1036 Familial aggregation of stillbirth

Abstract

Stillbirth occurs in 1 out of every 168 pregnancies and accounts for 60% of perinatal deaths in the U.S. Prior studies assessed mother-daughter inherited predisposition to stillbirth and miscarriage but found little to no evidence of risk transmission. We conducted a retrospective cohort study to determine the familial aggregation and high-risk extended pedigrees of stillbirth. We utilized the Utah Population Database (UPDB), a population-based genealogy linked with state fetal death record database to identify mothers who suffered stillbirth between 1978 and 2018. The pedigrees of related family members were determined to identify the first-degree (father, mother and full-siblings), second-degree (grandparents, aunts/uncles, and nieces/nephews) and third-degree (first cousins) relatives of the affected mothers (probands). High-risk pedigrees with excess clustering of stillbirth were identified using the Familial Standardized Incidence Ratio (FSIR), which compares the incidence of stillbirth in a family to its expected incidence in the UPDB population. Mothers with stillbirth (N=7756) and their first-, second-, and third-degree relatives (n=391,797) were identified (Table 1 and Table 2). High-risk pedigrees (n=197) with excess clustering of stillbirth (FSIR ≥ 2; P-value < 0.05; Observed stillbirths ≥ 10) were identified for mothers (probands; n=1764 [22.7%]). Table 1 shows the top 10 high-risk pedigrees with statistically significant evidence for familial aggregation of stillbirth. Stillbirth persisted among 2nd degree relatives (0.34%) and 3rd degree relatives (0.38%) (Table 2). Familial aggregation of stillbirth occurs and is present in 22.7% of women with stillbirth. Stillbirth persisted in more distant relatives, which may further support a heritable or genetic contribution, as environmental exposures in distant relatives are expected to be randomly distributed compared with a proband’s exposures. Future studies should examine genetic variants in these high-risk families to identify de novo and inherited genes associated with stillbirth.View Large Image Figure ViewerDownload Hi-res image Download (PPT)