Search

Background: Previous studies aiming at relating exposure to phenols and phthalates with child social behavior characterized exposure using one or a few spot urine samples, resulting in substantial exposure misclassification. Moreover, early infancy exposure was rarely studied., Objectives: We aimed to examine the associations of phthalates and phenols with child social behavior in a cohort with improved exposure assessment and to a priori identify the chemicals supported by a higher weight of evidence., Methods: Among 406 mother-child pairs from the French Assessment of Air Pollution exposure during Pregnancy and Effect on Health (SEPAGES) cohort, 25 phenols/phthalate metabolites were measured in within-subject pools of repeated urine samples collected at the second and third pregnancy trimesters ( ∼ 21 samples/trimester) and at 2 months and 1-year of age ( ∼ 7 samples/period). Social behavior was parent-reported at 3 years of age of the child using the Social Responsiveness Scale (SRS). A structured literature review of the animal and human evidence was performed to prioritize the measured phthalates/phenols based on their likelihood to affect social behavior. Both adjusted linear regression and Bayesian Weighted Quantile Sum (BWQS) regression models were fitted. False discovery rate (FDR) correction was applied only to nonprioritized chemicals., Results: Prioritized compounds included bisphenol A, bisphenol S, triclosan (TCS), diethyl-hexyl phthalate ( Σ DEHP ), mono-ethyl phthalate (MEP), mono- n -butyl phthalate (MnBP), and mono-benzyl phthalate (MBzP). With the exception of bisphenols, which showed a mixed pattern of positive and negative associations in pregnant mothers and neonates, few prenatal associations were observed. Most associations were observed with prioritized chemicals measured in 1-y-old infants: Each doubling in urinary TCS ( β = 0.78 ; 95% CI: 0.00, 1.55) and MEP ( β = 0.92 ; 95% CI: - 0.11 , 1.96) concentrations were associated with worse total SRS scores, whereas MnBP and Σ 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 , 0.89) scores, respectively. BWQS also suggested worse total SRS [ Beta  1 = 1.38 ; 95% credible interval (CrI): - 0.18 , 2.97], Social Awareness ( Beta  1 = 0.37 ; 95% CrI: 0.06, 0.70), and Social Communication ( Beta  1 = 0.91 ; 95% CrI: 0.31, 1.53) scores per quartile increase in the mixture of prioritized compounds assessed in 1-y-old infants. The few associations observed with nonprioritized chemicals did not remain after FDR correction, with the exception of benzophenone-3 exposure in 1-y-old infants, which was suggestively associated with worse Social Communication scores (corrected p = 0.07 )., Discussion: The literature search allowed us to adapt our statistical analysis according to the weight of evidence and create a corpus of experimental and epidemiological knowledge to better interpret our findings. Early infancy appears to be a sensitive exposure window that should be further investigated. https://doi.org/10.1289/EHP11798.

Background: Synthetic phenols and phthalates can interfere with biological pathways involved in brain development. Despite the high within-subject temporal variability of urinary concentrations observed for their metabolites, studies investigating effects of phenols and phthalates on child behaviour often relied on a limited number of spot biospecimens to assess exposure. Besides, the majority did not consider mixture effects., Objectives: To study the combined effect of prenatal exposure to synthetic phenols and phthalates on child behaviour using repeated exposure measurements., Methods: We assessed concentrations of 12 phenols, 13 phthalate and 2 non-phthalate plasticizer metabolites in within-subject pools of multiple urine samples (median = 21 samples per individual pool) collected at two distinct time points during pregnancy in 416 mother-child pairs from the French SEPAGES cohort. Child behaviour was evaluated at two years using the Child Behaviour Checklist 1.5-5 (CBCL). Associations between a mixture of biomarkers of exposure and externalizing and internalizing behaviour scores were studied using adjusted Weighted Quantile Sum (WQS) regressions with a repeated holdout validation (100 repetitions)., Results: The positive WQS indexes were associated with both the externalizing and internalizing behaviour scores in the whole population, indicating greater risk of behavioural problems. Stratification for child sex suggested stronger associations in girls than boys. On average, girls externalizing and internalizing scores increased by 3.67 points (95% CI: 1.24, 6.10) and 2.47 points (95 %CI: 0.60, 4.33) respectively, for an increase of one tertile in the WQS index, compared with 1.70 points (95 %CI: -0.42, 3.81) and 1.17 points (95 %CI: -0.50, 2.84) in boys. Main contributors for the associations observed in girls were bisphenol A (weight of 18%), triclosan (17%) and monoethyl phthalate (MEP, 15%) for the externalizing score and MEP (19%), mono-benzyl phthalate (MBzP, 19%) and mono-n-butyl phthalate (MnBP, 16%) for the internalizing score., Discussion: Our results suggest adverse associations between in utero exposure to a mixture of phenols and phthalates and child behaviour, mainly in girls. Public health consequences may be substantial due to the widespread exposure of the population to these compounds., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)