PROJECT SUMMARY/ABSTRACT: Obesity is a national epidemic that frequently begins in early childhood and is known to be passed from mothers to their children, but little is known about how to effectively interrupt this multigenerational cycle. Although the Institute of Medicine recommends that women with obesity lose weight prior to pregnancy, we know of no data that have examined the effects of intentional pre-pregnancy weight loss on future obesity risk. The 2011 Strategic Plan for NIH Obesity Research stressed the need for research on new obesity prevention and treatment programs, and we responded to this call in 2014 with Prepare, a randomized controlled trial of a pre-pregnancy weight loss intervention (NIDDK R01DK0099882). Based on emerging data that the 1st trimester intrauterine environment, determined primarily by pre- pregnancy weight, may be key in obesity transmission, the goal of Prepare was to help women who were overweight or had obesity lose weight by improving their diet and physical activity habits prior to becoming pregnant. The program was effective in helping women lose weight before pregnancy and improving the metabolic milieu in early pregnancy, and was regarded highly favorably by participants. Critically, we do not yet know whether the program has an influence on long-term obesity and metabolic risk or diet and physical activity habits of mothers and their offspring. Extending Prepare beyond its current end date—delivery— offers a unique opportunity to test the hypothesis that intervening on women before pregnancy can affect their long-term obesity and metabolic risk and that of their children. In PrepareD, we propose to follow mothers and their offspring for 3 years after delivery in order to determine the longer-term effect of the Prepare intervention on weight and other anthropometric measures; metabolic markers; and diet and physical activity patterns of mothers and their offspring. The study includes an in-person research visit after the children turn 3 as well as collection and analysis of medical record weights and self-reported questionnaire data over the 3-year period. We will store biological samples collected at the visit in a biorepository in order to conduct future studies about potential epigenetic and microbiome pathways that might link pre-pregnancy weight loss to decreased long-term obesity risk in mothers and their offspring. Through NIDDK bridge funding (R56 DK099882), we have had no break between the RCT and follow-up cohort study. We have begun enrolling and collecting anthropometric measures and biological samples from mother-offspring dyads. This additional funding will enable us to complete enrollment and data collection and determine the effects of the commonly recommended obesity prevention strategy, pre-pregnancy weight loss, on long-term weight and metabolic health of mothers and their offspring. Should our results demonstrate efficacy of pre-pregnancy weight loss over the long term, the Prepare ...