Evaluation of Fetal Death

Updated: Jun 05, 2023
  • Author: Michael G Ross, MD, MPH; Chief Editor: Carl V Smith, MD  more...
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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."

A more recent definition of fetal death, according to the US National Center for Health Statistics, is the delivery of a fetus showing no signs of life as indicated by the absence of breathing, heartbeats, pulsation of the umbilical cord, or definite movements of voluntary muscles. [1]

In the United States, the term stillbirth or fetal demise does not have a standard definition. Stillbirth is the preferred term among parent groups, and this term is increasingly used in place of fetal death. [2]

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 define a fetal demise using a fetal weight of greater than or equal to 350 g, a value which represents the 50th percentile for weight at 20 weeks of gestation.

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 week after fertilization.) Physicians must check the reporting requirements for the state(s) in which they practice. 

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Frequency of Fetal Death

The National Center for Health Statistics reported a total of 20,854 fetal deaths at 20 weeks of gestation or more in the United States in 2020. [3] The US fetal mortality rate was 5.74 fetal deaths at 20 weeks of gestation or more per 1000 live births and fetal deaths. With minor fluctuations, the total US fetal mortality rate has declined 23% since 1990 (7.49). 

In 2020, the fetal mortality rate in the United States was highest for non-Hispanic Native Hawaiian or Other Pacific Islander (10.59) and non-Hispanic Black (10.34) women and lowest for non-Hispanic Asian women (3.93), followed by non-Hispanic White (4.73) and Hispanic (4.86) women. [3]  Many factors, including genetics, environment, stress, social issues, access to and quality of medical care and behavior, contribute to racial disparity in stillbirth. [4]  Implicit and explicit bias and racism are also implicated in many health disparities, including perinatal morbidity and mortality. [5]

The fetal mortality rate for twins (12.12) was more than twice that for singletons (5.51) (Table 1). The rate for triplet or higher-order deliveries (28.72) was more than five times that for singletons. [3]  The risk of stillbirth increases in all twins with advancing gestational age, and it is significantly greater in monochorionic as compared with dichorionic twins. [6]

Worldwide, the rate of fetal death varies considerably depending on the quality of medical care available in the country in question and the definitions used for classifying fetal deaths. Globally in 2019, an estimated 2.0 million babies (90% uncertainty interval [UI], 1.9-2.2) were stillborn at 28 weeks or more of gestation, with a global stillbirth rate of 13.9 stillbirths (90% UI, 13.5-15.4) per 1000 total births. Stillbirth rates were highest in west and central Africa (22.8 stillbirths per 1000 total births) and lowest in western Europe (2.9 stillbirths per 1000 total births). [7]  

The World Health Organization (WHO) launched the Every Newborn Action Plan (ENAP) in 2014 to provide a road map of strategic actions for ending preventable newborn mortality and stillbirth. [8] By 2030, ENAP targets a stillbirth rate of ≤12 neonatal deaths per 1000 live births. As of 2020, 56 countries were at risk of missing the ENAP stillbirth rate target, of which 45 need to more than double their progress to achieve the target by 2030. [9]

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Diagnosis of Fetal Death

History and physical examination are of limited value in the diagnosis of fetal death. In most patients, the only symptom is decreased fetal movement. An inability to obtain fetal heart tones upon examination suggests fetal demise; however, this is not diagnostic and death must be confirmed by ultrasonographic examination.

Fetal demise is diagnosed by visualization of the fetal heart and the absence of cardiac activity. Stillbirth is indicated by no signs of life after delivery, including absence of heartbeat umbilical cord pulsations, breathing, or voluntary muscle movements.  

 

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Management of Fetal Death

Once the diagnosis of fetal demise has been confirmed, the patient should be informed of her condition. Often, allowing the mother to see the lack of cardiac activity helps her to accept the diagnosis. The method and timing of delivery after a stillbirth depend on the gestational age at which the death occurred, maternal obstetric history (eg, previous hysterotomy), and maternal preference. [2]

Termination of pregnancy should be offered when the diagnosis of fetal death occurs in a singleton gestation. Patient responses vary in regard to this recommendation; some wish to begin induction immediately, while others wish to delay induction for a period of hours or days until they are emotionally prepared. The timing of delivery is not critical unless there is an associated condition that places maternal health at risk such as preeclampsia, HELLP syndrome, placental abruption, or coagulopathy. Coagulopathies associated with prolonged fetal retention are uncommon, but one study found that 4% of women with IUFD develop coagulopathy without an apparent cause. [10]  This risk can be minimized with earlier recognition and expedited delivery if there are abnormal laboratory parameters, such as low platelet count, prolonged prothombin time, or low fibrinogen levels.

Fetal death may also occur in multiple gestations, and the management approach is more complex due to the presence of a surviving fetus. In the second trimester and third trimester, up to 5% of twins and 17% of triplets undergo death of one or more fetuses.  [11]  Subsequent to the demise of one twin after 14 weeks, a systematic review found that the risk of death in the co-twin is 41% in monochorionic gestations and 22% in dichorionic gestations. [12]  The risk of neurologic abnormality in the surviving twin is greater in monochorionic gestations (29%) versus dichorionic gestations (10%). [12]   Morbidity and mortality in monochorionic twins is greater because of bidirectional placental vascular anastomoses. Exsanguination into the low-pressure vascular system of the deceased twin can lead to acute hypotension, anemia, and ischemia in the surviving co-twin, resulting in neurologic brain injury or death. [13]  

Following fetal death in an otherwise uncomplicated dichorionic twin gestation, the risk of morbidity and mortality to the surviving fetus is very low and early delivery is not recommended. While fetal death of a co-twin in a monochorionic pregnancy is associated with significant morbidity and mortality in the other fetus as noted above, immediate delivery of the co-twin is not usually recommended because the benefit is unclear and there is potential harm from iatrogenic preterm delivery. [14]  However, ultrasound and magnetic resonance imaging evaluation of the surviving co-twin may be considered to assess for signs of brain injury, such as ventriculomegaly, white matter lesions, or intracranial hemorrhage.  In the absence of a maternal indication or another fetal indication for prompt delivery, delivery before 34 weeks of gestastion is not recommended following the death of one fetus in a monochorionic twin gestation. [15]   

Methods for delivery of the stillborn fetus typically include dilation and evacuation or induction of labor. In the second trimester, dilation and evacuation can be offered if an experienced healthcare provider is available. [2]  The patient should be aware that dilation and evacuation limits autopsy evaluation of macroscopic fetal abnormalities and precludes seeing or holding the fetus. However, between 13 and 24 weeks of gestation, induction of labor is less effective than dilation and evacuation and has higher complications rates. One study showed that among women undergoing labor induction, 24% experienced one or more complications, compared to 3% of women undergoing dilation and evacuation (adjusted risk ratio, 8.5; 95% CI, 3.7-19.8). [16]  The main complication with labor induction at 13-24 weeks is retained placenta, with need for dilation and curretage or manual removal. 

If the patient desires labor induction and does not have any contraindication to vaginal delivery, there are a few different methods available, which vary based on gestational age at the time of fetal demise. Before 28 weeks of gestation, vaginal misoprostol appears to be the most efficient method of induction, regardless of cervical Bishop score, although high-dose oxytocin infusion also is an acceptable choice.  [2]  The typical dosages for misoprostol are 400-600 mcg vaginally every 3-6 hours, and dosages lower than 400 mcg have decreased efficacy. Mifepristone (either 200 or 600 mg orally) can be used as an adjunct to misoprostol, and it reduces the time to delivery when compared with misoprostol alone. [17]  It can be administered 24-48 hours before initiation of induction with misoprostol. After 28 weeks of gestation, induction of labor should be managed according to usual obstetric protocols.

Patients with a history of a prior cesarean delivery should be treated cautiously because of the risk of uterine rupture, just as in any birth following cesarean delivery (see Vaginal Birth After Cesarean Delivery). Both induction of labor and dilation and evacuation remain options for women with a previous hysterotomy. In a study from the Stillbirth Collaborative Research Network, 45 patients with stillbirth and a history of previous cesarean delivery underwent induction of labor. [18]  Of these, 91% (41/45) delivered vaginally, four patients required cesarean delivery, and two (4.4%) experienced uterine rupture.  One uterine rupture occurred after misoprostol induction at 22 weeks, while the other occurred after oxytocin induction at 37 weeks. For women with stillbirth and a history of previous cesarean who presented in spontaneous labor, 74.1% (20/27) delivered vaginally with no cases of uterine rupture. [18]

In women with prior cesarean delivery, randomized trials support the use of vaginal misoprostol as a medical treatment to terminate nonviable pregnancies before 24 weeks of gestation. [19] However, for women between 24 weeks and 28 weeks of gestation with prior hysterotomy, further research is needed as lower doses of misoprostol (200 mcg per dose) may be preferred. [20]  Women with a previous hysterotomy and fetal demise after 28 weeks of gestation should undergo induction of labor per standard obstetric protocols for trial of labor after cesarean (see ACOG Practice Bulletin No. 205, Vaginal Birth After Cesarean Delivery) rather than misoprostol administration. Mechanical ripening can be performed with a Foley catheter, and induction can be continued with oxytocin.

Pain management in patients undergoing induction of labor for fetal demise is an important part of patient care. Often, a morphine or hydromorphone patient-controlled analgesia device is sufficient for successful pain control. Should a patient desire superior pain control to intravenous narcotics, epidural anesthesia should be offered.

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Causes of Fetal Death

The etiology of fetal demise is unexplained in 25-60% of all cases. An unexplained stillbirth is a fetal death that cannot be attributed to an identifiable etiology due to lack of sufficient information or because the cause cannot be determined using existing diagnostic modalities. In cases where a cause is clearly identified, the cause of fetal death can be attributable to fetal, maternal, or placental pathology. A systematic review of global causes of stillbirth from over 50 countries found that unexplained fetal deaths were the most common in low, middle, and high-income countries (31.2-43.7%). [21] Among stillbirths in which an etiology could be determined, the most common cause in low-income countries was either infection (15.8%) or hypoxic peripartum death (11.6%), whereas the most common cause in middle- and high-income countries was attributed to a placental condition (13.7-14.4%). Antepartum hemorrhage was also a common cause of stillbirth globally (8.4-9.3%).

A meta-analysis of 96 population-based studies found that maternal overweight and obesity was the highest-ranking modifiable risk factor for stillbirth. [22, 23, 24] Advanced maternal age (>35 y) and maternal smoking were also significant. Small size for gestational age and abruption were the highest-ranking pregnancy disorder risk factors for stillbirth. Preexisting diabetes and hypertension are also important contributors to stillbirth. [25]  Additionally, there are racial disparities in reported stillbirth cases in the United States. A population study found that a higher proportion of stillbirths in non-Hispanic Black women compared with non-Hispanic White and Hispanic women were associated with obstetric complications (43.5% vs 23.7%; difference, 19.8%; 95% CI, 9.7%-29.9%; P< .001) and infections (25.2% vs 7.8%; difference, 17.4%; 95% CI, 9.0%-25.8%; P< .001). [26]  

Infection is a common cause of stillbirth globally and may lead to fetal demise owing to severe maternal illness, placental effects, or direct fetal infection. Maternal sepsis due to bacterial infection, or viral etiology such as COVID-19, may have life-threatening systemic effects, with severe hypotension and end-organ injury contributing to fetal death. A large population-based study in the United States found that infection-related stillbirth occurred at an earlier gestational age compared with non-infection-related stillbirth (median gestational age, 22 vs 28 weeks; P = .001). [27]  The predominant species were Escherichia coli (29%), group B streptococcus (GBS) (12%), and enterococcus species (12%). The most common nonbacterial organism associated with stillibrth cases was cytomegalovirus (8%), and other etiologies included parvovirus, syphilis, and herpes virus. 

Maternal

Maternal causes of fetal death are as follows:

Fetal

Fetal causes include the following:

  • Multiple gestations

  • Intrauterine growth restriction

  • Congenital abnormality

  • Genetic abnormality

  • Infection (ie, parvovirus B19, CMV, Listeria)

  • Hydrops

Placental

Placental causes of fetal death are as follows:

  • Cord accident

  • Abruption

  • Premature rupture of membranes

  • Vasa previa

  • Fetomaternal hemorrhage

  • Placental insufficiency

Estimated rates of stillbirth by condition 

Table. Estimated Rate of Stillbirth by Condition [2] (Open Table in a new window)

Condition

Estimated rate of

stillbirth per 1000

Diabetes, diet controlled 6-10
Diabetes, on insulin 6-35
Chronic hypertension 6-25
Preeclampsia without severe features 9-51
Preeclampsia with severe features 12-29
Fetal growth restriction 10-47
Twin gestation 12
Triplet gestation 34
Oligohydramnios 14
Late-term pregnancy >41 weeks 14-40
Previous stillbirth 9-20
Decreased fetal movement 13
Systemic lupus erythematosus 40-150
Renal disease 15-200
Cholestasis 12-30
Maternal age 35-39 years 11-14
Maternal age 40 years or greater 11-21
Maternal age less than 20 years 7-13
Black maternal race 12-14
Assisted reproductive technology 12
BMI 30 or greater 13-18
Smoking >10 cigarettes per day 10-15

 

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Evaluation of Fetal Demise

The time following a fetal death is extremely difficult for both the family and the health care providers. In this stressful time, it is important to ensure that the emotional needs of the family are met.

A useful resource is a grief packet that can be given to the parents following the demise. This usually includes referrals for counseling, support groups, and other resources. A container or folder can be included so that the family can preserve keepsakes such as photos, footprints, or a lock of hair. Spiritual support is an important resource during such difficult times and should always be offered to patients and their families.

Currently, which tests are most effective in evaluating a fetal demise have not been agreed upon. Therefore, authorities vary in their recommendations. Most of the testing recommendations in the past have been based on expert opinion rather than scientific studies. The Stillbirth Collaborative Research Network currently has ongoing studies, which will hopefully define the optimal diagnostic evaluation for this difficult clinical problem. 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. [28]  

An Obstetric Care Consensus regarding management of stillbirth was published jointly by the Society for Maternal Fetal Medicine and the American College of Obstetricians and Gynecologists. The following strong recommendations were made regarding evaluation of stillbirth [2] :

  • Inherited thrombophilias have not been associated with stillbirth, and testing for them as part of a stillbirth evaluation is not recommended
  • In women who decline invasive testing, a portion of the placenta, an umbilical cord segment, or internal fetal tissue can be sent for genetic analysis
  • Microarray analysis, incorporated into the stillbirth workup, improves the test success rate and the detection of genetic anomalies compared with conventional karyotyping.
  • Genetic evaluation for specific abnormalities should be guided by the clinical history and detected fetal abnormalities
  • Evaluation of a stillbirth should include fetal autopsy; gross and histologic examination of the placenta, umbilical cord, and membranes; and genetic evaluation.
  • Gross and microscopic examination of the placenta, umbilical cord, and fetal membranes by a trained pathologist is the single most useful aspect of the evaluation of stillbirth and is an essential component of the evaluation
  • The general examination of the stillborn fetus should be done promptly, noting any dysmorphic features and obtaining measurements of weight, length, and head circumference.
  • Fetal autopsy should be offered because it is one of the most useful diagnostic tests in determining the cause of death
  • Genetic analyses are of sufficient yield that they should be performed in all cases of stillbirth after appropriate parental permission is obtained.

Despite extensive evaluation, up to 60% of stillbirths have no identifiable etiology. Attempting to determine the cause of fetal death remains important because it may influence estimates of recurrence and future preconceptional counseling, pregnancy management, prenatal diagnostic procedures, and neonatal management. Many institutions use a selective workup based on clinical findings. For example, when clinical findings strongly suggest a cause for the fetal demise, either no further testing or limited testing is performed. Causes deemed fairly obvious include cord accident (ie, prolapse, entanglement, true knot, tight nuchal cord), anencephaly, or previously known lethal karyotype. In such cases, no further workup is necessary.

In most cases of stillbirth, the minimal workup should include fetal autopsy and placental pathology. Fetal autopsy provides important information in 30% of cases, whereas placental pathology provides additional information in another 30% of cases. [2] In the setting of fetal anomaly, genetic testing (karyotype, microarray) is also strongly recommended. If stillbirth occurs in the setting of preterm labor, chorioamnionitis, preterm prelabor rupture of membranes, or suspected infection, expanded testing may be of limited utility. When the stillbirth occurs in the setting of fetal growth restriction or hypertension, or in the absence of other clinical clues, evaluation should be expanded to include testing for fetal-maternal hemorrhage  (Kleihauer-Betke test or flow cytometry for fetal cells in maternal circulation), antiphospholipid antibodies (lupus anticoagulant, anticardiolipin antibodies, beta-2 glycoprotein antibodies), and genetic testing. In cases of placental abruption or when drug use is suspected, a toxicology screen is recommended.

The most important part of the workup of a fetal demise is the autopsy of the fetus. The yield is increased when dysmorphic features, inconsistent growth measurements, anomalies, hydrops, or growth restriction are present. The decision to proceed with an autopsy must be made by the parents, and informed consent is necessary. With parents who are resistant to the idea of a complete autopsy, a limited fetal evaluation should be discussed with the family. Although uncommon, postmortem magnetic resonance imaging (MRI) scans can provide valuable information in the evaluation of a fetus when an autopsy cannot be performed. Postmortem MRI using 1.5-Tesla magnets is the most studied technique and offers an overall diagnostic accuracy of 77-94%. [29]

The placenta and the membranes should be carefully examined, including cultures. An algorithm or checklist is helpful to avoid omissions (see image below). This inspection is even more important if the family declines an autopsy.

This is an example of a checklist to be used follo This is an example of a checklist to be used following fetal death. Courtesy of Santa Clara Valley Medical Center.

Specimens for cytogenetic analysis should be obtained using sterile techniques and instruments. Acceptable specimens include amniotic fluid obtained by amniocentesis at the time of diagnosis (preferred), a placental block (1 × 1 cm) taken from below the cord insertion site, umbilical cord segment (1.5 cm), or internal fetal tissue such as costochondral junction or patella (skin is not recommended). Specimens should be placed in sterile tissue culture medim of lactated Ringer's solution and kept at room temperature for transportation. Specimens should not be placed in formalin.

Fetal chromosome analysis should be considered in all cases. It is especially important if the fetus is dysmorphic, has growth restriction, is hydropic, or has anomalies or other signs of chromosomal abnormality. Chromosomal analysis should also be considered in patients with multiple pregnancy losses, especially with a history of second- and third-trimester losses or when a parent has a balanced translocation or mosaic chromosomal pattern. Options for testing include conventional karyotype or microarray analysis. Karyotype analysis is less costly compared to microarray, but the test failure rate is higher in the setting of fetal demise because it can only be performed if the cells are viable. Microarray is better suited for evaluation of fetal death because DNA can still be analyzed in macerated fetuses and nonviable tissue, where culturing and karyotyping has lower yield. [30]

The Stillbirth Collaborative Research Network conducted a population-based study of stillbirth and found that microarray yields results in 87.4% of cases compared with 70.5% for conventional karyotype. [31]  Microarray also detected more genetic abnormalities in stillbirth cases (8.3% vs 5.8%). Detection of abnormal copy variants by microarray is increased further in the setting of small for gestational age stillborn fetuses. Abnormal copy number variants not detectable by traditional karyotype make up approximately 50% of the genetic abnormalities in this population. [32]  Recently, whole genome sequencing has also been proposed in cases of unexplained stillbirth with normal microarray. One group employed whole genome sequencing and bioinformatic filtering techniques as a comprehensive, unbiased genetic investigation into 16 fetal, perinatal, and early infant deaths, and a likely genetic cause was identified in two cases and a speculative genetic cause in a further six cases. [33] Yet, further data are needed before implementing such testing on a larger scale, in light of cost considerations. 

A summary of the protocol for the fetus and placenta is as follows:

  • Careful inspection

  • Measure weight, head circumference, and length of fetus

  • Weight of placenta

  • Photographs of fetus and placenta

  • Placental cultures for suspected Listeria infection (to obtain placental cultures, separate the amnion and the chorion and submit a culture specimen using Stuart media)

  • Radiographs, if indicated

  • Autopsy

  • MRI, if no autopsy

  • Fetal karyotype, microarray

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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 reagin test

  • Thyroid function testing (ie, TSH, FT4)

  • Urine toxicology screening

The above tests have traditionally been a part of an evaluation for the etiology of fetal demise. If diabetes screening has been performed during the prenatal period, repeat testing for diabetes is probably not necessary unless the stillborn fetus is large for gestational age. Similarly, if the patient has no signs or symptoms of thyroid disease, thyroid dysfunction is unlikely to be the cause of the demise. However, these tests are inexpensive, and normal results may be reassuring to the patient.

Additional tests that should be considered are as follows:

  • Antibody screening

  • CBC count with platelet count

  • Kleihauer-Betke test or flow cytometry 

  • Laboratory tests for antiphospholipid syndrome: See Antiphospholipid Antibody Syndrome and Pregnancy.

  • Inherited thrombophilia panel in select cases 

    • Inherited thrombophilias have not been associated with stillbirth, and routine testing for them as part of a stillbirth evaluation is not recommended. [34]

    • A multicenter, prospective, observational cohort study concluded that there was no association between prothrombin G20210A mutation and pregnancy loss, preeclampsia, abruption, or SGA neonates in a low-risk population. [35] The current ACOG Practice Bulletin, Management of Stillbirth, does not recommend testing for inherited thrombophilias as part of a stillbirth evaluation. [2]  Similarly, in the ACOG Practice Bulletin, Inherited Thrombophilias in Pregnancy, there is no recommendation to screen for inherited thrombophilias with pregnancy loss. [36]

    • While some authorities recommend maternal testing in all cases of fetal demise, a more selective approach is to limit testing to patients who have a history of venous thrombosis, positive family history, severe placental pathology, severe preeclampsia in the second or early third trimester, abruption, or significant intrauterine growth retardation. The value of thrombophilia testing in any circumstance in obstetrics has recently been questioned. [37, 38]

  • Infection: See Bacterial Infections and Pregnancy. Infection is a cause of fetal demise. The frequency is higher in developing countries. Autopsy and histologic evaluation of the placenta is probably the best way to document an infectious etiology for a fetal demise.

Authority opinions vary as to which panel of tests is appropriate. Traditionally, most authorities have recommended obtaining TORCH (toxoplasmosis, rubella, cytomegalovirus, and herpes simplex virus) antibody titers. In reality, this is rarely helpful in the diagnosis. In addition, it is questionable whether cytomegalovirus virus causes fetal demise. If no obvious cause for the demise is established or if clinical signs or symptoms suggest infection, consider testing for (1) cytomegalovirus (acute and chronic titers), (2) rubella virus (acute and chronic titers, if not immune), (3) parvovirus (acute and chronic titers), and (4) Toxoplasmosis gondii (acute and chronic titers) and (5) syphilis. A more cost-effective approach is to limit testing for cytomegalovirus, rubella virus, and T gondii to those patients in whom clinical findings suggest the possibility of intrauterine infection (ie, those with intrauterine growth restriction, microcephaly).

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Testing for Fetal Demise

The following provides a summary of the current status of testing for fetal demise. This is adopted with permission from the work of Dr. Robert M. Silver and the Stillbirth Collaborative Research Network. This summary has been modified as more recent studies have become available.

Commonly accepted tests

Commonly accepted tests are as follows:

  • 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, for antiphospholipid testing

  • Anticardiolipin anticoagulant, for antiphospholipid testing

  • Anti-B 2 -glycoprotein 1 IgG or IgM antibodies

Useful in some circumstances

The following tests are useful in some circumstances:

  • Factor V Leiden

  • Prothrombin mutation

  • Protein C, protein S, and antithrombin III deficiency

  • TSH

  • Hemoglobin A1C

  • TORCH titers

  • Placental cultures

  • Testing for other thrombophilias

Developing technology

Developing technology includes the following:

  • Comparative genomic hybridization

  • Testing for single gene mutations

  • Testing for confined placental mosaicism

  • Nucleic acid-based testing for infection

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Management of Future Pregnancy

If a particular medical problem is identified in the mother, it should be addressed prior to conception. Interventions may include optimization of conditions such as diabetes, thyroid disease, hypertension, and lupus. For example, tight control of blood glucose prior to conception can substantially reduce the risk of congenital anomalies in the fetus. Efforts can be made to improve nutrition and exercise habits, with reduction in body mass index if necessary. Cessation of any ongoing substance use should be addressed, when appropriate. Preconceptional counseling is also helpful if congenital anomalies or genetic abnormalities are found. Genetic screening and detailed ultrasound can evaluate future pregnancies. In some cases, such as cord occlusion, the patient can be assured that recurrence is very unlikely.

The optimal interpregnancy interval after a stillbirth is uncertain. However, it is reasonable to advise patients to delay conception at least 6 to 12 months to achieve psychological closure. One study found that up to 6 months following a pregnancy loss, women showed greater depression, anxiety, and somatization than women who gave birth to living babies. Over time the mental health of women who had experienced a loss was found to improve and at 1 year was comparable to that of women who gave birth to living babies and to that of women in general. [39]  An additional consideration is that the optimal interpregnancy interval appears to be 18 to 24 months for most individuals. [40]

Fetal death of unknown cause is a special problem. Providers may offer more frequent prenatal visits and frequent testing, such as nonstress tests and ultrasound examinations, to reduce patient anxiety and stress.  While there is little evidence that intensive monitoring in future pregnancies will prevent stillbirth, women with previous unexplained stillbirth are at increased risk for recurrence, with a 3-4 fold increase reported in some studies. [41, 42]  Therefore, ACOG recommends antepartum testing starting at 32 weeks of gestation for women with prior stillbirth, or 1-2 weeks earlier than the previous stillbirth, in an otherwise healthy mother.  [2]  Sonographic screening for growth restriction after 28 weeks is also recommended. Weekly biophysical profile or fetal heart rate testing can be combined with maternal kick counts in the third trimester. Although many practitioners offer delivery before the estimated due date, expert consensus guidelines suggest avoiding scheduled delivery before 39+0 weeks if the previous stillbirth was unexplained and the current pregnancy is uncomplicated. [43]  However, patient care should be individualized if risk factors for adverse outcomes are present. Shared decision-making regarding timing of delivery is recommended in all cases, balancing maternal and fetal/neonatal considerations. 

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