A New System for Determining the Causes of Stillbirth

Abstract

OBJECTIVE To describe the methods for assigning the cause of death for stillbirths enrolled in the Stillbirth Collaborative Research Network (SCRN). METHODS A complete evaluation, including postmortem examination, placental pathology, medical record abstraction, and maternal interview was available on 512 stillbirths among 500 women. These 512 stillbirths were evaluated for cause of death using the definitions outlined in this report. Using the best available evidence, SCRN investigators developed a new methodology to assign the cause of death of stillbirths using clinical, postmortem, and placental pathology data. This new tool, designated the Initial Causes of Fetal Death, incorporates known causes of death and assigns them as possible or probable based on strict diagnostic criteria, derived from published references and pathophysiologic sequences that lead to stillbirth. RESULTS Six broad categories of causes of death are accounted for, including maternal medical conditions; obstetric complications; maternal or fetal hematologic conditions; fetal genetic, structural, and karyotypic abnormalities; placental infection, fetal infection, or both; and placental pathologic findings. Isolated histologic chorioamnionitis and small for gestational age were not considered causes of death. CONCLUSION A new system, Initial Causes of Fetal Death, to assign cause of death in stillbirths was developed by the SCRN investigators for use in this study but has broader applicability. Initial Causes of Fetal Death is a standardized method to assign probable and possible causes of death of stillbirths based on information routinely collected during prenatal care and the clinical evaluation of fetal death.

Genome-Wide Array-Based Copy Number Profiling in Human Placentas From Unexplained Stillbirths

“…FISH can detect smaller-size abnormalities in the range of 50-150 Kb, but it is limited by the small number of probes (maximum ~5) that can be tested simultaneously requiring an informed selection of the specific probes to be used. Using these methods, cytogenetic abnormalities have been described in a small percentage (5-13%) of all stillbirths (13,17,18). Thus, array based approaches to identifying genomic abnormalities in stillbirths might be expected to have two main advantages over cytogenetic methods.…”

“…Accurate determination of the relative contribution of these and other factors, such as environmental exposures, to stillbirth is hampered by inaccurate fetal death records (11,12) and incomplete evaluation of such potential comorbidities. As such, the cause of as great as 60% of stillbirths remains classified as "unknown" (13)(14)(15)(16). The poorly understood epidemiology of stillbirths recently prompted the National Institute of Health to identify it as a high priority research focus, resulting in the Stillbirth Collaborative Research Network (13,14).…”

“…As such, the cause of as great as 60% of stillbirths remains classified as "unknown" (13)(14)(15)(16). The poorly understood epidemiology of stillbirths recently prompted the National Institute of Health to identify it as a high priority research focus, resulting in the Stillbirth Collaborative Research Network (13,14). Because the empiric recurrence risk of stillbirth approximates 3-5% (10), identification of the etiology in index cases is essential to better stratify recurrence estimates, potentially reduce parental anxiety, and diminish future unnecessary and expensive antenatal testing in subsequent pregnancies (10,4).…”

Placental Pathology and Stillbirth: A Review of the Literature and Guidelines for the Less Experienced

“…However, in some cultures postmortem examination may be refused for cultural or religious reasons or simply be too expensive. This refusal is in part confounded by the findings in a number of studies which show that even after a detailed postmortem, the cause of death may remain unknown in 57.9 to [70% though the number where cause of death is identified may rise to [90% when the placenta is examined in detail [5,[45][46][47]. Indeed, examination of the placenta alone may help to define causation and indicate treatment options in subsequent pregnancies.…”

The Pediatric Autopsy in Africa

“…In addition, the subcapsular adrenal cortex often assumes a pseudoacinar configuration with small hemorrhages in CEREBRAL HYPOXIA AND ISCHEMIA Cerebral hypoxia and ischemia have a significant role in explaining the mechanism of death in the very young. This is often because of the prevalence of various forms of placental pathologic processes, 21 frequent respiratory infections, and congestive cardiac failure at this time of life. As a consequence of ischemia or hypoxia, hemorrhages most often occur in the germinal matrix of the ventricles (Figure 7, A), cerebellum, and around small blood vessels (ring hemorrhages).…”