Placental Abruption, Preterm Delivery, and Cardiovascular Disease in Twin Offspring.

BACKGROUND: In utero exposures to certain pathologies during pregnancy increase offspring cardiovascular disease (CVD) risks, and pregnancy complications and CVD risks are higher in twins than in singletons. However, the association between placental abruption and nonfatal incident CVD in twin offspring, and whether the abruption effects are mediated through preterm delivery, is unknown. METHODS: We used the PACER (Placental Abruption and Cardiovascular Event Risk) offspring cohort, which links births to hospitalizations and mortality records in New Jersey from 1993 to 2020 (28 years of follow-up) and is restricted to twin offspring. In a Cox model, we estimated the counterfactual decomposition of the abruption-CVD association into a natural direct and indirect effect through preterm delivery. RESULTS: Of 116 796 twin births, 2597 (2.2%) were complicated by abruption. The rate of incident CVD was higher among abruption than nonabruption births (1560 versus 577 per 100 000 person-years). Abruption was associated with a 2.47-fold increased risk of CVD in the twin offspring, with similar risks for heart disease and stroke. Results indicated that 40% of the total effect was mediated through preterm delivery <37 weeks; the proportion mediated increased with earlier gestational ages at delivery. These risks persisted after accounting for unmeasured confounding bias. CONCLUSIONS: Placental abruption is associated with higher CVD risk in twins through early adulthood, with substantial mediation of effects through preterm delivery. Efforts to optimize obstetric care for pregnant women carrying twins to reduce the risk of abruption may be worthy of consideration. This may translate to public health benefits in reducing CVD in twin offspring.