Nontargeted Analysis of the Chemical Exposome in Preterm Birth: A Pilot Study of Placenta and Maternal Serum

Abstract Preterm birth is a leading cause of neonatal morbidity and mortality, yet the role of chemical exposures in its etiology remains poorly understood. We hypothesized that untargeted chemical profiling of paired maternal serum and placenta would reveal distinct exposure signatures and metabolic disruptions associated with preterm birth. We analyzed paired maternal serum and placenta samples from 83 pregnant women in New York City, USA, including 30 who delivered preterm (<37 weeks), by non-targeted analysis (NTA) using ultrahigh-performance liquid chromatography coupled to Orbitrap high-resolution mass spectrometry (UHPLC-Orbitrap HRMS). We confirmed 29 chemicals (Level 1), 28 of them exogenous, tentatively identified 1012 peak features (Level 2), and annotated 1180 peak features via in silico simulation (Level 3). Five Level 1 confirmed exogenous chemicals (i.e., dodecyltrimethylammonium, N,N-dimethyldecylamine oxide, rimsulfuron, triphenylphosphine oxide, and 2,6-dichlorobenzamide) and 208 tentatively identified Level 2 chemicals detected in this study appear not to have been previously detected in human blood samples. We identified 119 and 170 significantly differentially enriched features in serum and placenta, respectively (BH-corrected p < 0.05). Serum samples showed changes in glutathione, tryptophan, pyruvate, arachidonic acid, and phospholipid pathways in preterm birth. Our data suggest that chemical exposures might collectively amplify metabolic vulnerabilities in oxidative stress, lipid metabolism, and amino acid catabolism relevant to preterm birth.