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Determining the cause of fetal death aids maternal coping, helps assuage any perceived guilt, permits more accurate counseling regarding recurrence risk, and may prompt therapy or intervention to prevent a similar outcome in subsequent pregnancies (American College of Obstetricians and Gynecologists, 2016a). Identification of inherited syndromes also provides useful information for other family members.
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Important tests in stillbirth evaluation are neonatal autopsy, chromosomal analysis, and examination of the placenta, cord, and chorioamnionic membranes (Pinar, 2014). Page and coworkers (2017) found placental pathology and fetal autopsy to be the most useful. One algorithm from the American College of Obstetricians and Gynecologists (2016a) is shown in Figure 35-4. Findings are documented in the medical record, and relevant prenatal events are delineated. Photographs are taken whenever possible, and a full radiograph of the fetus—a fetogram—may be performed. Postnatal magnetic resonance (MR) imaging or sonography may be especially important in providing anatomical information if parents decline a full autopsy (McPherson, 2017; Shruthi, 2017).
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Laboratory Evaluation
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If autopsy and chromosomal studies are performed, up to 35 percent of stillborn fetuses are discovered to have major structural anomalies (Faye-Petersen, 1999). Approximately 20 percent have dysmorphic features or skeletal anomalies, and 8 percent have chromosomal abnormalities (Pauli, 1994; Saller, 1995). In the absence of anatomic dysmorphology, up to 5 percent of stillborn fetuses will have a chromosomal abnormality (Korteweg, 2008). Although the American College of Obstetricians and Gynecologists (2016a) previously recommended karyotyping all stillborn fetuses, technological advancements of high-resolution, whole-genome sequencing—such as with chromosomal microarray analysis (CMA)—are now replacing standard karyotyping for chromosomal analysis of stillborn fetuses (Chap. 13, Chromosomal Microarray Analysis). CMA does not require dividing cells and is reported to be more useful in the evaluation of fetal death. This is especially true because the culturing of macerated fetal tissue is frequently unsuccessful (Reddy, 2012). Both the American College of Obstetricians and Gynecologists (2016c) and the Society for Maternal-Fetal Medicine (2016) now endorse the use of CMA for stillborn fetuses.
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Appropriate consent must be obtained to take fetal samples, including tissue or fluid obtained postmortem by needle aspiration. As recently outlined by the American College of Obstetricians and Gynecologists (2016c), any type of fetal or placental tissue or amnionic fluid can be submitted for genetic testing by CMA. Contamination with maternal tissue or blood is ideally avoided. If fetal blood cannot be obtained from the umbilical cord or by cardiac puncture, the American College of Obstetricians and Gynecologists (2016a) recommends at least one of the following samples: (1) a placental block measuring about 1 × 1 cm taken below the cord insertion site in the unfixed specimen; (2) umbilical cord segment approximately 1.5 cm long; or (3) internal fetal tissue specimen such as costochondral junction or patella. Tissue is washed with sterile saline before being placed in lactated Ringer solution or sterile cytogenetic medium. Notably, placement in formalin or alcohol kills viable cells. If conventional karyotyping is the only test available and the timing of death is recent, amnionic fluid can be obtained by amniocentesis, as those cells obtained in a sterile fashion provide a greater likelihood of cell growth and eventual result compared with tissue obtained after delivery. Maternal blood is obtained for Kleihauer-Betke staining; for antiphospholipid antibody and lupus anticoagulant testing if indicated; and for serum glucose measurement to exclude overt diabetes (Silver, 2013).
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In cases with significant growth restriction, with a family or personal history of thrombosis, or with severe placental pathology, testing for factor V Leiden mutation, prothrombin mutation, antithrombin level, and protein C and S activity may provide some information that could affect future pregnancy management (American College of Obstetricians and Gynecologists, 2016a). Our interpretation of relevant placental pathology includes derangements that stem from maternal vessel obstruction, which are described in Chapter 6. Although some have recommended routine evaluation of heritable thrombophilias, no evidence supports the clinical or financial efficiency of screening in an unselected population. Silver and colleagues (2016), with data from the Stillbirth Collaborative Research Network, found that most maternal and fetal thrombophilias were not associated with stillbirth and recommended against routine testing.
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Parents are offered and encouraged to allow a full autopsy. That said, valuable information can still be obtained from limited studies. Pinar and coworkers (2012) described the autopsy protocol used by the Stillbirth Collaborative Research Network. As an alternative, gross external examination combined with photography, radiography, MR imaging, bacterial cultures, and selective use of chromosomal and histopathological studies often aids determination.
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A complete autopsy is more likely to yield valuable data. An analysis of 400 consecutive fetal deaths in Wales showed that autopsy altered the presumed cause of death in 13 percent and provided new information in another 26 percent (Cartlidge, 1995). Other investigators have found that autopsy results changed the recurrence risk estimates and parental counseling in 25 to 50 percent of cases (Faye-Petersen, 1999; Silver, 2007). For example, Miller and associates (2016) recently demonstrated that placental examination with autopsy altered future medical management in 45 percent of cases.
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According to the survey by Goldenberg and coworkers (2013), most hospitals do not audit stillbirths. In other centers, however, maternal records and autopsy findings are reviewed on a monthly basis by a stillbirth committee composed of obstetricians, maternal-fetal medicine specialists, neonatologists, clinical geneticists, and perinatal pathologists. If possible, the cause of death is assigned based on available evidence. Most importantly, parents are then contacted and offered counseling regarding the reason for the death, the potential recurrence risk, and possible strategies to avoid recurrence.