PROJECT SUMMARY/ABSTRACT Cardiovascular disease (CVD) is the leading cause of death in the US, with the prevalence projected to keep rising. The origins of CVD begin early in life, including child obesity and atherosclerotic plaque formation, which predict later CVD. To address the origins of CVD, the American Heart Association created 2020 Impact Goals emphasizing promotion of cardiovascular health early in life, which includes measures of both physical risk factors (e.g., body mass index [BMI], blood pressure) and health behavior (e.g., diet). Stress in the prenatal period is hypothesized to contribute to CVD in adulthood. However, little is known about plausible biological mechanisms. The focus of this proposal is to assess the role of placental corticotrophin-releasing hormone (CRH), an understudied stress responsive hormone that regulates fetal development and birth outcomes, in offspring CVD risk (BMI z-score, waist circumference, and blood pressure) and obesogenic eating behaviors. This project will utilize a longitudinal design to prospectively follow a sample of mother-child dyads (n = 150). Placental CRH was assessed as a part of a NIMH-funded study (R01MH109662) through maternal blood samples at three timepoints during pregnancy (10, 24, and 34 gestational weeks). Child CVD risk (BMI z-score, waist circumference, and blood pressure) and obesogenic eating behaviors are being assessed as a part of a follow-up NHLBI-funded study (R01HL155744) at a laboratory visit when the children are 3-years-old. The current project has two aims: Aim 1: To test the hypothesis that rapid increases in placental CRH across gestation predict greater offspring CVD risk at three years of age; and Aim 2: To test the hypothesis that increased placental CRH production across gestation predicts greater offspring obesogenic eating behaviors. Identifying the associations between placental CRH across gestation and both offspring CVD risk and obesogenic eating behaviors will elucidate early origins of cardiovascular health and provide targets for early prevention and intervention. While conducting the proposed study, the applicant will gain essential training at the University of Denver that strongly supports her goal of becoming an independent NIH-funded researcher. The applicant’s goals include 1) increasing understanding of the prenatal period as a sensitive period, focusing on prenatal stress physiology (e.g., placental CRH); 2) developing expertise in the assessment of CVD risk during early childhood; 3) developing expertise in the assessment of eating behaviors during early childhood; 4) learning advanced statistical modeling of longitudinal data; and 5) developing grant writing skills. The completion of these training objectives, along with the strong mentorship from the project sponsor (Elysia Davis, PhD) and co- mentors (Jenalee Doom, PhD, Deborah Glueck, PhD, Julie Lumeng, MD, and Benjamin Hankin, PhD), will support this applicant’s career trajectory toward becoming an independent researcher.

PROJECT NARRATIVE Cardiovascular disease (CVD) is the leading cause of death in the US and the origins of CVD begin early in life, however, the mechanisms by which early experiences influence CVD risk are poorly understood. This project examines whether the stress responsive hormone placental corticotrophin-releasing hormone is associated with offspring CVD risk and obesogenic eating behaviors in early childhood. Consistent with NHLBI and American Heart Association goals, these findings could elucidate a potential mechanism by which prenatal factors influence cardiovascular health and provide targets for early childhood prevention of later CVD.