Intrauterine Fetal Demise

Bonnie J. Dattel MD
Basics
Description
Fetal death can occur at any GA.
Etiologies differ by GA; causes include:
o

Chromosomal abnormalities

Fetal anemia secondary to alloimmunization or fetal-maternal

hemorrhage

Cord accidents

Fetal infection

Antiphospholipid antibody syndrome

Maternal thrombophilias

Obstetric disorders:

Preeclampsia

Abruption

IUGR secondary to utero placental insufficiency

Age-Related Factors
Certain conditions associated with perinatal risk are more common in advanced
maternal age:
Chromosomal aneuploidies
Preeclampsia/Chronic HTN

DM

Risk Factors
Risk factors are related to both exogenous and endogenous conditions:
Maternal age and increased risk for fetal aneuploidy and hypertensive diseases
Inherited conditions such as thrombophilias

DM and uteroplacental insufficiency

Occupations with high risk for exposure to certain infections (e.g., preschool
teachers and parvovirus)

Multiple gestations with TTTS

Genetics
Fetal aneuploidy is the most common reason for 1st trimester loss and should be
considered in cases of recurrent fetal loss (>3 consecutive spontaneous losses):
35% 1 of the parents has a balanced translocation
Unbalanced karyotype in up to 40% of abortus specimens

Recurrent aneuploidy especially if the 1st abortus was chromosomally

abnormal.

Pathophysiology
The pathophysiology, outside of aneuploidy, for IUFD depends on underlying
cause.
Uteroplacental insufficiency leading to fetal hypoxemia and ultimately
circulatory failure:
o

Chronic HTN

Preeclampsia/Eclampsia

DM

Abruptio placenta

Infections with overwhelming fetal sepsis and death, including fetal

anemia

Autoimmune disease/thrombophilia with placental

infarction/thromboses and relative uteroplacental insufficiency

Fetal-maternal hemorrhage with fetal anemia and circulatory failure

leading to death

Trauma with acute placental circulation disruption

Cord accidents (true knots, occult prolapse) with interrupted fetal

circulation and fetal hypoxemia leading to in utero death

Associated Conditions
Associated conditions that can increase the rate of in utero fetal death include:
Multiple gestations
Uterine anomalies

Any maternal disease that can interfere with uteroplacental circulation

Diagnosis
Signs and Symptoms
History
The medical history associated with fetal loss depends on trimester of pregnancy:
1st-trimester complaints often involve bleeding and cramping as a sign of fetal
loss.
2nd-trimester complaints can also include bleeding and cramping; however,
fetal movement may also no longer be recognized by the mother.

The most common complaint in the 3rd trimester is the loss of appreciated
fetal activity:
o

IUFD can occur with no maternal symptoms and may be found

incidentally.

Physical Exam
The physical findings of IUFD all involve the absence of a fetal heart rate,
regardless of GA. This absence should be confirmed by US.
3rd-trimester findings may also involve low AF levels and collapse of fetal
structures when visualized on US.

1st and 2nd-trimester losses may involve significant uterine bleeding requiring
surgical intervention.

Tests
In very early pregnancy, loss prior to the ability to visualize a fetal heart rate by US, a
falling -hCG level may be the only indicator of fetal loss.
Labs
Recommended laboratory evaluation when a late 2nd- or 3rd-trimester IUFD is
diagnosed:
Indirect Coombs test
Fetal karyotype

Kleihauer Betke

Serologic test for syphilis

Toxicology screen

Autopsy

Antiphospholipid antibodies

TORCH titers including parvovirus

Thrombophilia workup

Thyroid function tests

Glucose tolerance testing (HbA1C)

Imaging
US with failure to visualize fetal heart rate and activity is the gold standard for
diagnosis of IUFD.
Differential Diagnosis
The most important differential diagnosis when suspecting fetal death in the 1st
trimester is to exclude ectopic pregnancy, which can be life-threatening to the mother.
US evaluation of the adnexa
Serial -hCG levels to determine appropriate rise (or fall)
Infection
Infectious etiologies must always be considered with IUFD. TORCH viral
infection has been expanded to include parvovirus infection because of its
association with fetal anemia.
Infections cause fetal death by placental involvement causing a relative utero
placental insufficiency and by direct fetal infection leading to organ system
failure.

Hematologic
Fetal anemia either secondary to infection or direct fetal-maternal bleed should be
considered in fetal death.
Other causes of fetal anemia are alloimmunization and isoimmunization.
These cause profound fetal anemia via direct attack on fetal blood cells and
resulting bleeding (platelet consumption) or organ system failure (such as with
Rh isoimmunization or other red cell antigens).
Metabolic/Endocrine
The most common metabolic disease to lead to IUFD is DM. This occurs due to
placental failure generally in uncontrolled maternal diabetes.
Immunologic
New technologies have elucidated the relationship between maternal immunologic
dysfunction and fetal loss. These conditions generally result in uteroplacental
insufficiency that leads to fetal death:
Antiphospholipid antibody syndrome
Thrombophilias (Factor V Leiden, antithrombin III deficiency, prothrombin
gene mutation, lupus anticoagulant):
o

Placental infarctions or thromboses interfering with fetal circulation

Tumor/Malignancy
Malignancies are an uncommon cause of fetal death. Rarely, maternal tumors such as
melanoma can metastasize to the fetus and placenta.
Trauma
Blunt force trauma as from a motor vehicle accident is a known cause of
catastrophic fetal death. This usually results from an acute placental separation
and loss of maternal fetal circulation.
Maternal condition must be managed immediately.

Often associated with DIC

Drugs

Maternal drug use is also known to be associated with fetal death. The most
common association is between cocaine use and IUFD. This occurs secondary
to the blood flow changes that accompany cocaine ingestion and result in
placental abruption.
Chronic use of any substance, including nicotine, can result in placental
infarcts which, if extensive enough, can result in fetal demise.

Other/Miscellaneous
Virtually any underlying abnormality can result in fetal loss, however, these would be
rare entities.
P.399
Treatment
General Measures
Treatment of IUFD begins with its identification. Further treatment measures are
dependent on GA age of the discovery.

Pregnancy-Specific Issues
Mothers experiencing a fetal death most desire to know the cause of the death. This is
extremely important in counseling for future pregnancies. An autopsy and placental
pathology are the 2 most useful pieces of information for the pregnant woman who
has had an IUFD.
By Trimester
1st- and early 2nd-trimester fetal death can be treated either conservatively with
uterine evacuation agents such as misoprostol or surgically with D&C. In the 3rd
trimester, induction of labor with prostaglandins or oxytocin is the mainstay of
treatment.
Risks for Mother
Risks for the mother involve the associated risks of the treatments involved. These
include:
Blood loss, surgical trauma, infection
In cases of acute abruption, maternal DIC can be life-threatening and requires
intensive maternal care.

Rarely, cases of prolonged fetal death can be associated with maternal DIC
and require prompt and aggressive intervention to save the mother.

Risks for Fetus

After a fetal death, the information gleaned toward determining the cause of the loss
can be invaluable for prevention of the loss of future fetuses.
Special Therapy
Complementary and Alternative Therapies
In addition to the use of agents for induction of labor or uterine evacuation, attention
must be paid to the psychological well-being of the mother who has experienced the
loss. Regardless of GA, IUFD is accompanied with profound psychological
components. The mother should receive appropriate bereavement counseling and
close follow-up to detect the development of associated depressive disorders.
Medication (Drugs)
The medications used for induction of labor are similar to those used for IUFD.
Caution must be used to avoid uterine rupture.
Surgery
In general, delivery of a dead fetus by cesarean section should be reserved for lifesaving circumstances in the mother or the failure to accomplish safe vaginal delivery.
Followup
Disposition
Issues for Referral
Women who have experienced an IUFD should receive appropriate
postpartum follow-up.
An evaluation in the postpartum period should include not only the routine
physical examination but a discussion of the events that occurred and
information that has been obtained in the workup of the fetal death.

Evaluation for depression should be part of every follow-up exam.

Referral to parents' groups or individual counseling may be helpful.

Prognosis

Prognosis for recovering from a fetal loss is usually excellent. Most women
recover from sporadic 1st-trimester losses relatively easily, as they can be
assured that 90% of women with a single early pregnancy loss go on to have
normal pregnancies in the future.
For women with recurrent pregnancy loss or 3rd-trimester losses, the recovery
time frame is longer (monthsyears). For many women there are trigger dates,
such as the date of the loss or the due date of the pregnancy. Many of these
women will benefit from outpatient counseling.

Complications
The main complications of IUFD are related to the underlying cause. In women with
acute abruption, DIC, and circulatory collapse long-term sequelae may occur,
involving renal failure as in shock/trauma cases. These are rare, however.
Patient Monitoring
Patients should be monitored during labor as are parturients with a live fetus.
Patients with acute abruption and DIC require intensive surveillance and blood
product replacement.

Postpartum, patients should be monitored and screened for depression.

Fetus

No fetal monitoring is required in cases of IUFD.

However, in subsequent pregnancies, antenatal fetal surveillance should be
instituted near the time of a 3rd-trimester loss.

Pregnancies complicated by prior utero placental insufficiency, regardless of

etiology, should have serial US for fetal growth.

Pregnancies complicated by thrombophilia should receive anticoagulant

therapy.

These pregnancies are best referred to MFM specialists due to their high-risk
nature.

Bibliography
Reece EA, et al., eds. Medicine of the Fetus and Mother. Philadelphia: LippincottRaven; 1999.
Creasey RK, et al. Maternal-Fetal Medicine, 4th ed. Philadelphia: W.B. Saunders;
1999.
Miscellaneous
Clinical Pearls
The occurrence of an IUFD is a life-altering experience for a pregnant woman.
Considerations at this time include patient bereavement, appropriate delivery, and
evaluation for discoverable causes of the demise that may impact future reproduction.
Abbreviations
AFAmniotic fluid
DICDisseminated intravascular coagulation
GAGestational age
hCGHuman chorionic gonadotropin
IUGRIntrauterine growth restriction
IUFDIntrauterine fetal demise

 MFMMaternal-fetal medicine
TORCHToxoplasmosis, other, rubella, cytomegalic virus, and herpes
TTTSTwin-twin transfusion syndrome
Codes
ICD9-CM
646.4 Intrauterine death
Patient Teaching
All pregnant women should be counseled regarding normal fetal activity,
avoidance of high-risk behaviors (including smoking and substance use), avoiding
infectious complications (parvo exposure, Listeria exposure), and symptoms to report
to their care providers that could signal fetal danger.
Prevention
The prevention of IUFD rests on the provision of prenatal care to identify pregnancies
at risk or in jeopardy. Careful evaluation of a prior fetal death can provide invaluable
information to allow appropriate intervention and surveillance of future pregnancies
to prevent loss.