Associations of maternal BMI, GDM, and GWG with offspring metabolomic profiles

Abstract Background Maternal metabolic conditions, including pre-pregnancy body mass index (BMI), gestational diabetes mellitus (GDM), and gestational weight gain (GWG), are key determinants of fetal metabolic programming. However, their independent and combined effects on neonatal metabolomic profiles remain unclear. Methods We analyzed 11 amino acids and 31 acylcarnitines in neonatal heel blood. Participants were stratified by maternal BMI and GDM status. Group differences were assessed using non-parametric tests. Multivariable linear regression models with false discovery rate (FDR) correction were applied to evaluate independent associations of maternal BMI, GDM, and GWG with neonatal metabolites. Mediation and interaction analyses were further conducted. Results Metabolic differences between GDM and non-GDM groups were observed only in the normal BMI subgroup. Maternal BMI was broadly associated with neonatal metabolites, involving both amino acids and acylcarnitines. GDM showed selective associations, including negative correlations with proline and C10:1 and a positive correlation with C3. GWG was positively associated with multiple metabolites without significant negative associations. Mediation analysis indicated that GDM partially mediated the association between BMI and proline. A significant interaction between GDM and GWG was identified, showing combined effects on multiple metabolites. Conclusions Maternal BMI is the main factor associated with neonatal metabolic profiles, while GDM shows metabolite-specific effects and GWG is broadly related to higher metabolite levels. The observed interaction between GDM and GWG suggests that their combined influence on neonatal metabolism should be considered in future studies and clinical assessment.