Prenatal Exposure to Polycyclic Aromatic Hydrocarbons and Cognition in Preschool-Aged Children

Background and aim: Prenatal exposure to polycyclic aromatic hydrocarbons (PAH) is linked to adverse child neurodevelopmental outcomes, including cognition, but epidemiological evidence is inconsistent and little is known about modifying factors or critical windows of exposure. We investigated associations between prenatal PAH exposure and child cognition in a large, multi-site study. Methods: We included nonsmoking mother-child dyads from two prospective pregnancy cohorts (CANDLE and TIDES) in the ECHO-PATHWAYS Consortium. Mono-hydroxylated PAH metabolites (1-hydroxypyrene;1- and 2-hydroxynaphthalene; 1/9-, 2-, and 3-hydroxyphenanthrene; and 2/3/9-hydroxyfluorene) were measured in second trimester urine in both cohorts and additionally in first and third trimesters in TIDES. Full-scale intelligence quotient (FSIQ) was assessed between ages 4-6. Associations between individual PAH metabolites and FSIQ were estimated with multivariable linear regression adjusted for numerous potential confounders. In a TIDES-only sample, we estimated associations with metabolites in each trimester. We assessed modification by child sex and maternal obesity and explored associations of PAH metabolite mixtures with FSIQ using weighted quantile sum regression with a permutation test to control Type I errors. Results: The pooled sample (N =1,223 dyads) spanned five US regions and was sociodemographically diverse. All associations between PAH metabolites, whether assessed individually or as mixtures, and FSIQ were null after full adjustment. Associations were similar across trimesters of exposure (TIDES-only analysis). We did not observe modification by sex or maternal obesity, except in associations between 2-hydroxynaphthalene and FSIQ, which were adverse in males (β_males= -0.67 [95%CI: -1.5, 0.13] and β_females= 0.31 [95%CI: -0.52, 1.1] per two-fold increase in metabolite; p_interaction = 0.04). Conclusion: In this longitudinal multi-cohort analysis with rigorous adjustment for potential confounders, we found little evidence that prenatal PAH exposure adversely impacts cognition in early childhood. Prenatal PAH could exert neurodevelopmental toxicity but affect endpoints other than cognition, such as behavior. Keywords: polycyclic aromatic hydrocarbons; neurodevelopment; mixtures