Prenatal Nitrogen Oxide (NOx) and Its Potential Impact on Infant Metabolism during the First Month of Life: Evidence from Two Distinct Cohorts─The Atlanta African American Maternal-Child Cohort and the Southern California Mother’s Milk Study

Exposure to traffic-related air pollution (TRAP) during pregnancy has been linked with adverse health outcomes, yet the biological mechanisms remain poorly understood. High-resolution metabolomics offers a promising approach to examine how TRAP influences infant health. However, few studies have focused on Black and Latino populations, who are disproportionately exposed to TRAP. This study aims to assess the association between prenatal exposure to TRAP and the infant metabolome in two distinct, geographically independent populations: the prospective Atlanta African American Cohort and the Southern California Mother's Milk Study (MMS). This study provides novel evidence that prenatal nitrogen oxides (NOx), a major component of TRAP, are associated with perturbations in the infant circulating and fecal metabolome during the first month of life. We found that prenatal NOx exposure was linked with the intensity of 8 and 16 level-1 metabolites in the ATL AA and MMS, respectively. Metabolites associated with NOx included several involved in lipid and xenobiotic metabolism. In analyses including untargeted metabolic features, we found that prenatal NOx was associated with perturbations in metabolic pathways including oxidative stress and inflammatory response. These findings provide novel insight into the biological mechanisms by which prenatal TRAP may influence infant health and development.