Association between prenatal exposure to polycyclic aromatic hydrocarbons and neonatal birth outcomes: Cross-sectional study

This study sought to characterize the concentrations of urinary polycyclic aromatic hydrocarbon (PAH) metabolites in pregnant women across gestational stages and to explore their associations with neonatal birth outcomes. A total of 3689 pregnant women aged 20-45 years were recruited, among whom 866 provided urine samples during early pregnancy and 2833 during late pregnancy. We observed that urinary PAH metabolite concentrations were consistently higher in late pregnancy than in early pregnancy. Regression analyses demonstrated that in early pregnancy, prior to sex stratification, 4-hydroxy phenanthrene (4-OHPh) was associated with neonatal birth weight. Following sex stratification, only 1-hydroxy pyrene (1-OHPYR) was linked to birth parity in male neonates. In late pregnancy, unstratified analyses identified associations of 4-OHPh, 9-hydroxy phenanthrene (9-OHPH), and 3-hydroxy phenanthrene (3-OHPH) with both birth weight and birth length. Sex-stratified analyses for late pregnancy further revealed that 4-OHPh was associated with birth weight and parity in female neonates, with no sex-specific differences detected for other metabolites. Restricted cubic spline (RCS) analyses uncovered nonlinear exposure-response relationships between PAH metabolites and birth outcomes. In early pregnancy, prior to sex stratification, 2-hydroxy phenanthrene (2-OHPh) was associated with birth weight and parity; post-stratification, distinct sex-specific nonlinear associations emerged for different metabolites. A comparable pattern of sex-specific nonlinear relationships was observed for multiple metabolites in late pregnancy. Bayesian kernel machine regression (BKMR) analyses of PAH metabolite mixtures revealed that in early pregnancy, overall PAH metabolite exposure was negatively associated with birth weight and parity, and positively associated with birth length. This trend was consistent in both male and female neonates following sex stratification. In late pregnancy, unstratified BKMR analyses identified an inverted S-shaped exposure-response correlation between PAH metabolite mixtures and birth outcomes, with distinct sex-specific correlation patterns emerging after stratification. Collectively, our findings confirm that prenatal PAH metabolite exposure exhibits associations with neonatal birth outcomes, accompanied by discernible dose-response relationships and sex-specific differences across gestational stages.