Methodologic Issues in the Design and Analysis of Epidemiologic Studies of Pregnancy Outcome

Using epidemiology to elucidate the causes of adverse pregnancy outcomes offers unique opportunities and poses distinctive challenges. The context of pregnancy includes contraception and planning, medical interventions altering the natural history, and the tendency for selective participation in demanding research protocols. Several key pervasive issues are considered in detail: 1) the close temporal proximity of determinants and outcomes, which makes separation of causes and effects difficult and introduces the real possibility of reverse causality; 2) non-random allocation of exposure, often done consciously in response to concerns about having a healthy pregnancy or to the health of the pregnancy itself, making confounding a major concern; 3) heterogeneity of pregnancy outcomes, with endpoints such as pregnancy loss and preterm birth arising through diverse pathways that are not easily identified and if grouped, could diminish the magnitude of observed associations; and 4) racial and ethnic disparities, which pose a public health challenge in the USA and offer a potentially important opportunity for identifying preventable causes of adverse pregnancy outcome. Sophisticated biological and statistical methods are needed to advance epidemiologic research in this area.