Newborn metabolomic perturbations associated with prenatal tobacco smoke exposure and early birth

BACKGROUND: Exposure to tobacco smoke during pregnancy is an established risk factor for early birth including early term birth (ETB) and preterm birth (PTB). However, the underlying molecular mechanisms are minimally understood. In this study, we aimed to characterize the newborn metabolomic associations with early pregnancy maternal tobacco exposure biomarkers and early birth in 269 mother-child pairs in the Atlanta African American Maternal-Child Cohort (2016-2020). METHODS: Established tobacco exposure biomarkers, cotinine and trans-3'-hydroxycotinine (3HC), were measured in maternal urine samples collected between 8-14 weeks of gestation. Newborn dried blood spots were collected for high-resolution metabolomics profiling. Metabolome-wide association studies and pathway enrichment analyses were conducted to determine metabolomic signals and pathways associated with tobacco exposure biomarkers, ETB, and PTB. RESULTS: We show that biopterin metabolism is a significantly enriched pathway for all exposures and outcomes. Both tobacco exposure biomarkers are associated with riboflavin metabolism. The metabolites riboflavin and 5-hydroxytryptophan are associated with all exposures and outcomes. CONCLUSIONS: Taken together, these findings demonstrate that the newborn metabolome is altered by prenatal tobacco exposure and that these alterations are associated with elevated risks of early birth. Furthermore, perturbation in biopterin metabolism is a potential mechanism linking maternal tobacco exposure to early birth.