Maternal Nutritional Adherence and Second-Trimester Amniotic-Fluid Metabolomic Profiles: An Exploratory Study

Background and Objectives: Maternal nutrition during pregnancy has been associated with fetal development and long-term health trajectories through mechanisms potentially involving epigenetic and metabolic programming. However, the molecular mediators linking dietary quality to fetal biochemical profiles remain poorly characterized. This exploratory pilot study aimed to investigate associations between maternal nutritional adequacy and the amniotic-fluid metabolomic profile during the second trimester. Materials and Methods: In this prospective study, AF samples from 41 pregnant women undergoing second-trimester amniocentesis were analyzed using gas chromatography-mass spectrometry (GC-MS). Nutritional status was assessed via the FIGO Nutrition Checklist. Subjects were divided into two groups based on dietary adequacy (FIGO Score >5 vs. ≤5). Multivariate analysis (PLS-DA, VIP scores, volcano plots) and pathway enrichment were performed to identify discriminatory metabolites. Results: Exploratory metabolomic analysis suggested differences between the two nutritional groups. Several candidate metabolites, including stearic acid, lactic acid, proline, and scyllo-inositol, contributed to the observed differences between groups. These features may provide preliminary hypotheses regarding energy-, amino acid-, and lipid-related biochemical pathways. Conclusions: Maternal dietary quality was associated with differences in the amniotic-fluid metabolomic profile. These preliminary findings support further investigation of amniotic-fluid metabolomics as a potential tool for studying the fetal biochemical environment.