Associations between a mixture of phenols and phthalates and child behaviour in a French mother–child cohort with repeated assessment of exposure

•Phenols and phthalates were frequently detected in this recent pregnancy cohort.•Weighted Quantile Sum indexes were associated with child behaviour.•Associations tended to be stronger in girls.•Bisphenol A, triclosan, MEP were the main mixture contributors for externalizing score.•MEP, MBzP, MnBP w...

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Vydané v:Environment international Ročník 156; s. 106697
Hlavní autori: Guilbert, Ariane, Rolland, Matthieu, Pin, Isabelle, Thomsen, Cathrine, Sakhi, Amrit K., Sabaredzovic, Azemira, Slama, Rémy, Guichardet, Karine, Philippat, Claire
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: Elsevier Ltd 01.11.2021
Elsevier
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ISSN:0160-4120, 1873-6750, 1873-6750
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Abstract •Phenols and phthalates were frequently detected in this recent pregnancy cohort.•Weighted Quantile Sum indexes were associated with child behaviour.•Associations tended to be stronger in girls.•Bisphenol A, triclosan, MEP were the main mixture contributors for externalizing score.•MEP, MBzP, MnBP were the main mixture contributors for internalizing score. 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. To study the combined effect of prenatal exposure to synthetic phenols and phthalates on child behaviour using repeated exposure measurements. 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). 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. 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.
AbstractList 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.
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.BACKGROUNDSynthetic 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.To study the combined effect of prenatal exposure to synthetic phenols and phthalates on child behaviour using repeated exposure measurements.OBJECTIVESTo study the combined effect of prenatal exposure to synthetic phenols and phthalates on child behaviour using repeated exposure measurements.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).METHODSWe 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).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.RESULTSThe 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.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.DISCUSSIONOur 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.
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. To study the combined effect of prenatal exposure to synthetic phenols and phthalates on child behaviour using repeated exposure measurements. 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). 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. 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.
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.
•Phenols and phthalates were frequently detected in this recent pregnancy cohort.•Weighted Quantile Sum indexes were associated with child behaviour.•Associations tended to be stronger in girls.•Bisphenol A, triclosan, MEP were the main mixture contributors for externalizing score.•MEP, MBzP, MnBP were the main mixture contributors for internalizing score. 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. To study the combined effect of prenatal exposure to synthetic phenols and phthalates on child behaviour using repeated exposure measurements. 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). 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. 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.
ArticleNumber 106697
Author Guilbert, Ariane
Sabaredzovic, Azemira
Rolland, Matthieu
Philippat, Claire
Pin, Isabelle
Sakhi, Amrit K.
Slama, Rémy
Thomsen, Cathrine
Guichardet, Karine
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  surname: Rolland
  fullname: Rolland, Matthieu
  email: matthieu.rolland@univ-grenoble-alpes.fr
  organization: Team of Environmental Epidemiology Applied to Reproduction and Respiratory Health, Institute for Advanced Biosciences (IAB), Grenoble Alpes University, Inserm, CNRS, 38700 La Tronche, France
– sequence: 3
  givenname: Isabelle
  surname: Pin
  fullname: Pin, Isabelle
  email: ipin@chu-grenoble.fr
  organization: Team of Environmental Epidemiology Applied to Reproduction and Respiratory Health, Institute for Advanced Biosciences (IAB), Grenoble Alpes University, Inserm, CNRS, 38700 La Tronche, France
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  organization: Norwegian Institute of Public Health, Oslo, Norway
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  givenname: Amrit K.
  surname: Sakhi
  fullname: Sakhi, Amrit K.
  email: AmritKaur.Sakhi@fhi.no
  organization: Norwegian Institute of Public Health, Oslo, Norway
– sequence: 6
  givenname: Azemira
  surname: Sabaredzovic
  fullname: Sabaredzovic, Azemira
  email: Azemira.Sabaredzovic@fhi.no
  organization: Norwegian Institute of Public Health, Oslo, Norway
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  givenname: Rémy
  surname: Slama
  fullname: Slama, Rémy
  email: remy.slama@univ-grenoble-alpes.fr
  organization: Team of Environmental Epidemiology Applied to Reproduction and Respiratory Health, Institute for Advanced Biosciences (IAB), Grenoble Alpes University, Inserm, CNRS, 38700 La Tronche, France
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  surname: Guichardet
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  givenname: Claire
  surname: Philippat
  fullname: Philippat, Claire
  email: claire.philippat@univ-grenoble-alpes.fr
  organization: Team of Environmental Epidemiology Applied to Reproduction and Respiratory Health, Institute for Advanced Biosciences (IAB), Grenoble Alpes University, Inserm, CNRS, 38700 La Tronche, France
BackLink https://inserm.hal.science/inserm-03269494$$DView record in HAL
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ADEZE
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BLECG
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K-O
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KOM
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AGQPQ
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ID FETCH-LOGICAL-c521t-2f80a7d5efecbb754ba6f0908765fd6ada01c03b309bcc42ee98d2108c5ba5ed3
IEDL.DBID DOA
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ISSN 0160-4120
1873-6750
IngestDate Fri Oct 03 12:30:23 EDT 2025
Tue Oct 14 20:51:08 EDT 2025
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Sat Nov 29 07:23:35 EST 2025
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IsDoiOpenAccess true
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Keywords DiNCH
Weighted quantile sum regression
ohMPHP
MEHP
DiNP
ohMiNCH
MMCHP
MBzP
SD
SE
DBP
DiBP
oxo-MiNP
Bisphenols
ΣDiNP
DEHP
CBCL
Child behavior
FWER
LOD
MEOHP
MEHHP
CI
IQR
MnBP
Phthalates
Prenatal exposure
MiBP
LOQ
ΣDEHP
DPHP
OH-MiNP
ΣDiNCH
MECPP
oxoMiNCH
WQS
MEP
Triclosan
cx-MiNP
Language English
License This is an open access article under the CC BY-NC-ND license.
Distributed under a Creative Commons Attribution 4.0 International License: http://creativecommons.org/licenses/by/4.0
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content type line 23
ORCID 0000-0002-8076-5550
0000-0002-7529-6999
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  year: 2021
  text: November 2021
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PublicationTitle Environment international
PublicationYear 2021
Publisher Elsevier Ltd
Elsevier
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Snippet •Phenols and phthalates were frequently detected in this recent pregnancy cohort.•Weighted Quantile Sum indexes were associated with child...
Synthetic phenols and phthalates can interfere with biological pathways involved in brain development. Despite the high within-subject temporal variability of...
Background: Synthetic phenols and phthalates can interfere with biological pathways involved in brain development. Despite the high within-subject temporal...
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SubjectTerms biomarkers
bisphenol A
Bisphenols
brain
Child behavior
children
Cognitive science
environment
Life Sciences
maternal exposure
metabolites
Phthalates
plasticizers
pregnancy
Prenatal exposure
public health
risk
Santé publique et épidémiologie
temporal variation
Triclosan
urine
Weighted quantile sum regression
Title Associations between a mixture of phenols and phthalates and child behaviour in a French mother–child cohort with repeated assessment of exposure
URI https://dx.doi.org/10.1016/j.envint.2021.106697
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Volume 156
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