Pregnancy as a Susceptible Period to Ambient Air Pollution Exposure 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 PM2.5 levels during pregnancy and untargeted serum metabolomics to examine associations between pregnancy PM2.5 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 PM2.5 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 PM2.5 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 PM2.5-metabolite associations indicated enriched bile acid, dietary lipid, and transmembrane transport metabolism, whereas for negative PM2.5-metabolite associations, we identified altered pathways involving adipogenesis, incretin peptide hormone, GLP-1, PPAR-alpha, and fatty acid receptors (FDR < 0.05). PM2.5 exposures during pregnancy, especially in early gestation, altered maternal postpartum lipids as well as amino acid metabolism.