PROJECT SUMMARY Women with severe obesity have high risks of adverse birth and child outcomes, including childhood obesity. There is a profound need to reduce risks among women who enter pregnancy with severe obesity as part of prenatal care, but there is scant evidence on appropriate Gestational Weight Gain (GWG) goals in women with severe obesity. Moreover, severe pre-pregnancy maternal obesity, adverse birth outcomes, and child obesity are most prevalent in low-income and racial/ethnic minority groups, who are vastly under-represented in obstetric and pediatric obesity research. The proposed research addresses the critical problem that GWG guidelines are likely too high for women with severe obesity, placing children at high risk for obesity and exacerbating disparities in childhood obesity. The overall objective of this study is to determine overall and trimester-specific GWG associated with the lowest risk of adverse birth and longer-term outcomes in children of mothers with severe pre-pregnancy obesity. This study leverages the ADVANCE Early Life Cohort, a unique cohort of low-income, racially and ethnically diverse mothers and children, constructed from electronic health record (EHR) data from U.S. community health centers. In contrast with most other EHR-based studies, this study population includes predominately publicly insured and uninsured patients. The proposed research will examine >37,000 mothers in ADVANCE living in 3 states (OR, CA, MA), and their children to conduct 3 specific aims. Aim 1: Determine overall and trimester-specific GWG associated with the lowest risk of adverse birth outcomes (small or large for gestational age, preterm birth, birth weight) in children of mothers with severe pre-pregnancy obesity. Hypothesis: Among children of mothers with severe pre- pregnancy obesity, birth outcomes are optimized when total and trimester-specific GWG are below current recommendations. Aim 2: Determine overall and trimester-specific GWG associated with the lowest risk of longer-term obesity-related outcomes (infant growth, BMI at 5 years of age) in children of mothers with severe pre-pregnancy obesity. Hypothesis: Among children of mothers with severe pre-pregnancy obesity, early indicators in child obesity risk are reduced with total and trimester-specific GWG below current recommendations. Aim 3: Determine the extent to which overall and trimester-specific GWG mediate the relationship between race/ethnicity and BMI at 5 years of age. Hypothesis: A substantial share (>10%) of previously observed racial/ethnic disparities in childhood obesity is attributable to GWG, identifying a key point for intervention. Study findings will inform clinical practice and GWG guidelines tailored to women with severe pre-pregnancy obesity, both needed to reduce risk in women who enter pregnancy with severe obesity. This study occurs in the context of a well-established collaborative research environment in the developmental origins of disease at O...