Critical windows of prenatal heat exposure and preterm birth: Metabolomic study in the Atlanta African American Maternal-Child Cohort

Extreme heat is a risk factor for preterm birth (PTB), but the underlying biological pathways remain poorly understood. This study aimed to identify maternal metabolomic signatures associated with prenatal heat exposure and PTB. We conducted a prospective analysis of 215 participants in the Atlanta African American Maternal-Child Cohort (2014 to 2020). Serum samples collected during early and late pregnancy underwent untargeted metabolomic profiling. Daily maximum ambient temperature was estimated at geocoded residential addresses and averaged over three exposure windows: conception to early pregnancy, early to late pregnancy, and conception to late pregnancy. Metabolome-wide association studies were performed for each exposure window and PTB, followed by a meet-in-the-middle analysis. We identified 23 metabolic pathways and four overlapping metabolites, including methionine, proline, citrulline, and pipecolate, associated with both temperature exposure and PTB. These metabolites are involved in amino acid metabolism and oxidative stress regulation. Findings highlight the potential of metabolomics to detect early biological alterations linked to environmental risk and adverse birth outcomes.