Maternal metabolomic signatures for risk of preterm and early term birth in African American women

Metabolic signals identifying pregnancies at risk for preterm birth (<37 weeks) and early term birth (37–38 weeks) remain limited. Here we used high-resolution metabolomics to characterize metabolic features associated with spontaneous and medically indicated early birth. We conducted metabolome-wide association studies among 279 (discovery) and 251 (internal validation) pregnant women from the Atlanta African American Maternal-Child Cohort (2014–2018), with serum collected in early (8–14 weeks) and later (24–30 weeks) pregnancy. Distinct metabolic profiles differentiated spontaneous and medically indicated preterm birth and early term birth across pregnancy windows. Perturbations in amino acid pathways, including arginine, proline, aspartate, glutamate, methionine and cysteine metabolism, were observed. Valine, leucine and tyrosine were inversely associated with spontaneous early birth, while acylcarnitines and aldosterone were associated with medically indicated early birth. Thirteen metabolites were validated, supporting their potential as markers of pregnancies at elevated risk. Metabolites associated with preterm and early term birth were identified in a cohort of African American women, 13 of which were validated in an independent internal dataset, with the potential to be used as markers of at-risk women.