Single and joint associations of exposure to polycyclic aromatic hydrocarbons with hypertensive disorders of pregnancy: a nested case-control study

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous organic pollutants frequently detected in women of childbearing age. Prenatal PAH exposure has been associated with adverse pregnancy outcomes. However, their impact on hypertensive disorders of pregnancy (HDP) remains unclear. To address this gap, we analyzed urinary levels of 10 PAH metabolites in 516 pregnant women from the Zunyi Birth Cohort using high-performance gas chromatography-tandem mass spectrometry. Multivariate logistic regression assessed associations between individual PAH metabolites and HDP, while Bayesian Kernel Machine Regression (BKMR) was used to evaluate joint and individual effects of PAH mixtures. Weighted quantile sum (WQS) regression and quantile g-computation (QGC) models were applied to estimate the combined exposure effects on HDP risk. Among the 10 PAH metabolites, 2-OH-FLU had the highest detection rate (86.82%), while 4-OH-PHE had the lowest (58.91%). Individual exposure analysis revealed significant associations between HDP risk and 1-OH-NAP (odds ratio [OR]: 1.268; 95% confidence interval [CI]: 1.083–1.484) and 4-OH-PHE (OR: 1.666; 95% CI: 1.212–2.290) concentrations. The BKMR model indicated a positive overall association between PAH mixtures and HDP, with 1-OH-NAP and 4-OH-PHE showing the strongest upward trends. In WQS regression, these two metabolites contributed the most significant positive weights to HDP risk. Similarly, the QGC model revealed a significant association (OR: 1.375; 95% CI: 1.019–1.855) between a quartile increase in PAH mixtures and elevated HDP risk. Our findings indicate that prenatal PAH exposure is associated with increased HDP risk. Further studies are needed to confirm these associations and elucidate underlying biological mechanisms.