Objective: This study aims to estimate the familial risk of placental abruption using a large population database. Design: Retrospective familial aggregation study of placental abruption utilizing a case-control design. Population: The Utah Population Database is a genealogic database of over 11 million individuals, which contains medical and demographic information linked to official records dating back to the 1900s. Methods: Cases of placental abruption and controls were ascertained from birth certificates, death certificates, and inpatient medical records. Controls were matched 3:1 to cases based on age, parity, and number of relatives in the database. Familial risk of placental abruption was estimated using generalized linear mixed-effect regression and conditional logistic regression. Main outcome measures: Unadjusted and adjusted odds of placental abruption between first-, second-, and third-degree relatives. Results: Of 1,168,378 pregnancies analyzed in the Utah Population Database, 32,823 cases (2.8%) of placental abruption were identified. First-degree relatives inherit an adjusted odds of placental abruption estimated at 1.18 (95% CI: 1.12 – 1.23) when a family member has had at least one placental abruption, and 1.38 (95% CI: 1.17 – 1.63) with two or more placental abruptions. The estimated effect is lower for second- and third-degree relatives. After controlling for clinical risk factors, individuals inherit an adjusted odds of placental abruption estimated at 1.16 (95% CI: 1.03 – 1.31, p=0.014) with a first-degree family history of placental abruption. The estimates for second- and third-degree relatives using this method are not statistically significant. Conclusion: These findings represent an argument for the inheritance of genetic factors which predispose the occurrence of placental abruption.

Objective To determine if stillbirth aggregates in families and quantify its familial risk using extended pedigrees. Design State-wide matched case-control study. Setting Utah, United States. Population Stillbirth cases (n=9 404) and live-birth controls (18 808) between 1978 and 2019. Methods Using the Utah Population Database, a population‐based genealogical resource linked with state fetal death and birth records, we identified high-risk pedigrees with excess familial aggregation of stillbirth using the Familial Standardized Incidence Ratio (FSIR). Stillbirth odds ratio (OR) for first-degree relatives (FDR), second-degree relatives (SDR), and third-degree relatives (TDR) of parents with a stillbirth and live-birth were estimated using logistic regression models. Results We identified 390 high-risk pedigrees with evidence for excess familial aggregation (FSIR≥2.00 and P-value<0.05). FDRs, SDRs and TDRs of affected parents had 1.14-fold (95% confidence interval [CI]: 1.04-1.26), 1.22-fold (95% CI: 1.11-1.33), and 1.15-fold (95% CI: 1.08-1.21) higher stillbirth odds compared to FDRs, SDRs and TDRs of unaffected parents, respectively. Parental sex-specific analyses showed male FDRs, SDRs and TDRs of affected fathers had 1.22-fold (95% CI: 1.02-1.47), 1.38-fold (95% CI: 1.17-1.62), 1.17-fold (95% CI: 1.05-1.30) higher stillbirth odds compared to those of unaffected fathers, respectively. FDRs, SDRs and TDRs of affected mothers had 1.12-fold (95% CI: 0.98-1.28), 1.09-fold (95% CI: 0.96-1.24), and 1.15-fold (95% CI: 1.06-1.24) higher stillbirth odds compared with those of unaffected mothers, respectively. Conclusions We provide evidence for familial aggregation of stillbirth. Our findings warrant investigation into genes associated with stillbirth and underscore the need to design large-scale studies to determine its genetic architecture.