(P44-30-26) Exploring the Long-Term Effects of Preconception Nutrition: A Preliminary Metabolomics Analysis From the 10-Y Follow Up in the PRECONCEPT Study

Objectives: We examined how maternal micronutrient supplementation before conception influences the offspring metabolome at age 10 y by analyzing dried blood spots (DBS) obtained from children born to women who participated in a randomized controlled trial that was conducted in Vietnam (PRECONCEPT).

Methods: Among 1,599 offspring born to women who received weekly preconception supplements with either folic acid (FA), iron + FA (IFA), or IFA+13 other micronutrients (MM), we selected a random sample of 45 of 773 eligible children (15/group) with DBS samples collected at age 10 y. Untargeted metabolomics with high resolution liquid chromatography (LC)-mass spectrometry was used to identify metabolites in child DBS. Data were analyzed using MetaboAnalyst v6.0 and R v4.4.1, with filtering, mediation normalization, log-transformation, and auto-scaling. ANOVA was used to select discriminatory features using a false discovery rate (FDR) < 0.1, followed by metabolite annotation and pathway enrichment analysis.

Results: Maternal and child baseline and birth characteristics were similar by supplement group and between the analytic and excluded sample. At age 10 y, offspring in the MM group had slightly higher hemoglobin, height and weight; dietary intakes were similar across groups. 1,013 features differed by supplement group in ANOVA and 1,012 of those met FDR < 0.1 from the hydrophilic interaction LC column. Six significantly enriched pathways related to carbohydrate, amino acid, and lipid metabolism were identified using pathway enrichment analysis. Differences in metabolite levels were reported in several metabolic pathways, including linoleate metabolism, carnitine shuttle, carbon fixation, and prostaglandin formation.

Conclusions: Preliminary findings suggest differences in offspring metabolome at age 10 y across supplement groups, suggesting potential mechanistic pathways linking maternal micronutrient supplement and child outcomes. Further analysis in a larger sample of children with maternal baseline and cord blood samples will better inform whether and how preconception nutrition influences offspring metabolic profiles during middle childhood.

Funding Sources: Nestle Foundation, the Mathile Institute for the Advancement of Human Nutrition, the Micronutrient Initiative, and Emory University (NIH P30ES019776)