DESCRIPTION (provided by applicant): This project seeks to evaluate a model of childhood obesity that begins with maternal pre-pregnancy obesity as a distal risk factor contributing to the development of appetite dysregulation and poor executive functioning, increasing a child's risk for excess weight gain. The study will take advantage of a perinatal birth cohort with over 2000 births that has obtained prospectively collected data from the first trimester through infancy, inclusive of pre-pregnancy weight at the first prenatal visit, gestational weight gain, surveys regarding nutrition, stress and lifestyle behaviors, data from medical records on pregnancy and birth complications, maternal blood at the first trimester, and umbilical cord blood at delivery. The proposed study will recruit mother/child dyads from this cohort and conduct detailed assessments of IQ, executive functions (attention, inhibitory control, memory, affective-based decision making), appetite regulation using the eating in the absence of hunger laboratory paradigm, dietary intake, and anthropometric growth among 400 children at ages 4 years and two- years later at 6 years. Maternal blood specimens collected during the first trimester and cord blood at birth will be used to assay Interleuken-6 (IL-6) and monocyte chemoattractant protein 1 (MCP-1), two cytokines important in both metabolism and normal brain development. The primary hypothesis is that maternal obesity influences neurodevelopmental processes that regulate appetite and executive functions resulting in increased risk for obesity in offspring. A secondary/exploratory hypothesis is that markers of prenatal neuro-inflammatory processes mediate the effect of maternal obesity on adverse child outcomes. Conducting this study in the context of an established perinatal birth cohort provides a cost-effective opportunity to achieve our aims. The study will aid in disentangling the associations between maternal pre-pregnancy obesity, childhood appetite regulation, executive functions and child weight gain. By understanding how developmental factors shape individual differences that predict child obesity, it is possible to markedly improve prevention interventions by targeting key risk factors for childhood obesity at earlier developmental periods and create tailored prevention programs that shift children's weight trajectory toward more healthy outcomes.

PUBLIC HEALTH RELEVANCE: Nearly 1 in 5 women are obese when they start their pregnancy. To date, we know little about what impact pre- pregnancy obesity has on children's brain development and his/her risk for obesity. We will evaluate the extent to which pre-pregnancy obesity and gestational weight gain affect children's eating and capacity to exercise good self-control, and how these factors might be related to child weight gain. The knowledge gained will improve our understanding of why some children are more vulnerable to obesity and point to ways we might be able to develop more effective prevention strategies.