Project Summary Exposure to high levels of stress during pregnancy can impact offspring cognitive, behavioral, and physical development. This is thought to reflect the effects of maternal stress hormones, which can cross the placenta and disrupt fetal development. Prenatal stress exposure might represent one of the mediating mechanisms in the Developmental Origins of Health and Disease, which suggests that the early environment holds lifelong implications for adult health. Prenatal stress exposure has been associated with poor birth outcomes, which increases risk for later chronic diseases. Animal and some human studies also suggest that prenatal stress exposure is associated with later cardiometabolic diseases such as insulin resistance and obesity independently of size at birth, perhaps reflecting effects of stress hormones on the developing HPA (hypothalamic pituitary adrenal) axis, which is involved in metabolism. However, human studies of prenatal stress are difficult to design, and we have limited data about physical and metabolic outcomes of prenatal stress in childhood and adolescence that might precede the development of adult disease. My Objective is to examine the effects of prenatal stress exposure on physical growth and metabolic patterns among 120 adolescents whose mothers were exposed to stress during pregnancy due to a severe ice storm in 1998; and among 262 toddlers whose mothers were pregnant during a flood in 2008. These children are already participating in regular assessments for two prospective longitudinal studies of prenatal stress exposure: Project Ice Storm and the Iowa Flood Study. The studies include measurements of size at birth and some anthropometric measurements in childhood; detailed assessments of maternal stress exposure; and data on potential confounding variables such as socioeconomic status, maternal trait anxiety, and other stressful life events occurring during pregnancy. The children in both studies participate in regular assessments during which I can collect additional data. Methods: I will analyze the effects of prenatal stress exposure on birth outcomes (birth weight, stature, and head circumference for gestational age) in both cohorts using already available data. I will collect detailed anthropometric measurements (height; weight; waist, hip, mid-upper-arm, and calf circumference; and triceps, subscapular, and suprailiac skinfolds) among Iowa Flood Study participants at age 21/2, and Project Ice Storm participants at age 131/2. Controlling for confounding variables, I will examine relationships between level of stress exposure and body size, lean muscle and fat mass, and fat distribution patterns. I will also use longitudinal measures of height and weight collected in Project Ice Storm to analyze if and how prenatal stress exposure impacts growth trajectories from birth to adolescence. Finally, I will measure fasting glucose and insulin levels for Project Ice Storm participants and analyze their relationship to prenatal stress levels. These unique data can help address unanswered questions about the developmental origins of health and disease, and will highlight many areas for future research.