Association of urinary polycyclic aromatic hydrocarbon metabolites with symptoms among autistic children: A case-control study in Tianjin, China

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous pollutants that are associated with altered neurodevelopment and various neurodevelopmental disorders. However, studies evaluating internal biomarkers of PAH exposure in reference to the severity of autism spectrum disorder (ASD) symptomology and autistic behaviors are scarce. Hence, we conducted a case-control study evaluating 12 urinary hydroxylated PAH metabolites (i.e., hydroxy-PAHs) in 101 children with autism and 101 neurotypical children, matching according to sex and age in a 1:1 ratio. In children with ASD, the severity of symptomology and autistic behaviors were assessed using the child autism rating scale (CARS) and the autism behavior checklist (ABC). We found that urinary levels of nine of the hydroxy-PAHs were statistically significantly higher in the ASD group, with the exception of 2-hydroxynaphthalene (2-OHNap) and 4-hydroxyphenanthrene (4-OHPhe). Moreover, urinary hydroxy-PAH levels were associated with ASD risk, with odds ratios ranging from 1.86 to 17.19. Exposures to 1-hydroxynaphthalene (1-OHNap, β = 3.32), hydroxyphenanthrenes (1/2/3 + 9-OHPhes, β = 3.41-5.12), 1-hydroxypyrene (1-OH-Pyr; β = 3.91), 2-hydroxybenzofuran (2-OHDBF; β = 3.93), and ∑OH-PAHs (β = 4.67) were positively associated with CARS scores after adjusting for covariates (all p < 0.05). When applying the ABC scale, 1-OHPyr levels were positively associated with ABC total scores (β = 18.54), with the strongest associations evidenced in regard to the social relatedness (β = 6.51) and language domains (β = 6.51) (all p < 0.05). Bayesian kernel machine regression (BKMR) showed consistent positive exposure responses for 1-OHNap, 1-OHPhe, and 3 + 9-OHPhe levels in regard to CARS scores, and for 1-OHPyr levels in regard to ABC total scores. Our findings suggest that children with ASD may have higher urinary levels of hydroxy-PAHs, and that these biomarker levels are associated with an increased odds of ASD, an increased severity of autism symptomology, and increased autistic behaviors in children with autism. LAY SUMMARY: We conducted an epidemiologic study evaluating the associations of urinary hydroxy-PAH levels with autism spectrum disorder (ASD), autism symptomology, and autistic behaviors. We found that urinary hydroxy-PAHs were statistically significantly associated with ASD. We note strong statistically significant associations between 1-OHNap, 1-OHPhe, and 3 + 9-OHPhe levels and increased severity of autism symptomology, as well as a strong statistically significant association between 1-OHPyr levels and behavioral characteristics within the social and linguistic domains. This work, if confirmed, will contribute to the future development of diagnostics for children with mild autism, as well as to environmental measures to promote the health and wellbeing of children with autism spectrum disorders.