Mixture of Plasticizer Chemicals and Child Intelligence: A Weight-of-Evidence and Meta-Analysis-Informed Bayesian Approach in a Cohort with Improved Exposure Assessment

Early-life exposure to plasticizer chemicals can affect child neurodevelopment. However, accurately characterizing exposure to these short-lived chemicals remains challenging. To address knowledge gaps, we examined the association between prenatal and infant exposure to a plasticizer mixture and child intelligence quotient (IQ) in a cohort with improved exposure assessment, informing the statistical analysis using the existing toxicological and epidemiological evidence. This work included 380 mother-infant pairs from the SEPAGES study, a French new-generation population-based birth cohort recruited between 2014 and 2018. Sixteen phenols and phthalate metabolites were quantified in pools of multiple urine samples collected at four time points during pregnancy and infancy (up to 21/week). Children’s IQ was assessed using the Wechsler Preschool and Primary Scale of Intelligence at age 3. A structured review of the toxicological and epidemiological evidence was conducted to prioritize the chemicals with the highest weight of evidence (WoE) to be analyzed as a mixture. Meta-analyses of the retrieved epidemiological studies were performed and used as priors in single-chemical Bayesian regression models. Of 1189 references screened, we retrieved data from 30 toxicological and 57 epidemiological studies supporting the prioritization of bisphenol A and S, diethylhexyl phthalate metabolites, monoethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), and mono-isobutyl phthalate (MiBP). Each quartile increase in maternal third-trimester concentrations of the high-WoE plasticizer mixture was associated with decreased full-scale (β: -2.86; 95% Credibility Interval, CrI: -5.05, -0.91), visual-spatial (-2.79; 95% CrI: -5.39, -0.82) and verbal (-1.95; 95% CrI: -3.84, 0.00) child IQ scores. Bayesian single-chemical models informed by meta-analysis-based priors also found that third-trimester concentrations of four of the six prioritized chemicals (bisphenol A, MEP, MnBP, and MiBP) were associated with reduced IQ scores. This novel evidence-based framework increased the biological plausibility and external validity of results, supporting that pregnancy exposure to a mixture of common plasticizers affects child IQ and represents a public health concern. The findings underscore the need to protect fetuses and children from plastic-associated chemicals and regulate them by class.