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Background Rising rates of overweight and obesity globally have led to an increasing number of women who enter pregnancy with excess weight, posing significant health risks to mothers and infants. Mobile health interventions, such as smartphone apps, may be a solution to improving pregnancy outcomes, however, limited randomized studies have examined this approach for gestational weight gain (GWG) and postpartum weight retention (PPWR). We report results from a double-blinded, randomized control trial of Goals for Reaching Optimal Wellness ( GROWell ), a mobile app and text-based intervention designed to improve diet quality and associated weight outcomes in pregnant and postpartum women. Methods Women living in California with BMI = 25–42 kg/m 2 and a singleton, uncomplicated pregnancy were recruited via social media or clinic in early pregnancy from January 2021 through March 2023. After completing a baseline survey, participants were randomized to GROWell or an educational control. Participants completed online surveys of diet quality and other health behaviors and self-weighed using study-provided Bluetooth scales. Modified Poisson regression tested for differences in excess GWG and 6-month PPWR. Results Using block randomization in permuted blocks of three based on prepregnancy BMI, race/ethnicity, and recruitment source) 453 racially and ethnically diverse participants (237 attention control, 216 intervention) were enrolled. Mean age was 33.6 ± 4.1 years and mean BMI was 30.9 ± 4.28 kg/m 2 . Excess GWG was observed in 36% of the control group and 35% of the intervention group. PPWR was observed in 26% of the control group and 23% of the intervention group. Conclusions Compared to an attention control, GROWell was not associated with lower rates of excess GWG or PPWR. However, study rates of excess GWG and PPWR were lower in both groups compared to averages in the US and several Western nations. Future studies should investigate the potential of text-based educational support on weight and other health indicators among childbearing women. Trial registration ClinicalTrials.gov identifier NCT04449432. Registered on June 26, 2020.

Objectives/Goals: To identify lipid signatures associated with adverse pregnancy outcomes (APOs) and postpartum weight retention (PPWR) in women entering pregnancy with overweight or obesity and to explore potential epigenetic mechanisms through ongoing DNA methylation (DNAm) analysis. Methods/Study Population: The GROWell: Goals for Reaching Optimal Wellness study was a blinded, randomized clinical trial to improve dietary support during pregnancy and postpartum. Data were collected via online questionnaires, electronic health records (EHRs), and participant-collected dried blood spots (DBS) at 10–16 weeks, 36–38 weeks, and 3 months postpartum. We analyzed DBS data from 49 participants using three lipidomic analytical techniques: weighted lipid correlation network analysis, differential lipid analysis, and partial least squares discriminant analysis. Lipid profiles were characterized and then tested for associations with APOs and PPWR at all three time points. DNAm analysis from the samples is ongoing to determine the epigenetic mechanisms associated with lipid dysregulation and pregnancy outcomes. Results/Anticipated Results: The lipid network analysis revealed positive correlations between specific lipid types and APOs, particularly at 10–16 weeks and postpartum. Notably, triglycerides and phosphatidylcholine were associated with an increased risk of APOs. Additionally, in the third trimester, triglycerides were positively correlated with weight-related variables. Postpartum analysis also showed a positive correlation between elevated triglyceride levels and a history of APOs. The network analysis also revealed positive associations between triglycerides and PPWR, which were most evident at the 36–38 week and postpartum time points. Ongoing methylation analysis is expected to identify genomic regions associated with pregnancy outcomes. Discussion/Significance of Impact: These findings underscore the significant role of lipids in pregnancy outcomes for individuals with overweight or obesity. Identifying lipidomic and methylome biomarkers of risk for APOs and PPWR may help with early detection and intervention, improving maternal and fetal health.