of Maternal Fetal Medicine, Department of Obstetrics, Gynecology & Reproductive Sciences, UMDNJ-Robert Wood Johnson Medical School, 125 Paterson Street, New Brunswick, NJ 08901, USA c Department of Obstetrics & Gynecology, Winthrop University Hospital, 259 First Street, Mineola, NY 1150, USA d Department of Obstetrics, Gynecology & Reproductive Medicine, State University of New York, Stony Brook, NY 11794, USA * Corresponding author. Division of Maternal Fetal Medicine, Department of Obstetrics, Gynecology & Reproductive Sciences, UMDNJ-Robert Wood Johnson Medical School, 125 Paterson Street, New Brunswick, NJ 08901. E-mail address: Yinkamd@aol.com Clin Perinatol 38 (2011) 4764 doi:10.1016/j.clp.2010.12.008 perinatology.theclinics.com 0095-5108/11/$ see front matter 2011 Elsevier Inc. All rights reserved.

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Table 1 Fetal biophysical profile scoring Score 2 Movements Three or more gross body movements in a 30-minute period. Simultaneous trunk and limb movements count as a single movement At least one movement of a limb from a position of flexion to one of extension, with a rapid return to flexion At least 30 seconds of sustained FBMs observed over a 30-minute period At least a single amniotic fluid pocket measuring 2 cm 2 cm in 2 perpendicular planes At least 2 accelerations (of >15 bpm, lasting at least 15 seconds) in a 40-minute period Score 0 Fewer than 3 gross body movements in a 30-minute period

Tone

Fetal limb in extension with no return to flexion with movement

Breathing

Fewer than 30 seconds of sustained FBMs observed over a 30-minute period No amniotic fluid pocket that measures at least 2 cm 2 cm in 2 perpendicular planes Fewer than 2 accelerations in 40 minutes

AF

FHR

Data from Manning FA, Platt LD, Sipos L. Antepartum fetal evaluation: development of a fetal biophysical profile. Am J Obstet Gynecol 1980;136:78795.

Thus, the maximum score attainable is a 10. Because of their belief that fetuses that showed some biophysical activities that did not meet the criteria for a score of 2 are likely different from those that show a total absence of the particular biophysical activity (both assigned a score of 0 according to Mannings BPP), Vintzileos and colleagues4 subsequently proposed an alternative BPP scoring system (Box 1). In this scoring system, intermediate scores of 1 were given when a fetus demonstrated some activity that did not qualify for a score of 2 in an attempt to determine for each component the minimum requirements for normalcy. In addition, these investigators added a sixth component of the BPP scoring system, placental grading (PL). In this scoring system, the maximum score possible is 12.
OBJECTIVES OF THE BIOPHYSICAL PROFILE

The primary objectives of the BPP are to reduce stillbirth and to detect hypoxia early enough to allow delivery in time to avoid permanent fetal damage resulting from fetal asphyxia. Before going into a discussion about the BPP, however, it is important to understand that the efficacy of any fetal surveillance method to prevent fetal death or damage depends on an understanding of the particular pathophysiologic process that leads to neurologic damage or fetal death.5,6 Kontopoulos and Vintzileos5 have previously described the different pathophysiologic processes that result in fetal death and asphyxia (Table 2) and proposed the concept of condition-specific antepartum fetal testing, with testing modalities selected based on the particular process that places a fetus at risk. It is crucial for obstetricians to realize that there is no ideal test for every high-risk fetus/pregnancy.6 Some common clinical indications for antepartum fetal surveillance are shown in Box 2. Before deciding about the appropriate antepartum testing, however, clinicians should always take into consideration the specific pathophysiologic process or processes that accompany these clinical indications.

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Box 1 Criteria for scoring biophysical variables according to Vintzileos and coworkers Nonstress test Score 2 (NST 2): 5 or more FHR accelerations of at least 15 beats per minutes (bpm) in amplitude and at least 15-second duration associated with FMs in a 20-minute period. Score 1 (NST 1): 2 to 4 accelerations of at least 15 bpm in amplitude and at least 15-second duration associated with FMs in a 20-minute period. Score 0 (NST 0): 1 or less acceleration in a 20-minute period. Fetal movements Score 2 (FM 2): at least 3 gross (trunk and limbs) episodes of FMs within 30 minutes. Simultaneous limb and trunk movements were counted as a single movement. Score 1 (FM 1): 1 or 2 FMs within 30 minutes. Score 0 (FM 0): absence of FMs within 30 minutes. Fetal breathing movements (FBMs) Score 2 (FBM 2): at least 1 episode of fetal breathing of at least 60-second duration within a 30-minute observation period. Score 1 (FBM 1): at least 1 episode of fetal breathing lasting 30 to 60 seconds within 30 minutes. Score 0 (FBM 0): absence of fetal breathing or breathing lasting less than 30 seconds within 30 minutes. Fetal tone Score 2 (FT 2): at least 1 episode of extension of extremities with return to position of flexion and also 1 episode of extension of spine with return to position of flexion. Score 1 (FT 1): at least 1 episode of extension of extremities with return to position of flexion or 1 episode of extension of spine with return to flexion. Score 0 (FT 0): extremities in extension. FMs not followed by return to flexion. Open hand. Amniotic fluid volume Score 2 (AF 2): fluid evident throughout the uterine cavity. A pocket that measures greater than 2 cm in vertical diameter. Score 1 (AF 1): a pocket that measures less than 2 cm but more than vertical diameter. Score 0 (AF 0): crowding of fetal small parts. Largest pocket less than 1 cm in vertical diameter. Placental grading Score 2 (PL 2): placental grading 0, 1, or 2. Score 1 (PL 1): placenta posterior difficult to evaluate. Score 0 (PL 0): placental grading 3. Maximal score, 12; minimal score, 0. From Manning FA, Platt LD, Sipos L. Antepartum fetal evaluation: development of a fetal biophysical profile. Am J Obstet Gynecol 1980;136(6)78795; Copyright Elsevier, used with permission.

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Table 2 Antepartum maternal/fetal pathophysiologic processes that place the fetus at risk of in utero death or neurologic damage Pathophysiologic Process Decreased uteroplacental blood flow Maternal/Fetal Condition Chronic hypertension Preeclampsia Collagen/renal/vascular disease Most cases of fetal growth restriction (ie, <3234 wk) Postdates pregnancy, some fetal growth restricted cases (ie, >3234 wk) Fetal hyperglycemia Fetal hyperinsulinemia PROM Intra-amniotic infection Maternal fever, primary subclinical intra-amniotic infection Fetomaternal hemorrhage Erythroblastosis fetalis Parvovirus B19 infection Cardiac arrhythmia Nonimmune hydrops Placental chorioangioma Aneurysm of the vein of Galen Umbilical cord entanglement (monoamniotic twins) Velamentous cord insertion/funic presentation Noncoiled umbilical cord Oligohydramnios

Decreased gas exchange Metabolic aberrations Fetal sepsis

Fetal anemia

Fetal heart failure

Umbilical cord accident

Box 2 Some common clinical indications for antepartum fetal surveillance 1. Intrauterine growth restriction 2. Prior stillbirth 3. Diabetes 4. Hypertension 5. Preeclampsia 6. Postdates pregnancies 7. Preterm premature rupture of the membranes (PPROM) 8. Oligohydramnios 9. Decreased FMs 10. Prior stillbirth 11. Maternal lupus 12. Multifetal pregnancies, in particular those with growth disturbances or discordance 13. Cholestasis of pregnancy

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TECHNIQUE

Two methods are used in the performance of the BPP. The first is the performance of an NST. This is a continuous FHR tracing. The normal fetal baseline heart rate is 110 to 160 bpm. The NST is considered reactive when there are 2 or more accelerations (a short increase in FHR of >15 bpm, lasting at least 15 seconds) in 20 minutes. For gestations less than 32 weeks, the qualifying criteria for accelerations are greater than 10 bpm, lasting at least 10 seconds. A reactive NST is assigned 2 points in the BPP. Real-time ultrasound is then performed. In this examination, fetal gross body movements, tone, respiratory movements, and AF volume are assessed. A score of 2 points is assigned for each of these biophysical activities that is present. It is crucial that proper technique be employed when performing a BPP. To obtain 2 points for each biophysical activity, the following should be present: 1. For FMs, there should be at least 3 rolling movements of the fetal trunk in 30 minutes. Isolated limb movements do not qualify. 2. There should be continuous FBMs present for at least 30 seconds, with breathbreath intervals of less than 6 seconds. 3. To qualify for FT, there must be a rapid change from flexion to extension and then back to flexion. 4. The AF volume measurement should be performed with the transducer perpendicular to the floor, and measurements should only include cord-free pockets. The ultrasound portion of BPP is considered complete when all the biophysical activities have been observed, yielding a score of 8/8 (Manning scoring system) or 12/12 (Vintzileos scoring system), or after 30 minutes of scanning. The BPP is completed in the first 4 minutes 90% of the time and the mean time taken to complete the BPP is under 8 minutes.7 Vibroacoustic stimulation using an artificial larynx may shorten the time of testing as well as the number of nonreassuring tests.8,9
RATIONALE FOR THE BIOPHYSICAL PROFILE

The fetal BPP is based on the principle that the fetal biophysical activities are controlled by centers in the fetal brain that are sensitive to varying degrees of hypoxia. The presence of a particular biophysical activity is taken as evidence that the center responsible for that activity is intact and has not been subjected to hypoxia and acidosis. The absence of a particular biophysical activity does not necessarily mean that the center is malfunctioning because of fetal compromise, however. The biophysical activities are subject to periodicity; the fetus undergoes sleep cycles, and the absence of a biophysical activity may simply indicate that the testing was performed during a sleep cycle. Furthermore, maternal depressant medications may also lead to suppression of biophysical activities. The timing of the appearance of the biophysical activities has been studied.10 The first of the biophysical activities to appear is FT, controlled by a center in the fetal cortexsubcortex, which appears at approximately 8 weeks of gestation. Shortly thereafter, the FM center in the fetal cortical nuclei becomes active at approximately 9 weeks. Fetal respiratory movements, controlled by a center in the ventral surface of the fourth ventricle, are first noted at approximately 21 weeks, and FHR reactivity, regulated in the posterior hypothalamus and medulla, becomes established late in the second trimester or in the early third trimester. The proportion of NSTs that are reactive increases with gestational age up to 40 weeks.10,11 As pregnancies go past 40 weeks,

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however, FBMs and AF volume become decreased.10 Baskett11 studied 5582 women with normal pregnancy outcomes who had a total of 11,012 BPPs performed. They found that NSTs and breathing movements were more likely to be abnormal at 26 to 33 weeks of gestation when compared with later gestational ages. They also found increased rates of abnormal NSTs and AF volumes as pregnancies went past 42 weeks of gestation.11 Grade 3 placentas start to be seen at 32 weeks.10 The fetal BPP has been likened to examination of an adults vital signs and to the Apgar score in a newborn. Thus, FHR, body movements, tone, and respiratory movements assess the well-being of a fetus. FHR reactivity, movement, tone, and respiratory movements are acute markers of fetal well-being whereas AF volume and PL are chronic markers. The observation has been made that the last biophysical activities to appear in fetal life are the first to disappear when a fetus becomes compromised by acidemia or infection. This gradual hypoxia concept was first described by Vintzileos and coworkers.12 The most sensitive centers to fetal hypoxia are the FHR reactivity and breathing centers. These control the biophysical activities that appear last in gestation; they are also the first to become affected when a fetus is exposed to acidemia or infection. The authors previously showed that FHR reactivity and fetal breathing are abolished when fetal pH is less than 7.20, whereas FM and tone are abolished at pH values less than 7.10.12 As a fetus becomes progressively more hypoxic and acidemic, FMs and then tone disappear.12 The absence of FT, the fetal biophysical activity that is that last to disappear when there is fetal compromise, is associated with a higher perinatal death rate (42.8%) than the absence of any other biophysical activities.4
THE BIOPHYSICAL SCORE IS INVERSELY RELATED TO FETAL ACIDOSIS

Vintzileos and colleagues12 carried out a prospective study on 124 consecutive pregnant women undergoing cesarean deliveries prior to the onset of labor between 26 and 43 weeks of gestation. These investigators performed BPPs on these patients within 6 hours of their cesarean deliveries. They then measured the umbilical cord pH (arterial and venous) immediately after delivery (Fig. 1). They divided the women into 3 groups based on their BPP scores ( 4, 57, !8). They defined as fetal acidemia an umbilical arterial cord pH less than 7.20. They reported sensitivity, specificity, and

Fig. 1. Relationship between the fetal biophysical score and umbilical cord arterial pH. (From Vintzileos AM, Gaffney SE, Salinger LM, et al. The relationship between the fetal biophysical profile and cord pH in patients undergoing cesarean section before the onset of labor. Obstet Gynecol 1987;70:196; with permission.)

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positive and negative predictive values of an abnormal BPP score (defined as a score of <8) for fetal acidemia as 90%, 96%, 82%, and 98%, respectively.12 The 3 groups had statistically different cord arterial pH values, and the pH after delivery correlated with the BPP. All 9 fetuses with BPP scores less than 4 were acidemic. The mean umbilical arterial pH value in this group was 6.99 0.10 (mean SD). The mean umbilical artery pH in those 102 fetuses with a BPP score of greater than or equal to 8 was 7.28 0.04 (mean SD). Two fetuses with a BPP score of greater than or equal to 8 were acidemic. Nine out of 13 fetuses with a score of 5 to 7 were acidemic (mean cord pH 7.19 0.06 [mean SD]). The relationship between the biophysical score and cord venous pH was similar. Thus, this study demonstrated worsening fetal acid-base status in association with lower BPP scores. Ribbert and coworkers13 performed BPPs prior to fetal blood sampling by cordocentesis in 14 severely growth restricted fetuses and reported that fetal BPP correlated with fetal blood PO2, pH, oxygen saturation, and oxygen content. These investigators found that FHR reactivity was compromised when the observed pH subtracted from the appropriate mean for gestation ( pH) fell below 2 SDs. When the pH values fell below 3 SDs, FBMs were compromised. Fetal body movements and tone were compromised when the pH values fell below 4 SDs. Because cordocentesis allows accurate assessment of fetal blood acid-base status without confounding by labor or medications, these findings confirm that fetal BPP predicts the degree of fetal acidemia. The findings support the gradual hypoxia concept. FHR reactivity and FBMs are the first biophysical activities to become compromised in response to hypoxia/acidemia, and as hypoxia and acidemia worsen, fetal gross body movements and tone become compromised.
INDIVIDUAL FETAL BIOPHYSICAL ACTIVITIES HAVE DIFFERENT SENSITIVITIES TO FETAL HYPOXIA/ACIDEMIA

In a subsequent study, Vintzileos and colleagues14 prospectively studied 62 women undergoing cesarean delivery prior to the onset of labor, performing BPPs within 3 hours of their cesarean deliveries. They correlated the presence and absence of individual fetal biophysical activities with the umbilical cord arterial and venous pH values obtained immediately after delivery. Fetuses with absent breathing or nonreactive NSTs had lower umbilical arterial pH values than those where breathing was present or where the NST was reactive.14 Similarly, fetuses with absent movements and tone had lower umbilical arterial pH values than those in whom movement or tone were present. Closer analysis revealed that the presence of individual biophysical activities was related to the degree of fetal acidemia.14 The NST became nonreactive and FBMs became absent at higher pH values than it took for FM and tone to disappear (Fig. 2A).14 A similar pattern was observed for all other blood gases (see Fig. 2BD).14 In a study of 124 nonlaboring patients who had BPPs prior to cesarean delivery, in the 96 patients with reactive NSTs and/or fetal breathing, no fetus was acidemic.12 Fetuses demonstrating a nonreactive NST and absent breathing but with normal movements and tone had a mean umbilical arterial pH of 7.20. Fiftynine percent of fetuses in this group were acidemic. In fetuses with absent fetal breathing or nonreactive NSTs, and also with reduced FMs (1 or 2 instead of at least 3 gross body movements in 30 minutes) or tone, the mean umbilical arterial pH was 7.16. When all biophysical activities were absent, the mean umbilical arterial pH was 6.95 and all the fetuses were acidemic at birth. Of the individual biophysical components, FHR reactivity and fetal breathing had 100% sensitivities

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Fig. 2. (A) Relationship between cord artery pH and absent fetal biophysical activities. The pH tends to be lower in the absence of movements and/or tone compared with nonreactive NST or absent fetal breathing. Results are expressed in means (95% error bars). (B) Relationship between cord artery PO2 and absent fetal biophysical activities. The PO2 tends to be lower in the absence of movements and/or tone compared with nonreactive NST or absent fetal breathing. Results are means expressed in millimeters of mercury (95% error bars). (C) Relationship between cord artery PCO2 and absent fetal biophysical activities. The PCO2 tends to be higher in the absence of movements or tone compared with nonreactive NST or absent fetal breathing. Results are means expressed in millimeters of mercury (95% error bars). (D) Relationship between cord artery base excess and absent fetal biophysical activities. The base excess tends to be lower in the absence of movements or tone compared with nonreactive NST and absent fetal breathing. Results are means expressed in millimoles per liter (95% error bars). NO-FBM, absent FBMs; NO-FM, absent FMs; NO-FT, absent FT; NR-NST, nonreactive NST. (From Vintzileos AM, Fleming AD, Scorza WE, et al. Relationship between fetal biophysical activities and umbilical cord gases. Am J Obstet Gynecol 1991;165:707; with permission.)

and negative predictive values, an observation that suggests that either test is a reasonable choice for ruling out fetal acidemia at the time of testing. The combination of nonreactive NST and absent FBMs (as the abnormal test) improved the specificity and positive predictive values to 92% and 71%, respectively. Absent FT had the highest positive predictive value (100%) for fetal acidemia but low sensitivity (45%), an observation that suggests that FT alone is not a good screening test for fetal acidemia. The efficacy of the individual biophysical activities in predicting fetal acidemia is shown in Table 3.
THE SIGNIFICANCE OF OLIGOHYDRAMNIOS

Oligohydramnios is frequently considered a sign of compromised fetal well-being. Oligohydramnios may be associated with impaired uteroplacental blood flow, especially when it is in association with growth restriction. Regardless of the etiology, fetuses in pregnancies complicated by oligohydramnios are at increased risk of adverse perinatal outcomes. The reduced AF volume increases the risk of cord accidents. In a study of 7582 referred patients with high-risk pregnancies with structurally normal fetuses, Chamberlain and colleagues15 found that perinatal mortality rates were 1.97 in 1000 in the presence of normal qualitative AF volume (largest pocket >2 cm

Table 3 Efficacy of the fetal biophysical variables to predict fetal acidemia Definition of the Biophysical Variable(s) Abnormal Test Biophysical score NST, FBMs NST FBMs FMs FT AF AF PL (n, number of fetuses) <7 Nonreactive NST and no breathing Less than 1 acceleration in 20 minutes <30 Seconds Fewer than 3 Compromised or absent <1 cm <2 cm Grade 3 Sensitivity (%) (n) 90% (18/20) 100% (20/20) 100% (20/20) 100% (20/20) 50% (10/20) 45% (9/20) 35% (7/20) 45% (9/20) 5% (1/20) Specificity (%) (n) 96% (100/104) 92% (96/104) 76% (79/104) 64% (67/104) 96% (100/104) 100% (104/104) 93% (97/104) 86% (89/104) 94% (98/104) Positive Predictive Value (%) (n) 82% (18/22) 71% (20/28) 44% (20/45) 35% (20/57) 71% (10/14) 100% (9/9) 50% (7/14) 38% (9/24) 14% (1/7) Negative Predictive Value (%) (n) 98% (100/102) 100% (96/96) 100% (79/79) 100% (67/67) 91% (100/110) 90% (104/115) 88% (97/100) 89% (89/100) 84% (98/117)

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and <8 cm) compared with 37.7 in 1000 and 109.4 in 1000, respectively, in fetuses with marginal (largest pocket 12 cm) and decreased AF (largest pocket <1 cm). In a study of 6423 pregnancies greater than 34 weeks, Casey and colleagues16 found that 147 pregnancies (2.3%) were complicated by oligohydramnios.16 They found that these pregnancies had an increased risk of labor induction, nonreassuring FHR patterns, cesarean delivery, neonatal intensive care unit admission, meconium aspiration, stillbirth, and neonatal death.
PLACENTAL GRADING

PL as a component of the BPP has not found widespread acceptance. Vintzileos and colleagues4 found an increased rate of placental abruption and labor complications among patients with grade 3 placentas. A recent study has demonstrated an up to 6-fold increase in adverse perinatal outcomes (including placental abruption, low birth weight, low Apgar score, and perinatal death) among pregnancies where a grade 3 placenta was identified prior to 32 weeks of gestation.17 Thus, even though PL is not commonly used in the BPP, the recognition of a grade 3 placenta prior to 32 weeks should lead to a high index of suspicion for fetal jeopardy.
THE BIOPHYSICAL PROFILE: EARLY STUDIES

In the first prospective study using the BPP for management of 1184 high-risk patients, Manning and colleagues18 found a perinatal mortality rate of 5.06/1000, considerably lower than the rate of 63/1000 in historical controls (a similar high-risk population from the same region the previous year). Baskett and colleagues19 in 1984 published the results of a study where they used the BPP in managing 2400 high-risk pregnancies with 2485 fetuses. They found a perinatal mortality rate of only 1/1000 in those 1980 fetuses with a normal BPP score within 7 days of delivery, compared with an overall perinatal mortality rate of 9.2/1000. Subsequently, Manning and colleagues carried out the first randomized trial using the BPP and published the results in 1984. They compared the BPP in 375 patients with the NST in 360 patients and found that the BPP was more predictive of low Apgar scores.20 Although the BPPs sensitivity, specificity, positive predictive value and accuracy were higher than those of the NST, these differences between the BPP and the NST did not achieve statistical significance.20 After this, the same investigators studied 29 fetuses with an Apgar score of 0. They found that 14/29 of these perinates, almost half, died. Eleven were stillborn. In these, death occurred as soon as 30 minutes and as late as 11 days after the last test.21
THE BIOPHYSICAL PROFILE: IMPACT ON PERINATAL MORTALITY

Several studies have demonstrated the efficacy of the BPP in reducing perinatal mortality. In a study of 12620 high-risk patients who had 26357 biophysical scores, Manning and colleagues22 found that there were 93 perinatal deaths. Twenty-four of these occurred in structurally normal, nonisoimmunized fetuses (corrected perinatal mortality rate 1.9/1000). Eight of these fetuses died within 7 days of a normal BPP test (corrected false-negative rate of 0.634/1000). The uncorrected stillbirth rate was 3.64/1000 and the uncorrected neonatal death rate was 3.72/1000.22 These investigators found that the overall perinatal mortality ranged from 0.652/1000 births in patients with a BPP score of greater than or equal to 8 to 187/1000 births in pregnancies with a BPP score of 0, confirming that lower BPP scores are associated with higher perinatal mortality rates.22 The overwhelming majority of the BPPs (97.5%) were normal

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and only 0.76% had a BPP score of less than or equal to 4. The same investigators reported their experience with 44,828 BPPs performed in 19,921 high-risk pregnancies. The intrauterine death rate among fetuses without anomalies after a normal BPP was 0.726/1000 (14 deaths). Of these, approximately one-third resulted from cord prolapse. It is reasonable to assume these may not have been predicted by BPP assessment. If these deaths due to cord prolapse were excluded, the death rate could have been as low as 0.518/1000. Almost half the antepartum deaths occurred 5 to 7 days after a normal BPP result. It is as a result of this finding that BPPs are often performed twice a week in an attempt to further reduce perinatal mortality. In a study of 4148 fetuses, Baskett and coworkers23 found an overall perinatal mortality rate of 7.6/1000. Fetuses with a normal BPP (score 810) had a perinatal mortality rate of 1/1000, whereas fetuses with an equivocal score of 6 had a perinatal mortality of 31.3/1000. Even more importantly, fetuses with a BPP score of 0 to 4 had an extremely high perinatal mortality rate of 200/1000. These studies confirm that patients with normal biophysical testing have reduced perinatal mortality rates and that, conversely, perinatal outcomes worsen as BPP scores get lower.
THE MODIFIED BIOPHYSICAL PROFILE SCORE (AF AND NST)

Because of the excellent sensitivity of fetal NST for fetal acidemia, it has been proposed that this acute marker alone may be used for fetal assessment in combination with the AF volume assessment, a chronic marker. This combination, also known as the modified BPP, has been shown to have excellent false-negative rates that compare with that of the complete BPP.24,25
THE BIOPHYSICAL PROFILE AND PRETERM PREMATURE RUPTURE OF THE MEMBRANES

The fetal BPP has been used in the assessment and management of pregnancies complicated by PPROM. Vintzileos and colleagues compared BPPs in women with premature rupture of membranes (PROM) with women with intact membranes at gestational ages ranging from 25 to 44 weeks.10,26 They found no differences in total BPP scores between the 2 groups. They did find a higher frequency of reduced AF volume, reactive NSTs, and absent FBMs, however, in those patients with PROM.10 These same investigators subsequently performed BPPs every 24 to 48 hours on 73 women with PPROM who were not in labor and found that PPROM did not affect the BPP score.27 They compared the last BPP score with the infection outcome of the pregnancy (clinical chorioamnionitis, possible neonatal sepsis, and neonatal sepsis). They found that an abnormal BPP score (<8) was associated with an overall infection rate of 93.7%, whereas the overall infection rate in those pregnancies with a normal BPP score (8) was only 2.7%.27 They concluded that abnormal BPP scores were highly predictive of infection outcome. They only found this relationship between abnormal BPP testing and infectious morbidity when the interval between testing and delivery was 24 hours or less. In fetuses with severe infection as evidenced by neonatal sepsis (defined as infection confirmed by positive blood, urine, or cerebrospinal fluid culture), FMs and tone were compromised, whereas fetuses with possible neonatal sepsis (evidence of infection but negative cultures) had absent breathing movements and nonreactive NSTs. Because there was no difference in umbilical cord arterial pH values between infected and noninfected cases, the compromised biophysical activities were thought to be due to fetal infection rather than to acidemia. Correlations have also been found between both degree of oligohydramnios26 and

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nonreactive NSTs in PPROM and risk of intra-amniotic infection. Patients with PPROM and severe oligohydramnios (largest AF pocket <l cm) had the highest frequency of clinical chorioamnionitis (47.3%), possible neonatal sepsis (26.3%), and neonatal sepsis (31.5%), compared with 9.2%, 3.7%, and 1.8%, respectively, in patients with a largest AF pocket greater than 2 cm.26 In a retrospective analysis of 127 consecutive patients with PROM who had NSTs performed every 24 to 48 hours as part of the fetal BPP, those who initially had a reactive NST that subsequently converted to a nonreactive NST developed clinical intra-amniotic infection in almost 90% of cases.28 FBMs have also been shown to predict the absence of infection in patients with PPROM.29 Based on its ability to predict infection in PPROM, even in direct comparison to amniocentesis, Vintzileos and colleagues30 have suggested that daily BPPs could replace amniocentesis for prediction of infection in patients with PPROM. Several other studies have examined the relationship between BPP scores in PPROM and perinatal infection.3137 At least two-thirds of these studies have demonstrated a correlation between the two. In those studies that did find a correlation, daily BPP testing was performed. Intra-amniotic infection with Mycoplasma hominis is not necessarily associated with an abnormal BPP.31
THE BIOPHYSICAL PROFILE SCORE AND LONG-TERM OUTCOMES

There may be some relationship between abnormal BPP scores and long-term neurodevelopmental outcomes. Manning and colleagues,38 using 2 linked databases, attempted to determine if there was any relationship between the last BPP score in women having serial BPPs and the development of cerebral palsy at age 3 years. Of 22,336 high-risk pregnancies, 27 babies later developed cerebral palsy. These investigators found a relationship between last abnormal BPP scores and subsequent development of cerebral palsy. In a study of 84,947 live births, Manning and colleagues38 found that the rate of cerebral palsy among those 26,290 high-risk pregnancies that underwent BPP testing was 1.33 per 1000 live births, compared with 4.74 per 1000 live births in those 58,657 low-risk/mixed pregnancies that were not tested. They found an inverse, exponential, and highly significant relationship between the last BPP score and the development of cerebral palsy.38
MEDICATIONS AND THE BIOPHYSICAL PROFILE

Several medications used in pregnancy may affect the BPP. These include steroids, b-adrenergic agents, and magnesium sulfate. Rotmensch and colleagues39 studied 31 women between 27 and 32 weeks of gestation who were receiving 2 doses of betamethasone. They found an approximately 80% to 90% reduction in FBMs over 48 hours as well as a 50% reduction in fetal body movements. FT and AF volume remained stable. Half of all fetuses had a BPP score of 6/8 or 4/8; within 96 hours, however, all BPP scores had returned to normal. Similar reductions in fetal body and breathing movements after betamethasone administration were observed by Jackson and colleagues.40 These investigators also found, however, a reduction in AF volume in most patients, a finding they attributed to a reduction in FBMs. Deren and coworkers41 also found a reduction in fetal body movements and respiration after steroid administration. They also found more nonreactive NSTs after steroids. In all these studies, there was a reduction in BPP scores among some of the fetuses that received steroids. It is important to recognize this effect of steroids on the BPP in order to avoid unnecessary interventions. Magnesium sulfate is one of the most commonly used tocolytics in the United States. In a study of 31 fetuses (25 pregnancies), Gray and colleagues42 observed

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that intravenous magnesium sulfate did not significantly affect the BPP. In a study of 16 women with 22 fetuses at gestational ages of 26 to 34 weeks in spontaneous preterm labor, Peaceman and colleagues43 found that approximately half of the fetuses developed nonreactive NSTs and most fetuses had reduced FBMs after intravenous magnesium sulfate administration. Carlan and colleagues44 also found a reduction in FBMs, but no other changes in the BPP, in pregnancies when magnesium sulfate was administered for tocolysis. Hallak and colleagues45 found that both terbutaline and indomethacin, two other tocolytic agents in common use, increased FBMs, but had no other effects on the BPP.

LIMITATIONS OF THE BIOPHYSICAL PROFILE

The fetal BPP is a powerful tool in the assessment of fetal health. Yet, it is often misunderstood and misused.46 Perhaps the most important reason that BPP is misused relates to failure to consider the entire clinical scenario.46 For instance, a fetus at term with severe growth restriction should be delivered, despite the presence of a reassuring BPP score. Among the most common problems is using the total score without any consideration of the individual components.46 For instance, a score of 6/8 where 2 points are taken off for severe oligohydramnios is different from 6/8 where 2 points are taken off for lack of movement, but where fetal breathing is present. Another example is where a fetus with a reactive NST and normal AF but without obvious tone or movements during the examination is assigned a score of 4. In this case, however, both a reactive NST (the most sensitive acute marker) and normal AF volume (a chronic marker) are present, suggesting that the fetus is not compromised but that the absence of the other biophysical activities is due to periodicity. Unfortunately, such patients are often considered to have failed their BPP, and not infrequently, delivery is undertaken, often by cesarean, and possibly prematurely. It is inappropriate to use the same interval of testing for all cases. Although a BPP score is generally considered reliable for 1 week, certain high-risk conditions, including type 1 diabetes mellitus, growth restriction, or postdate pregnancies may require more frequent testing. Manning and colleagues22 observed, in a study of BPPs in 12,620 pregnancies, that half of the fetal deaths after reassuring BPP results occurred between 5 and 7 days after testing. They, therefore, suggested that twiceweekly testing may reduce mortality. The interval between testing should be individualized based on the circumstances of each particular case. It is widely recommended that when a test is nonreassuring, it should be repeated in 24 hours. This approach, however, is likely to lead to further compromise or even death in a fetus in jeopardy. The authors recommend that rather than repeating testing, extend the period of testing beyond 30 minutes. This helps differentiate between a compromised fetus and one where biophysical activities are absent due to periodicity. The BPP is often performed without an NST and considered adequate. This has the potential to miss fetuses at risk of death from cord accidents, however, even in the presence of a reassuring BPP score. FHR variable decelerations may be the only warning that a fetus is at risk for a cord accident. False reassurance may be provided if an NST is not performed. It is important, when the BPP is persistently nonreassuring, not to delay delivery due to concerns, such as an unfavorable cervix or preterm gestation. This may increase the risk of an adverse perinatal outcome.

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It is important that the BPP be performed correctly. Often, operator inexperience and faulty technique may lead to incorrect assessment of biophysical activities and inappropriate management decisions. Thus, AF measurements should be performed with the transducer perpendicular to the ground, and measurements should be made in cord-free pockets of AF. FBMs should be continuous and last at least 30 seconds. It is important to distinguish FBMs from fetal gasping movements. FMs should only be considered present if at least 3 rolling trunk movements are present in 30 minutes.
SUGGESTED ALGORITHM FOR BIOPHYSICAL PROFILE TESTING

One of the common questions asked about the BPP is when to start testing and with what frequency. The management of a pregnancy where the BPP score is not perfect is also a matter of controversy. Before going further, it is again crucial to emphasize that these cases need to be managed on an individual case-by-case basis. Thus, to answer the first question, the plan of antepartum testing must be appropriate for the individual pregnancy circumstances and the underlying pathophysiologic process. It is also important to appreciate the relationship between the individual biophysical activities and gestational age. So, starting biophysical testing at earlier gestational ages results in some activities not being present. If a physician does understand this limitation, however, BPP testing may be utilized. For instance, at 26 weeks, some fetuses have not yet developed FHR reactivity, and BPP interpretation must take this into consideration. BPP may have to be combined with other modalities of testing, including Doppler studies, depending on the particular pathophysiologic process. Generally, in fetuses with a high-risk condition where fetal growth is normal, BPP testing is started at approximately 32 weeks. The reason for this is that at 32 weeks, biophysical activities are all present in more than 95% of normal fetuses. BPP testing may be started earlier, however, in growth-restricted fetuses and in pregnancies complicated by PROM, bleeding, and a host of other conditions where the fetus is at more immediate risk, as long as the aforementioned limitations imposed by gestational age are recognized. The frequency of BPP testing also depends on the particular high-risk situation. A fetus with severe growth restriction may require BPPs daily or twice a day, whereas one undergoing surveillance for a history of hypertension may have a BPP twice weekly. Manning and colleagues reported that a few deaths occurred within 4 days of a normal BPP; therefore, it has been proposed that twice weekly testing may reduce the risk of stillbirth. Based on the fact that the combination of the nonreactive NST and absence of FBMs has excellent sensitivity for predicting the acidemic fetus, consistent with the gradual hypoxia concept, Vintzileos and coworkers recommended a modified fetal evaluation scheme for patients with intact membranes (Fig. 3). This scheme is based on the individual biophysical components rather than the score (see Fig. 3)4,46 Manning and coworkers47 have also observed that the NST, AF volume, and breathing movements are the most powerful predictors of fetal compromise. The authors suggested protocol includes assessment of an acute marker (NST or fetal breathing) and a chronic marker (AF volume). A reactive NST or fetal breathing lasting greater than 30 seconds (even in the presence of a nonreactive NST) makes fetal acidemia at the time of testing highly unlikely. In patients with uncontrolled diabetes, hyperglycemia may cause fetuses to exhibit FBMs even in the presence of (lactic) acidemia. For this reason, the authors recommend that the blood glucose should be checked in diabetic women at the time of the BPP assessment. When the NST is nonreactive, it becomes crucial to differentiate between fetal sleep and fetal acidemia. The presence of fetal breathing lasting greater than 30 seconds

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Fig. 3. An algorithm for the use of the modified fetal BPP in antepartum fetal surveillance. AFV, amniotic fluid volume; FBM, fetal breathing movements; NST, Non-Stress Test. (Data from Hanley ML, Vintzileos AM. Antepartum and intrapartum surveillance of fetal well being. Medicine of the fetus and mother. 2nd edition. Philadelphia: JB Lippincott, 1988. p. 793 and Vintzileos AM, Fleming AD, Scorza WE, et al. Relationship between fetal biophysical activities and umbilical cord gases. Am J Obstet Gynecol 1991;165:707.)

excludes acidemia. Therefore, if breathing is present and the AF volume is normal, the examination may end. When all biophysical activities (nonreactive NST, fetal breathing, FMs, and FT) are absent after 30 minutes of continuous observation, there is a high risk of fetal death; the fetus should be delivered promptly, regardless of gestational age. In a fetus with a nonreactive NST and FBMs, but in which body movements and tone are normal, the testing duration should be extended, with the goal of differentiating between fetal sleep and fetal compromise. The NST should be continued until it has become reactive pattern or until 120 minutes have elapsed. If the NST is still nonreactive after 120 minutes, and FMs and tone were seen initially, the real-time ultrasound examination should be repeated. If no fetal breathing is observed, and the gestational age is greater than 32 weeks, delivery may be considered. An alternative in selected cases is performing Doppler studies. In very preterm gestations (<32 weeks), if there is a persistently nonreactive NST (that is determined not to be due to FHR cyclicity) and absent fetal breathing, delivery should also be considered, with additional evaluation an option depending on individual circumstances. If FHR reactivity and body movements are present and normal, then

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expectant management is indicated. Oligohydramnios (defined as a largest AF pocket <2 cm or AF index <5 cm) and/or significant variable FHR decelerations suggest that that a fetus is at risk for cord accidents. If these are found, the authors recommend delivery if the pregnancy is at term or near term. Even in preterm gestations, these findings should always be considered concerning and may indicate a need for delivery in viable, structurally normal fetuses with intact membranes, regardless of gestational age. In very preterm gestations (<32 weeks) these pregnancies should be managed on a case-by-case basis, taking into consideration the results of Doppler velocimetry (if the underlying pathophysiology is reduced uteroplacental blood flow). Regardless, it is crucial to recognize that fetuses with growth restriction and oligohydramnios or variable decelerations are at increased risk of stillbirth, and that although prolonging gestation to improve maturity at birth, these fetuses may die while managed conservatively. In the presence of early severe fetal growth restriction, if delivery is not undertaken, the authors recommend frequent testing (every 24 hours) with Doppler studies to assist in deciding management.
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33. Yucel N, Yucel O, Yekeler H. The relationship between umbilical artery Doppler findings, fetal biophysical score and placental inflammation in cases of premature rupture of membranes. Acta Obstet Gynecol Scand 1997;76(6):5325. 34. Gauthier DW, Meyer WJ, Bieniarz A. Biophysical profile as a predictor of amniotic fluid culture results. Obstet Gynecol 1992;80(1):1025. 35. Roussis P, Rosemond RL, Glass C, et al. Preterm premature rupture of membranes: detection of infection. Am J Obstet Gynecol 1991;165(4 Pt 1): 1099104. 36. Miller JM Jr, Kho MS, Brown HL, et al. Clinical chorioamnionitis is not predicted by an ultrasonic biophysical profile in patients with premature rupture of membranes. Obstet Gynecol 1990;76(6):10514. 37. Vintzileos AM, Bors-Koefoed R, Pelegano JF, et al. The use of fetal biophysical profile improves pregnancy outcome in premature rupture of the membranes. Am J Obstet Gynecol 1987;157(2):23640. 38. Manning FA, Bondaji N, Harman CR, et al. Fetal assessment based on fetal biophysical profile scoring. VIII. The incidence of cerebral palsy in tested and untested perinates. Am J Obstet Gynecol 1998;178(4):696706. 39. Rotmensch S, Liberati M, Celentano C, et al. The effect of betamethasone on fetal biophysical activities and Doppler velocimetry of umbilical and middle cerebral arteries. Acta Obstet Gynecol Scand 1999;78(9):76873. 40. Jackson JR, Kleeman S, Doerzbacher M, et al. The effect of glucocorticosteroid administration on fetal movements and biophysical profile scores in normal pregnancies. J Matern Fetal Neonatal Med 2003;13(1):503. 41. Deren O, Karaer C, Onderoglu L, et al. The effect of steroids on the biophysical profile and Doppler indices of umbilical and middle cerebral arteries in healthy preterm fetuses. Eur J Obstet Gynecol Reprod Biol 2001;99(1):726. 42. Gray SE, Rodis JF, Lettieri L, et al. Effect of intravenous magnesium sulfate on the biophysical profile of the healthy preterm fetus. Am J Obstet Gynecol 1994; 170(4):11315. 43. Peaceman AM, Meyer BA, Thorp JA, et al. The effect of magnesium sulfate tocolysis on the fetal biophysical profile. Am J Obstet Gynecol 1989;161(3):7714. 44. Carlan SJ, OBrien WF. The effect of magnesium sulfate on the biophysical profile of normal term fetuses. Obstet Gynecol 1991;77(5):6814. 45. Hallak M, Moise K Jr, Lira N, et al. The effect of tocolytic agents (indomethacin and terbutaline) on fetal breathing and body movements: a prospective, randomized, double-blind, placebo-controlled clinical trial. Am J Obstet Gynecol 1992; 167(4 Pt 1):105963. 46. Vintzileos AM, Campbell WA, Nochimson DJ, et al. The use and misuse of the fetal biophysical profile. Am J Obstet Gynecol 1987;156(3):52733. 47. Manning FA, Morrison I, Harman CR, et al. The abnormal fetal biophysical profile score. V. Predictive accuracy according to score composition. Am J Obstet Gynecol 1990;162(4):91824 [discussion: 9247].