Population-Based Investigations to Study the Association of Cardiovascular Polymorphisms and Adverse Pregnancy Outcome

Adverse pregnancy outcome refers to placenta-mediated complications that may share a common etiopathogenesis in some cases. Unraveling associations between prothrombotic genetic predispositions and these pregnancy disorders, namely recurrent fetal loss, stillbirth, severe preeclampsia, intrauterine growth restriction, and placental abruption, requires rigorous epidemiological studies involving large cohorts of patients with sufficient numbers of the adverse pregnancy outcomes in question. Such is the case with the Denmark National Birth Cohort, which was initiated in 1996 and followed pregnant women giving birth from the years 1996 to 2002. In addition, national registers exist which can be linked together. Two studies have been initiated. One is a retrospective cohort study concerning primiparous women, with singleton pregnancy and with no identifiable congenital malformation. The purpose of this study is to determine the long-term cardiovascular risk of women whose pregnancies were complicated by adverse pregnancy outcome. Preliminary evidence suggests that the presence of an adverse pregnancy outcome augments the cardiovascular disease risk by an odds ratio of 1.21 (P < 0.001). The second study focuses on pro-thrombotic and cardiovascular genetic polymorphisms in a nested-case control study comparing pregnancies with and without an adverse pregnancy outcome in the index pregnancy. This study will be adequately powered to determine the relationship between adverse pregnancy outcome and pro-thrombotic and cardiovascular genetic polymorphisms. These studies are urgently needed to accurately assess the linkage between family history, presence of adverse pregnancy outcome, and long-term cardiovascular risk.

Keywords: thrombophilia, adverse pregnancy outcome, cardiovascular disease, genetic polymorphisms, prospective cohort