Prenatal exposure to metal mixtures and the risk of overweight and obesity in school-aged children: insights from metabolomic profiling

Background Prenatal metal mixtures exposure was associated with child growth. However, long-term impact of maternal metal mixture exposure on offspring's overweight or obesity (OWO) in childhood and the potential role of metabolites remain poorly understood. Methods Based on a prospective cohort study, ten metals were measured and metabolomics profiling was conducted in maternal serum during pregnancy. Children's anthropometric parameters were measured at school age and OWO was defined according to the international World Health Organization (WHO) reference data. A combination of multiple regression models, variable selection models and exposome models were conducted to explore the effects of prenatal metal mixture exposure on child OWO and BMI z -score. A meet-in-the-middle (MITM) approach was employed to examine metabolites' potential role in mediating this association. Results Maternal metals exposure such as Cu and V was found to be positively associated with OWO risk based on single-metal models, with ORs being 24.171 (95% CI : 2.351–403.256) and 2.534 (95% CI : 1.273–5.623), respectively. Similarly, prenatal exposure to V was also positively associated with BMI z -scores in school-aged children (β: 0.293, 95% CI : 0.015–0.572). Marginal association was found between Cu exposure and BMI z -scores (β: 0.758, 95% CI : −0.001–1.517). Metabolites such as glycerophosphocholine and glycine played potential intermediate roles in the association between maternal Cu levels and OWO risk. Conclusion Prenatal Cu and V exposure may have an adverse effect on school-aged childhood's OWO risk, and metabolites may play an important intermediate role. By further examining metabolite profiles, our findings offer insight into potential metabolic pathways through which prenatal metal exposure may influence childhood obesity risk, thereby extending existing epidemiological evidence with a mechanistic perspective. Multi-center population studies and in vivo studies in future are needed to validate the results.