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.
