Unraveling the Molecular Links between Fine Particulate Matter Exposure and Early Birth Risks in African American Mothers: A Metabolomics Study in the Atlanta African American Maternal-Child Cohort

In the United States, African Americans (AA) are disproportionately exposed to elevated levels of ambient fine particulate matter (PM_2.5) while suffering from the highest rates of early births. To elucidate the largely unknown underlying mechanism, we analyzed serum metabolomics from 330 participants in the Atlanta AA Maternal-Child Cohort and performed high-throughput mediation analysis to identify intermediate metabolites and pathways linking PM_2.5 to early births. Energy-metabolism-related metabolites (carnitine and adenosine triphosphate), along with lysoPE(20:3) and acetylcysteine, were both associated with PM_2.5 exposure and elevated early birth risks. Perturbations in protein digestion and absorption and aromatic amino acid (phenylalanine, tyrosine, and tryptophan) metabolism may potentially mediate the associations between PM_2.5 and early births. We identified significant indirect effects of cortexolone (Proportion mediated: −11.8%) and lysoPE(20:3) (9.4%) in mediating the relationship between PM_2.5 and early births. Our findings might aid in early birth prevention among AA communities by providing novel insights into the underlying biological mechanism.