Intrauterine Fetal Demise

Bonnie J. Dattel MD

Basics

Description

Fetal death can occur at any GA.

Etiologies differ by GA; causes include:

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:

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:

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):

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 life-saving 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: Lippincott-Raven; 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.