Guilbert, Ariane, Rolland, Matthieu, Pin, Isabelle, Thomsen, Cathrine, Sakhi, Amrit, Sabaredzovic, Azemira, Slama, Rémy, Guichardet, Karine, Philippat, Claire, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université Grenoble Alpes (UGA), Norwegian Institute of Public Health [Oslo] (NIPH), ANR-19-CE36-0003,EDeN,Exposition précoces aux perturbateurs endocriniens et neurodéveloppement de l'enfant : le rôle de l'axe hypothalamo-hypophysaire(2019), ANR-12-PDOC-0029,ANR-12-PDOC-0029-01,ANR-12-PDOC-0029-01, ANR-14-CE21-0007,SHALCOH,Expositions prénatales aux phénols et santé de l'enfant : analyse longitudinale(2014), ANR-18-CE36-0005,ETAPE,Exposition prénatale au tabac et à la pollution atmosphérique et effets sur la santé respiratoire et le neurodévelopment de l'enfant: rôle de la méthylation placentaire(2018), ANR-15-IDEX-0002,UGA,IDEX UGA(2015), ANR-15-IDEX-0005,ANR-15-IDEX5 ,ANR-15-IDEX5, European Project: 311765,EC:FP7:ERC,ERC-2012-StG_20111109,E-DOHAD(2013), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), ANR-15-IDEX5ANR-15-IDEX5ANR-15-IDEX-0005, ANR-12-PDOC-0029,PAPER,Grossesse, pollution atmospherique, epigenetique, et sante respiratoire(2012), BARBAGALLO, Maïlys, Exposition précoces aux perturbateurs endocriniens et neurodéveloppement de l'enfant : le rôle de l'axe hypothalamo-hypophysaire - - EDeN2019 - ANR-19-CE36-0003 - AAPG2019 - VALID, Retour Post-Doctorant - Grossesse, pollution atmospherique, epigenetique, et sante respiratoire - - PAPER2012 - ANR-12-PDOC-0029 - PDOC - VALID, Appel à projets générique - Expositions prénatales aux phénols et santé de l'enfant : analyse longitudinale - - SHALCOH2014 - ANR-14-CE21-0007 - Appel à projets générique - VALID, APPEL À PROJETS GÉNÉRIQUE 2018 - Exposition prénatale au tabac et à la pollution atmosphérique et effets sur la santé respiratoire et le neurodévelopment de l'enfant: rôle de la méthylation placentaire - - ETAPE2018 - ANR-18-CE36-0005 - AAPG2018 - VALID, IDEX UGA - - UGA2015 - ANR-15-IDEX-0002 - IDEX - VALID, and Environmentally-induced Developmental Origins of Health and Disease - E-DOHAD - - EC:FP7:ERC2013-02-01 - 2018-01-31 - 311765 - VALID
International audience; 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.