Influences of Prenatal Phthalate Exposure on Early Childhood Overweight/Obesity and Potentially Protective Dietary Strategies - PROJECT ABSTRACT/SUMMARY Despite decades of traditional interventions targeting diet and physical activity, childhood obesity remains a pervasive and intractable public health problem. It is therefore imperative to prioritize discovery of novel, modifiable risk factors to prevent obesity beginning in early life. Environmental exposures during critical developmental windows, especially the prenatal period, may contribute to obesity development by altering infant physiology and metabolism. Among these potential environmental obesogens, phthalates are one class of endocrine-disrupting chemicals with ubiquitous exposure in the population. Phthalates may promote obesity through mechanisms involving oxidative stress, alteration of adipocyte formation and function, and interference with metabolic pathways. Prenatal exposure to phthalates has been associated with greater childhood body mass index (BMI) in some studies, but others have reported null or inverse associations. Importantly, methodological limitations, small sample sizes, and homogenous study populations of these prior investigations make it difficult to reconcile apparent discrepancies, limit our capacity to determine the most potent metabolites, and preclude identification of critical windows of vulnerability. Furthermore, no strategies have been identified to mitigate potential obesogenic effects of prenatal phthalate exposure. Oxidative stress and associated inflammation are proposed pathways linking phthalates to obesity. Therefore, dietary patterns that reduce oxidative stress, such as those rich in antioxidants and omega-3 fatty acids, may be an impactful intervention target during pregnancy. The proposed research will utilize the rich longitudinal data from the Environmental influences on Child Health Outcomes (ECHO) Program, a consortium of 69 pediatric cohorts from across the United States. The proposed project aims to examine the association between prenatal phthalate exposure and BMI z-score and overweight/obesity risk in children 2-5 years of age (Aim 1a) and explore prenatal critical windows of phthalate exposure on childhood BMI z-score (Aim 1b). As a solution- oriented approach, we will also evaluate how diets closely matching the Dietary Guidelines for Americans (Aim 2a) and those rich in fish consumption (Aim 2b) may modify the association of prenatal phthalate exposure with early childhood overweight/obesity. Our team's combined expertise extends across multiple domains critical to the success of this project. Dissertation committee members serving as key personnel bring substantial expertise in statistical methods, ECHO structure and organization, nutrition, childhood growth, and the effects of phthalate exposure on childhood health. Successful completion of this research will help set the stage for the development of strategies to mitigate the potential obesogenic effects of phthalate exposure in vulnerable populations. Given that childhood obesity tracks into adulthood, utilizing ECHO to address these aims will enhance the health of children for generations to come.
