Prenatal polycyclic aromatic hydrocarbon (PAH) exposure in relation to placental corticotropin releasing hormone (pCRH) in a sociodemographically diverse U.S. cohort

BACKGROUND AND AIM: Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous endocrine-disrupting combustion by-products that have been linked to preterm birth. One possible mechanism underlying this association is disruption of placental corticotropin releasing hormone (pCRH), a key hormone implicated in parturition. Extending prior research identifying pCRH as a potential target of endocrine disruption, here we examine maternal urinary PAHs in relation to pCRH in the sociodemographically diverse CANDLE cohort, part of the ECHO-PATHWAYS Consortium. METHODS: In a subset of 810 pregnant CANDLE participants, we measured urinary mono-hydroxylated PAH metabolites in Trimester 2 (T2) and serum pCRH in T2 and Trimester 3 (T3). Associations between individual log-transformed PAHs and log(pCRH) (at each timepoint as well as the change over time) were estimated using linear regression models. Minimally adjusted models included gestational age and specific gravity, while fully adjusted models also included sociodemographic characteristics. We additionally evaluated effect modification by factors including pregnancy complications and fetal sex. RESULTS: Participants were 62% Black, 32% White, and mean age 26.8±5.6 years. In minimally adjusted models, most PAH metabolites were inversely associated with pCRH concentrations. For instance, 1-hydroxypyrene was associated with lower T2 (β=-0.10, 95%CI: -0.16, -0.03) and T3 (β=-0.08, 95%CI: -0.15, -0.003) log(pCRH). After adjustment for sociodemographic factors, however, results were attenuated for all PAHs, including associations between 1-hydroxypyrene and log(pCRH) at T2 (β=-0.01, 95%CI: -0.07, 0.06) and T3 (β=0.01, 95%CI: -0.07, 0.08). There was no evidence of effect modification by any factors considered. CONCLUSIONS: In the only epidemiological study of PAHs and pCRH to date, we observed little evidence of association after adjustment for covariates. PAHs may nevertheless affect timing of birth through other mechanisms, such as inflammatory or oxidative stress pathways.