Pregnancyas a Susceptible Period to Ambient Air PollutionExposure on the Maternal Postpartum Metabolome

Pregnancy is a potential critical window to air pollution exposure for long-term maternal metabolic effects. However, little is known about potential early metabolic mechanisms linking air pollution to maternal metabolic health. We included 544 pregnant Mexican women with both ambient PM_2.5 levels during pregnancy and untargeted serum metabolomics to examine associations between pregnancy PM_2.5 exposure (overall and monthly) and postpartum metabolites, implementing FDR-adjusted robust linear regression controlling for covariates. Pathway enrichment analyses (in Reactome and MetaboAnalyst) and effect modification by fetal sex and folic acid supplementation were also evaluated. Higher PM_2.5 exposure levels throughout pregnancy were associated with higher bile acids and amino acids, dysregulated glycerophospholipids, or lower fatty acyl levels (FDR < 0.05), among other metabolites. Potential critical windows of susceptibility to monthly PM_2.5 on metabolites were observed in early to midpregnancy (FDR < 0.005). Main findings were consistent by strata of fetal sex and folic acid supplementation. Metabolic pathways corresponding to positive PM_2.5-metabolite associations indicated enriched bile acid, dietary lipid, and transmembrane transport metabolism, whereas for negative PM_2.5-metabolite associations, we identified altered pathways involving adipogenesis, incretin peptide hormone, GLP-1, PPAR-alpha, and fatty acid receptors (FDR < 0.05). PM_2.5 exposures during pregnancy, especially in early gestation, altered maternal postpartum lipids as well as amino acid metabolism.