Familial risk of placental abruption

Placental abruption (PA), the partial or complete separation of the placenta before delivery, occurs in 1-2 % of pregnancies and is associated with severe maternal and perinatal morbidity and mortality. The etiology of PA is complex, and the increased recurrence risk in subsequent pregnancies suggests a potential genetic contribution. Investigating PA in large families may reveal important insights into inherited risk and the extent to which genetic factors contribute to PA. To guide future gene-discovery studies, we investigated the familial risk of PA using data from 1.2 million pregnancies across multi-generational families in the Utah Population Database.

To estimate familial risk of PA using a large population database.

We conducted a population-based matched case-control study to examine familial risk of PA. PA cases (n = 32,823) and controls (n = 98,387) were ascertained using maternal death (1904-2020), fetal death (1904-2020) and fetal birth (1939-2020) certificates, and inpatient medical records (1996-2020) from the University of Utah Health Sciences Center. Three controls were matched to each case on maternal age, parity and number of relatives that were available in the database. PA risk for first-degree relatives (FDR), second-degree relatives (SDR), and third-degree relatives (TDR) of family members were estimated comparing cases and controls using generalized linear mixed-effect and conditional logistic regression models. Risk estimates were adjusted for the matching variables, year of pregnancy, maternal race/ethnicity and education level.

Of 1,168,378 pregnancies analyzed in the Utah Population Database, 32,823 PA cases and controls (n = 98,387) were identified. FDRs, SDRs and TDRs had a 1.18-fold (95 % CI: 1.12-1.23), 1.09-fold (95 % CI: 1.06-1.13), and 1.01-fold (95 % CI: 0.99-1.03) increased PA risk when a family member experienced any PA, respectively. When family members experienced only one PA, FDRs, SDRs and TDRs had a 1.17-fold (95 % CI: 1.11-1.22), 1.09-fold (95 % CI: 1.05-1.13) and 1.01-fold (95 % CI: 0.98-1.03) increased PA risk, respectively. When family members experienced two or more PA, FDRs, SDRs and TDRs had a 1.38-fold (95 % CI: 1.17-1.64), 1.14-fold (95 % CI: 1.00-1.29) and 1.13-fold (95 % CI: 1.05-1.22) increased PA risk, respectively.

We observed familial risk of PA even among distantly related individuals, extending beyond first-degree relationship, suggesting inherited risk factors contribute to PA. Genomic investigations in multi-generational families with PA, which provide more statistical power for gene discovery, may help identify pathogenic heritable mechanisms, leading to discovery of biomarkers and therapeutics to prevent PA.