Evaluation of Fetal Death

Author: James L Lindsey, MD; Chief Editor: Carl V Smith, MD

Definition of Fetal Death
The loss of a fetus at any stage is a fetal demise. According to the 2003 revision of the Procedures for Coding Cause of Fetal Death Under ICD-10, the National Center for Health Statistics defines fetal death as "death prior to the complete expulsion or extraction from its mother of a product of human conception, irrespective of the duration of pregnancy and which is not an induced termination of pregnancy. The death is indicated by the fact that after such expulsion or extraction, the fetus does not breathe or show any other evidence of life, such as beating of the heart, pulsation of the umbilical cord, or definite movement of voluntary muscles. Heartbeats are to be distinguished from transient cardiac contractions; respirations are to be distinguished from fleeting respiratory efforts or gasps." In the United States, the term stillbirth or fetal demise does not have a standard definition. For statistical purposes, fetal losses are classified according to gestational age. A death that occurs prior to 20 weeks' gestation is usually classified as a spontaneous abortion; those occurring after 20 weeks constitute a fetal demise or stillbirth. Many states use a fetal weight of 350 g or more to define a fetal demise. Although this definition of fetal death is the most frequently used in medical literature, it is by no means the only definition in use. Even within the United States, the differences in the definitions used are substantial. In addition, not all states interpret the weeks of gestation in the same manner. In California, 20 weeks' gestation is worded "twenty utero gestational weeks" and has therefore been interpreted to be 23 weeks from the last menstrual period. (Implantation in the uterus does not occur until 1 wk after fertilization.) Physicians must check the reporting requirements for the state(s) in which they practice.

Frequency of Fetal Death
In 2005, data from the National Vital Statistics Report showed a US national average stillbirth rate of 6.2 per 1000 births.[1] Worldwide, this rate varies considerably depending on the quality of medical care available in the country in question and the definitions used for classifying fetal deaths. Underreporting in developing nations is common, which makes comparisons even more difficult. In 2009, the estimated global number of stillbirths was 2.64 million (uncertainty range, 2.143.82 million).[2] The worldwide stillbirth rate declined by 14.5% from 22.1 stillbirths per 1000 births in 1995 to 18.9 stillbirths per 1000 births in 2009.

In women with fetal death before 28 weeks' gestation. and combined administration of misoprostol for second-trimester induction in women without a uterine scar and found that the superior regimen was misoprostol at 400 mcg vaginally every 6 hours. An inability to obtain fetal heart tones upon examination suggests fetal demise. Early fetal demise may be managed with laminaria insertion followed by dilatation and evacuation. vaginal. fibrinogen levels may drop. In women with fetal death after 28 weeks' gestation. In women with no uterine scar. while others wish to delay induction for a period of hours or days until they are emotionally prepared. lower doses should be used. Patients with a history of a prior cesarean delivery should be treated cautiously because of the risk of uterine rupture. In 2003. Labor induction should be offered after diagnosis. Often. This is rarely a problem because of earlier recognition and induction. and induction can be continued with oxytocin. leading to a coagulopathy. misoprostol (ie. this is not diagnostic and death must be confirmed by ultrasonographic examination. and/or oxytocin (preferred in women with prior uterine surgery). mechanical ripening can be performed with a Foley catheter. misoprostol (25 mcg q4-6h) may be administered for ripening after 28 weeks’ gestation. induction may be accomplished using prostaglandin E2 vaginal suppositories (10-20 mg q4-6h).[3] A meta-analysis of the use of misoprostol for induction in the second and third trimester showed efficacy of .Diagnosis of Fetal Death History and physical examination are of limited value in the diagnosis of fetal death. The American College of Obstetricians and Gynecologists (ACOG) guidelines for induction of labor states that prostaglandin E2 and misoprostol should not be used in women with a history of a prior uterine incision because of the risk of uterine rupture. the patient should be informed of her condition. allowing the mother to see the lack of cardiac activity helps her to accept the diagnosis. just as in any birth following cesarean delivery (see Vaginal Birth After Cesarean Delivery). In some cases of twin pregnancies. Patient responses vary in regard to this recommendation. Induction may be accomplished with preinduction cervical ripening followed by intravenous oxytocin (see Cervical Ripening).[3] For women with a prior cesarean delivery. When a dead fetus has been in utero for 3-4 weeks. prostaglandin E1) vaginally or orally (400 mcg q4-6h). however. Fetal demise is diagnosed by visualization of the fetal heart and the absence of cardiac activity. induction after the death of a twin may be delayed to allow the viable twin to mature. In most patients. the only symptom is decreased fetal movement. Dickinson and Evans reported on the efficacy of oral. some wish to begin induction immediately. Management of Fetal Death Once the diagnosis of fetal demise has been confirmed.

Small size for gestational age and abruption were the highest-ranking pregnancy disorder risk factors for stillbirth.multiple routes (vaginal. epidural anesthesia should be offered.[6] Advanced maternal age (>35 y) and maternal smoking were also significant. See the image below for an example of a checklist that can be used in the management of fetal demise. This is an example of a checklist to be used following fetal death.9% of fetal death to placental pathology overall. Preexisting diabetes and hypertension are also important contributors to stillbirth.[5] A meta-analysis of 96 population-based studies found that maternal overweight and obesity was the highest-ranking modifiable risk factor for stillbirth. Higher doses of narcotics are available to the patient and often a morphine or Dilaudid PCA is sufficient for successful pain control. sublingual). One prospective study attributed 64. Courtesy of Santa Clara Valley Medical Center.[4] Pain management in patients undergoing induction of labor for fetal demise is usually easier to manage than in patients with live fetuses. In cases where a cause is clearly identified. oral. The same study noted higher rates of fetal demise secondary to placental pathology at late gestational age. Causes of Fetal Death The etiology of fetal demise is unknown in 25-60% of all cases. Should a patient desire superior pain control to intravenous narcotics. Maternal       Prolonged pregnancy (>42 wk) Diabetes (poorly controlled) Systemic lupus erythematosus Antiphospholipid syndrome Infection Hypertension . the cause of fetal death can be attributable to fetal. or placental pathology. and dosages (100-400 mcg). frequencies (every 3-12 h). maternal.

parvovirus B19. .        Preeclampsia Eclampsia Hemoglobinopathy Advanced maternal age Rh disease Uterine rupture Maternal trauma or death Inherited thrombophilias Fetal       Multiple gestations Intrauterine growth restriction Congenital abnormality Genetic abnormality Infection (ie. which is used at Santa Clara Valley Medical Center. The following image is an example of such a checklist. and placenta as well as to ensure that the emotional needs of the family are met. fetus. use of a checklist is helpful to prevent oversights in the evaluation of the mother. Listeria) Hydrops Placental       Cord accident Abruption Premature rupture of membranes Vasa previa Fetomaternal hemorrhage Placental insufficiency Risk factors (weak predictive value)         African American race Advanced maternal age History of fetal demise Maternal infertility History of small for gestational age infant Small for gestational age infant Obesity Paternal age Evaluation of Fetal Demise The time following a fetal death is extremely difficult for both the family and the health care providers. CMV. In this stressful time.

In an effort to better understand the underlying pathophysiology that leads to fetal demise and thereby create appropriate interventions. experts proposed a uniform international classification system and recommended a complete stillbirth workup for every case of fetal demise. Currently. The Stillbirth Collaborative Research Network currently has ongoing studies. footprints.[7] Up to 60% of stillbirths have no identifiable etiology. pregnancy management. This usually includes referrals for counseling. Although uncommon. which will hopefully define the optimal diagnostic evaluation for this difficult clinical problem. a limited fetal evaluation should be discussed with the family. true knot. which tests are most effective in evaluating a fetal demise have not been agreed upon. Attempting to determine the cause of fetal death remains important because it may influence estimates of recurrence and future preconceptional counseling. Spiritual support is an important resource during such difficult times and should always be offered to patients and their families. prenatal diagnostic procedures. or a lock of hair. authorities vary in their recommendations. entanglement. postmortem MRIs can . The decision to proceed with an autopsy must be made by the parents and informed consent is necessary. In such cases. and other resources. Courtesy of Santa Clara Valley Medical Center. Another useful resource is a grief packet that can be given to the parents following the demise. Therefore. Most of the testing recommendations in the past have been based on expert opinion rather than scientific studies. or previously known lethal karyotype. A container or folder can be included so that the family can preserve keepsakes such as photos.This is an example of a checklist to be used following fetal death. The most important part of the workup of a fetal demise is the autopsy of the fetus. For example. testing can be limited to toxicology screening and possibly a thrombophilia workup. prolapse. Many institutions use a selective workup based on clinical findings. Causes deemed fairly obvious include cord accident (ie. With parents who are resistant to the idea of a complete autopsy. and neonatal management. either no further testing or limited testing is performed. If severe clinical abruption is present. tight nuchal cord). no further workup is necessary. anencephaly. support groups. when clinical findings strongly suggest a cause for the fetal demise at Santa Clara Valley Medical Center.

has growth retardation. Chromosomal analysis should also be considered in patients with multiple pregnancy losses. or has anomalies or other signs of chromosomal abnormality. Again. Fetal karyotype can be obtained from a sample of amniotic fluid (preferred).) Radiographs.provide valuable information in the evaluation of a fetus when an autopsy cannot be performed. It is especially important if the fetus is dysmorphic. The placenta and the membranes should be carefully examined. A summary of the protocol for the fetus and placenta is as follows:       Careful inspection Placental cultures for suspected listeria infection (To obtain placental cultures. This is an example of a checklist to be used following fetal death. especially with a history of secondand third-trimester losses or when a parent has a balanced translocation or mosaic chromosomal pattern. an algorithm or checklist is helpful to avoid omissions (see image below). if indicated Autopsy MRI. separate the amnion and the chorion and submit a culture specimen using Stuart media. Many authorities (including the ACOG committee on evaluation of stillbirth) recommend obtaining this test in every fetal demise. Fetal karyotype should be considered in all cases. is hydropic. Courtesy of Santa Clara Valley Medical Center. including cultures. fetal blood. or fetal tissue (skin or fascia lata). if no autopsy Fetal karyotype . This inspection is even more important if the family declines an autopsy.

Inherited Thrombophilias in Pregnancy. most authorities have recommended obtaining TORCH (toxoplasmosis. repeat testing for diabetes is probably not necessary. The value of thrombophilia testing in any circumstance in obstetrics has recently been questioned. However. FT4) Urine toxicology screening The above tests have traditionally been a part of an evaluation for the etiology of fetal demise. these tests are inexpensive and normal results may be reassuring to the patient. The frequency is higher in developing countries. TSH. or significant intrauterine growth retardation. A multicenter. Additional tests that should be considered are as follows:       Antibody screening CBC count with platelet count Kleihauer-Betke test Laboratory tests for antiphospholipid syndrome: See Antiphospholipid Antibody Syndrome and Pregnancy. Infection is a cause of fetal demise. is now recommending inherited thrombophilia testing only in selected cases. there is no recommendation to screen for inherited thrombophilias with pregnancy loss. . severe preeclampsia in the second or early third trimester. Authority opinions vary as to which panel of tests is appropriate.[9] In a more recent ACOG Practice Bulletin.[11] Infection: See Bacterial Infections and Pregnancy. Inherited thrombophilias are common in the general population but are probably rare causes of fetal demise. observational cohort study concluded that there was no association between prothrombin G20210A mutation and pregnancy loss.[8] The current ACOG Practice Bulletin. a more selective approach is to limit testing to patients who have a history of venous thrombosis. prospective. abruption. rubella. severe placental pathology. abruption. Traditionally. Inherited thrombophilia panel o The enthusiasm for laboratory testing for inherited thrombophilias for adverse pregnancy outcome is waning. Similarly.[10] o While some authorities recommend maternal testing in all cases of fetal demise. preeclampsia. or SGA neonates in a low-risk population. Autopsy and histologic evaluation of the placenta is probably the best way to document an infectious etiology for a fetal demise. If diabetes screening has been performed during the prenatal period. Management of Stillbirth. if the patient has no signs or symptoms of thyroid disease. thyroid dysfunction is unlikely to be the cause of the demise.Maternal Studies Maternal studies that should also be considered during the workup of a fetal demise include the following:     Diabetes testing using hemoglobin A1C and a fasting blood glucose Syphilis screening using the VDRL or rapid plasma reagent test Thyroid function testing (ie. cytomegalovirus. positive family history.

for antiphospholipid testing Anti-B 2 -glycoprotein 1 IgG or IgM antibodies Useful in some circumstances         Factor V Leiden Prothrombin mutation Protein C. it is questionable whether cytomegalovirus virus causes fetal demise. those with intrauterine growth restriction. In addition. In reality. and (4) Toxoplasmosis gondii (acute and chronic titers) and (5) syphilis. protein S. Silver and the Stillbirth Collaborative Research Network.and herpes simplex virus) antibody titers. and antithrombin III deficiency TSH Hemoglobin A1C TORCH titers Placental cultures Testing for other thrombophilias Developing technology     Comparative genomic hybridization Testing for single gene mutations Testing for confined placental mosaicism Nucleic acid-based testing for infection . (3) parvovirus (acute and chronic titers). (2) rubella virus (acute and chronic titers. This summary has been modified as more recent studies have become available. and T gondii to those patients in whom clinical findings suggest the possibility of intrauterine infection (ie. rubella virus. microcephaly). consider testing for (1) cytomegalovirus (acute and chronic titers). If no obvious cause for the demise is established or if clinical signs or symptoms suggest infection. this is rarely helpful in the diagnosis. This is adopted with permission from the work of Dr. if not immune). for antiphospholipid testing Anticardiolipin anticoagulant. Commonly accepted tests             Thorough maternal history Fetal autopsy Placental evaluation Karyotype Indirect Coombs test Serologic test for syphilis Testing for fetal-maternal hemorrhage (Kleihauer-Betke or other) Urine toxicology screen Parvovirus serology Lupus anticoagulant. Robert M. Testing for Fetal Demise The following provides a summary of the current status of testing for fetal demise. A more cost-effective approach is to limit testing for cytomegalovirus.

Fetal death of unknown cause is a special problem. Most patients find increased fetal surveillance with the next pregnancy reassuring. patients are naturally anxious.[12] Although recurrent fetal loss is uncommon. a provider has difficulty determining risk of stillbirth for any particular pregnancy. The ACOG recommends antepartum testing starting at 32-34 weeks' gestation in an otherwise healthy mother with history of stillbirth. frequent ultrasound is reassuring. Because a large number of etiologies of fetal demise exist. In some cases. For patients who have experienced earlier loss. even though such testing is not clearly beneficial. Genetic screening and detailed ultrasound can evaluate future pregnancies. Optimal management of chronic medical conditions is important prior to the next pregnancy.Management of Future Pregnancy If a particular medical problem is identified in the mother. the patient can be assured that recurrence is very unlikely. it should be addressed prior to conception. For example. such as cord occlusion. Preconceptional counseling is helpful if congenital anomalies or genetic abnormalities are found. . tight control of blood glucose prior to conception can substantially reduce the risk of congenital anomalies in the fetus. Evidence-based models such as Active Management of Risk In Pregnancy At Term (AMOR-IPAT) are being created in an effort to better estimate this risk.[9] Weekly biophysical profile or fetal heart rate testing can be combined with maternal kick counts in the third trimester.

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