Introduction:
Placental abruption (PA) – the partial or complete separation of the placenta before delivery – occurs in approximately 1-2% of all pregnancies and is associated with considerable maternal and perinatal morbidity and mortality. 1–3 While the pathophysiology is uncertain, the leading theory involves acute vasospasm or thrombosis in small blood vessels at the placental-uterine interface which leads to hemorrhage. 4 Significant abruptions can cause maternal hemodynamic instability, coagulopathies, and often require surgical management to facilitate delivery. For the fetus or neonate, abruptions carry a 9-fold increase risk of stillbirth and are highly associated with perinatal morbidity and mortality, particularly in the setting of preterm delivery. 3 PA is also associated with fetal growth restriction and hypoxic brain injury, which can lead to long-term pediatric health consequences.5,6 PA is a clinical diagnosis that is difficult to predict, and in the majority of cases, impossible to prevent. Although epidemiologic studies have identified risk factors for PA, such as pre-labor rupture of membranes (PROM), smoking, prior PA, hypertension, and a history of cesarean delivery, the majority of cases occur in the absence of risk factors. 1,7
Investigation for a genetic contribution underlying PA began after practitioners noticed a significant recurrence risk for individuals in subsequent pregnancies as well as a perceived familial heritability in pedigrees. 8,9 Initial population-based studies determined the recurrence risk of PA to be 6-10 times higher for the same individual and the odds of PA among first degree relatives to be 2-4 times higher than the baseline risk. 10,11Candidate genetic loci related to trophoblast-like cellular invasion, mitochondrial biosynthesis, angiogenesis, oxidative stress, and circadian rhythm have been identified through genome-wide association studies and candidate gene association studies. 12–16An important step towards the discovery of preventative strategies or therapeutic targets is the accurate estimation of a person’s inherited PA risk as opposed to the environmental contribution to this disease process. This study aims to estimate the familial risk of placental abruption using a large, well-characterized population database.