Impact of Antenatal Depression, Anxiety, and Stress on Fetal

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Project 1 will focus on the fetal and obstetrical consequences of maternal stress, depression, and anxiety during pregnancy. Information that better informs the clinical decision potentially affects >400,000 women in the United States annually. The treatment of maternal depression and anxiety during pregnancy continues to stimulate vigorous debate with the emphasis on the reproductive safety of antidepressant medications. Recently, there have been reports of purported "antidepressant neonatal withdrawal", and a renewed attention with respect to potential teratogenic effects (e.g. ventral septal defects). Unfortunately, the potential impact of maternal stress, depression, and anxiety on the fetus and obstetrical outcome is seldom included in these reports. The extant literature on the impact of maternal mental illness typically uses single point assessments (predominantly in mid to late pregnancy) of maternal depression and anxiety. While such studies have demonstrated alterations in fetal activity, fetal heart rate, and an increase in obstetrical complications (low birth weight, preterm labor, preterm delivery), they have only speculated about the mechanisms based on cross sectional assessment. Similarly, these investigations have failed to account for other exposures that may influence outcome (medications, tobacco, etc). Project 1 will fill these gaps utilizing the well characterized women from Core B. We will determine the impact of maternal depression and anxiety, in any, on biological indices of stress (both acute and cumulative) and the relationship of these measures and maternal symptoms with uterine blood flow, fetal activity, fetal heart rate, obstetrical outcome, neonatal outcome. The center design permits blinded assessments of these relationships - an incremental advance over previous investigations. The focus on a clinical population will provide a cohort of pregnant women with antidepressant exposure. The modulatory effects, if any, of antidepressants on our outcome variables are unknown. Blinded assessment of obstetrical and neonatal outcome will directly address many of the concerns recently reported. The potential impact of exposure (e.g. ng/ml in cord blood) will be included in data analysis. The novel data generated from Project 1 will serve as candidate phenotypes for Project 2, and additional potential moderators of infant outcome in Project 3.