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.