Early-life exposure to a mixture of phthalates and phenols and child social behavior in a new type of mother-child cohort relying on within-subject pools of repeated urine biospecimens

Background and Aim: Previous cohorts characterized exposure to phenols and phthalates using few spot urine samples, incurring in exposure misclassification. Early infancy exposure remains understudied. We relied on a cohort with improved exposure assessment to examine associations of phthalates and phenols with child autistic traits. Methods: This analysis included 406 mother-child pairs from the French SEPAGES cohort. 25 phenols/phthalate metabolites were measured in within-subject pools of repeated urine samples collected at second and third pregnancy trimesters (median= 21 samples/trimester), and at 2 and 12 months of age (median= 7 samples/period). Autistic traits were parent-reported at 3 years using the Social Responsiveness Scale (SRS). Adjusted differences in SRS raw scores were estimated per doubling in each biomarker concentration using linear regression. A literature review was performed to prioritize the measured phthalates/phenols based on their likelihood to affect social behavior. The mixture effect was estimated for the prioritized compounds (bisphenol A, triclosan, DEHP, MEP, MnBP and MBzP) using Bayesian Weighted Quantile Sum (BWQS) regression. Results: Most associations were observed in the 12-months exposure window. Among the prioritized compounds, triclosan (β= 0.79; 95%CI: 0.01, 1.56) and MEP (β= 0.92; 95%CI: -0.11, 1.95) were associated with worse total SRS scores, while MnBP and ∑DEHP were associated with worse social awareness (β= 0.25; 95%CI: 0.01, 0.50), and social communication (β= 0.43; 95%CI: -0.02, 0.88) scores, respectively. The mixture of prioritized compounds was associated with worse total SRS scores (Beta1= 1.40; 95%CrI: -0.22, 2.99), driven by the social awareness (Beta1= 0.36; 95%CrI: 0.03, 0.70) and social communication (Beta1= 0.87; 95%CrI: 0.31, 1.51) subscales. Conclusions: The literature search allowed to prioritize the compounds with a higher weight of evidence. Our results suggest that early infancy is a critical window for the effects of phenols and phthalates on child social development. Keywords: phthalates, bisphenol, neurodevelopment, social behavior, autism