MON-138 - Early Pregnancy Metabotypes Predict Offspring Adiposity and Associate with Modifiable Lifestyle Exposures in the LIFE-Moms Cohort

Background: The LIFE-Moms Consortium evaluated a lifestyle intervention during pregnancy in women with overweight or obesity. Although the intervention improved gestational weight gain, it showed no association with offspring outcomes. Metabotypes refer to subgroups sharing similar metabolic profiles that may influence the effectiveness of lifestyle interventions. This study explores associations between first-trimester metabotype and offspring adiposity, their relationship to dietary, physical activity, sleep, quality of life, and neighborhood exposures, and transitions through pregnancy and postpartum.

Methods: Maternal first-trimester demographics, anthropometrics, glycemic measures, lipids, inflammatory markers, and adipokines (n=18 variables) were clustered using K-means. Cluster number was selected using internal validation metrics (Dindex, Silhouette score, and Calinski-Harabasz index) and visual inspection. The K-means solution was validated against unsupervised hierarchical clustering. Metabotype labels were assigned based on group-level clinical profiles. Multiple linear regression examined associations between metabotype and offspring body composition, adjusting for covariates. First-trimester exposures including diet (ASA24), accelerometry-measured physical activity and sleep, quality of life (SF-12), and neighborhood environment (PANES) were mapped to metabotypes. Metabotype transitions were assessed using the Stuart-Maxwell test and visualized using Alluvial plots.

Results: Three metabotypes were identified among 918 participants: Metabolically Healthy (MH, n=425), with lower weight, glucose, insulin, lipids, and inflammation; Dyslipidemic (DL, n=245), with elevated lipids and adiposity but preserved glycemic function; and Insulin-Resistant (IR, n=248), with elevated glycemic markers, dyslipidemia, and inflammation. Offspring of IR mothers had higher adiposity (p=0.03) compared to MH. IR mothers had 6.3-fold increased GDM risk versus MH. Exposure mapping revealed IR was associated with lower dietary micronutrient intake (vitamin E, choline, folate, iron), reduced moderate-to-vigorous physical activity, shorter sleep duration, and lower SF-12 physical component scores. Metabotype stability from first to third trimester was 58-66%, with 65% of MH mothers returning to their early pregnancy metabotype by one year postpartum. The intervention was not significant in these models, but the study site (intervention type) was associated with differences in metabotype stability.

Conclusion: Early pregnancy metabotypes derived from clinical metrics predicted offspring adiposity and GDM risk. Metabotypes showed consistent associations with modifiable exposures including diet quality, physical activity, sleep, and quality of life, suggesting potential targets for precision interventions in pregnancy.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*