Project Summary/Abstract Obesity prevalence has been steadily rising in the U.S. over the past three decades, including among pregnant women, children, and minorities. Accumulating evidence links maternal obesity – particularly severe obesity – to increased risk for obesity and other chronic diseases in their offspring. Moreover, intervention strategies targeting the prenatal period have yielded disappointing results, shifting focus to the preconception period. Utilization of bariatric surgery procedures have become more common, including among women of childbearing age, as it achieves weight losses averaging between 20% and 30% of total body weight (roughly 3-4 times more effective than lifestyle interventions) and is sustained long-term (seven years and longer). However, the risks and benefits of preconception weight loss by bariatric surgery to children are poorly understood, particularly in the longer-term. The overall goal of the proposed research is to determine if surgically-induced preconception weight loss can reduce their offspring's long-term risk of obesity and obesity-related health. We will utilize information collected from a large cohort (n=2120) of women with obesity who lost weight by bariatric surgery before becoming pregnant and their children. We will compare weight and weight related health (size for gestational age, infant weight gain, BMI through 6 years of age) in children of women who received bariatric surgery prior to pregnancy to two control groups born to women who did not undergo bariatric surgery (n=21,200). The first control group will be matched to the mother's pre-surgical BMI; the second control group will be matched to the mother's pre-pregnancy BMI (after surgery). We will then determine the extent to which pregnancy conditions (gestational diabetes mellitus, hypertensive disorders, anemia, gestational weight gain) mediate associations between bariatric surgery and child outcomes. We will further examine if smaller size for gestational age – one known risk following bariatric surgery – is associated with child outcomes similarly in children born to mothers with and without bariatric surgery, and without and without pregnancy anemia. Our large, unique dataset created by a consortium of Kaiser Permanente and Oregon Health & Science University sites, will allow us to address these questions in a diverse study population, with representation of racial and ethnic minority women at highest risk of severe obesity. Study findings will provide understanding of the role of preconception weight loss on long-term child health outcomes, the specific influence of achieving this weight loss by bariatric surgery on these outcomes, and guide future outcome studies that focus on improving maternal preconception weight by lifestyle, medical, and surgical means.