Polycyclic aromatic hydrocarbons (PAHs) contribute to inflammation in a pregnancy cohort

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants generated from incomplete combustion and are detectable in nearly all individuals in the U.S. population. Prenatal PAH exposure has been linked to adverse birth and child health outcomes, but few studies have examined associations between biomarkers of PAHs and inflammation during pregnancy across gestational windows. We investigated associations between urinary PAH metabolites and urinary inflammatory markers among 159 pregnant women enrolled in the placental assessment in response to environmental exposures cohort (2016-2019). Urine samples were collected up to three times during pregnancy (10-17, 18-29, and ⩾30 gestational weeks). Hydroxylated PAHs metabolites were quantified using liquid chromatography-tandem mass spectrometry, and inflammatory markers (IL-6, IL-1β, TNF-α, and IL-10) were measured using immunoassays. Biomarker concentrations were adjusted for urinary dilution using specific gravity and log-transformation. Effect estimates were generated using linear mixed-effect models with random intercept for each participant to account for repeated measures, and linear regression to assess sampling-period-specific associations while adjusting for maternal age, ethnicity/race, parity, education, and BMI. We found that most PAH metabolites, particularly phenanthrene and naphthalene metabolites, are positively associated with urinary inflammatory markers, except for fluorene metabolites. In mixed-effects models, each doubling of urinary PAHs concentrations was associated with approximately 10%-50% increases in IL-6, IL-1β, TNF-α, and IL-10 levels. Sampling period-specific analyses indicated that associations with pro-inflammatory cytokines were stronger in early and mid-pregnancy (10-29 weeks), whereas associations with IL-10 were most pronounced later in pregnancy (⩾30 weeks). Results were robust to the exclusion of participants with preeclampsia. These findings indicate that prenatal PAH exposure is associated with sustained inflammatory activity across pregnancy, with gestational timing-specific patterns that may help explain windows of increased vulnerability for adverse pregnancy outcomes. This longitudinal evidence strengthens biologic plausibility linking environmental PAH exposure to maternal inflammatory processes.