11 research outputs found

    Prenatal exposure to phenols and phthalates, child neurodevelopment and the role of the thyroid hormones

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    Contexte: L'augmentation rapide de la prévalence de certains troubles du neurodéveloppement nécessite une meilleure compréhension des facteurs de risque modifiables de ces troubles. Les femmes enceinte sont constamment exposés à plusieurs des phénols et les phtalates qui sont des perturbateurs endocriniens liés à divers effets neurotoxiques dans les études toxicologiques. L'un des mécanismes sous-jacents à ces effets pourrait être une action de ces composés sur l’axe thyroïdien.Objectifs: 1) De documenter si l'utilisation de produits de soin personnel pourrait influencer les concentrations urinaires de biomarqueurs d’exposition aux phénols chez les femmes enceintes; 2) d’évaluer les associations entre l'exposition prénatale aux phénols et aux phtalates et le neurodéveloppement des enfants; et 3) d’évaluer les associations entre l'exposition prénatale aux phénols et aux phtalates et les concentrations d'hormones thyroïdiennes chez la femme enceinte et le nouveau-né.Méthodes: Ce travail s’appuie sur trois cohortes françaises complémentaires; l’étude SEPAGES-faisabilité pour lesquelles nous disposions de multiples échantillons d'urine et d'informations détaillées sur leurs utilisations de produits de soin, la cohorte EDEN avec les concentrations urinaires maternelles de phénols et phtalates et, l’information sur la neurodéveloppement des enfants et la cohorte SEPAGES avec les concentrations urinaires maternelles de phénols et phtalates et le taux d'hormones thyroïdiennes pendant la grossesse et à la naissance.Résultats: Le nombre total d'utilisation de produits de soin était associé à une augmentation des concentrations urinaires de bisphénol S et des parabènes mais pas des autres phénols.Aucun des composés étudiés n’était associé négativement aux scores de quotient intellectuel. Les concentrations urinaires maternelles de bisphénol A étaient associées à plus de symptômes de type troubles relationnels à 3 ans et de comportements de type hyperactif à 5 ans. Le MnBP était associé à une augmentation des scores liés aux troubles émotionnels et relationnels à 3 ans, tandis que le MBzP était lui associé à une augmentation des scores liés aux troubles internalisés et les troubles relationnels. Enfin lorsque les scores de comportement étaient étudiés en tant que variables binaires, une association entre le triclosan et les scores liés aux troubles émotionnels était observée à 3 et 5 ans.Les concentrations urinaires de bisphénol A étaient négativement associées aux concentrations de thyréostimuline (TSH) maternelles tandis que le MBzP, était lui positivement associé aux Z-scores de thyroxine totale et le triclosan négativement associé au ratio TT3/TT4. Lorsque les expositions étaient étudiées en terciles, des relations non linéaires ont aussi été observées entre le triclosan et la TSH (relation en U) et le MnBP et la TSH (U inversé). Pour les nouveau-nés, après stratification sur le sexe, les concentrations urinaires maternelles de bisphénol A étaient positivement associées au niveau de TT4 chez les garçons tandis que le triclosan était négativement associé à cette hormone chez les filles.Conclusion: Les associations positives entre l’utilisation de produits de soin et les concentrations urinaires de parabènes étaient en accord avec les études précédentes sur le sujet. Notre étude était la première à mettre en évidence de telles associations avec le bisphénol S. Les associations observées entre les expositions prénatales au bisphénol A et au DBP et le comportement avaient déjà été mis en évidence dans des études précédentes chez de jeunes garçons. Pour ce qui est du triclosan notre étude était la première à s’intéresser aux associations avec le comportement. Les composés associés au comportement dans la cohorte EDEN ont tous été associés à au moins une hormone thyroidienne dans la cohorte SEPAGES, suggérant une possible perturbation de l'homéostasie des hormones thyroïdiennes.Context: The increase in the prevalence of neurodevelopmental disorders warrants identification of the possible underlying modifiable risk factors. Pregnant women are constantly exposed to several phenols and phthalates that are endocrine disrupting chemicals and have been linked to various adverse neurodevelopmental outcomes in toxicological studies. One of the suggested mechanisms of neurotoxicity of these compounds is by disruption of the thyroid hormone pathway.Aims: 1) To document if the use of personal care products (PCP) could influence phenols biomarkers concentrations during pregnancy; 2) to assess associations between prenatal exposure to phenols and phthalates and child neurodevelopment; and 3) to assess associations between prenatal exposure to phenols and phthalates on the thyroid hormone levels of pregnant women and their newborns.Methods: We relied on three complementary cohorts; the SEPAGES-feasibility study with multiple urine samples and detailed, time-resolved information on PCP use, the EDEN cohort with maternal urinary concentrations of phenols, phthalates and information on child neurodevelopment and the SEPAGES cohort with information on gestational exposure to phenols and phthalates (assessed in 2 pools of 21 urine sample per participant) and levels of thyroid hormones levels during pregnancy and at birth.Results: The total number of PCP applications (without distinction) was positively associated with the parabens’ and bisphenol S urinary concentrations during pregnancy but not with other phenols assessed (benzophenone-3, triclosan and bisphenol A).No phenol or phthalate metabolite pregnancy concentration was negatively associated with IQ of boys at 5 years. Some associations with child behavior were observed at 3 and 5 years: Bisphenol A was positively associated with the relationship problems subscale at 3 years and the hyperactivity–inattention subscale scores at 5 years. Mono-n-butyl phthalate (MnBP) was positively associated with internalizing behavior, relationship problems, and emotional symptom scores at 3 years. Monobenzyl phthalate (MBzP) was positively associated with internalizing behavior and relationship problems scores at 3 years. After dichotomizing behavioral scores, triclosan tended to be positively associated with emotional symptom subscales at both 3 and 5 years.Regarding the associations with maternal hormones, bisphenol A was negatively associated with the Ln (TSH) z-score; MBzP, a metabolite of benzylbutyl phthalate (BBP), was positively associated with the TT4 z-score and triclosan was negatively associated with the TT3/TT4 ratio z-score. When biomarker concentrations were categorized in tertiles, we observed non-monotonic associations between TSH and triclosan (U-shape) and MnBP, a metabolite of di-n-butyl phthalate (DBP) (inverse U-shape). In newborns, only sex-specific effects were observed: bisphenol A was positively associated with the TT4 z-score in male newborns while triclosan was negatively associated with the TT4 z-score in females.Conclusion: Findings in this study concur with previous literature that PCPs use may contribute to exposure to parabens. Our study was the first to report associations between PCP use and bisphenol S, a substitute of bisphenol A. In line with previous studies, bisphenol A and various phthalates, including DBP and BBP exposure during pregnancy, were associated adverse behavioral symptoms among boys. Our study was the first to report adverse neurobehavioral effects in relation to triclosan exposure. The four compounds associated with adverse behavioral effects in EDEN were also associated with one or more thyroid hormone levels of mothers or newborns in the SEPAGES cohort, suggesting possible disruption of thyroid hormones homeostasis

    Exposition prénatale aux phénols et aux phtalates, développement neurologique de l'enfant et rôle des hormones thyroïdiennes

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    Context: The increase in the prevalence of neurodevelopmental disorders warrants identification of the possible underlying modifiable risk factors. Pregnant women are constantly exposed to several phenols and phthalates that are endocrine disrupting chemicals and have been linked to various adverse neurodevelopmental outcomes in toxicological studies. One of the suggested mechanisms of neurotoxicity of these compounds is by disruption of the thyroid hormone pathway.Aims: 1) To document if the use of personal care products (PCP) could influence phenols biomarkers concentrations during pregnancy; 2) to assess associations between prenatal exposure to phenols and phthalates and child neurodevelopment; and 3) to assess associations between prenatal exposure to phenols and phthalates on the thyroid hormone levels of pregnant women and their newborns.Methods: We relied on three complementary cohorts; the SEPAGES-feasibility study with multiple urine samples and detailed, time-resolved information on PCP use, the EDEN cohort with maternal urinary concentrations of phenols, phthalates and information on child neurodevelopment and the SEPAGES cohort with information on gestational exposure to phenols and phthalates (assessed in 2 pools of 21 urine sample per participant) and levels of thyroid hormones levels during pregnancy and at birth.Results: The total number of PCP applications (without distinction) was positively associated with the parabens’ and bisphenol S urinary concentrations during pregnancy but not with other phenols assessed (benzophenone-3, triclosan and bisphenol A).No phenol or phthalate metabolite pregnancy concentration was negatively associated with IQ of boys at 5 years. Some associations with child behavior were observed at 3 and 5 years: Bisphenol A was positively associated with the relationship problems subscale at 3 years and the hyperactivity–inattention subscale scores at 5 years. Mono-n-butyl phthalate (MnBP) was positively associated with internalizing behavior, relationship problems, and emotional symptom scores at 3 years. Monobenzyl phthalate (MBzP) was positively associated with internalizing behavior and relationship problems scores at 3 years. After dichotomizing behavioral scores, triclosan tended to be positively associated with emotional symptom subscales at both 3 and 5 years.Regarding the associations with maternal hormones, bisphenol A was negatively associated with the Ln (TSH) z-score; MBzP, a metabolite of benzylbutyl phthalate (BBP), was positively associated with the TT4 z-score and triclosan was negatively associated with the TT3/TT4 ratio z-score. When biomarker concentrations were categorized in tertiles, we observed non-monotonic associations between TSH and triclosan (U-shape) and MnBP, a metabolite of di-n-butyl phthalate (DBP) (inverse U-shape). In newborns, only sex-specific effects were observed: bisphenol A was positively associated with the TT4 z-score in male newborns while triclosan was negatively associated with the TT4 z-score in females.Conclusion: Findings in this study concur with previous literature that PCPs use may contribute to exposure to parabens. Our study was the first to report associations between PCP use and bisphenol S, a substitute of bisphenol A. In line with previous studies, bisphenol A and various phthalates, including DBP and BBP exposure during pregnancy, were associated adverse behavioral symptoms among boys. Our study was the first to report adverse neurobehavioral effects in relation to triclosan exposure. The four compounds associated with adverse behavioral effects in EDEN were also associated with one or more thyroid hormone levels of mothers or newborns in the SEPAGES cohort, suggesting possible disruption of thyroid hormones homeostasis.Contexte: L'augmentation rapide de la prévalence de certains troubles du neurodéveloppement nécessite une meilleure compréhension des facteurs de risque modifiables de ces troubles. Les femmes enceinte sont constamment exposés à plusieurs des phénols et les phtalates qui sont des perturbateurs endocriniens liés à divers effets neurotoxiques dans les études toxicologiques. L'un des mécanismes sous-jacents à ces effets pourrait être une action de ces composés sur l’axe thyroïdien.Objectifs: 1) De documenter si l'utilisation de produits de soin personnel pourrait influencer les concentrations urinaires de biomarqueurs d’exposition aux phénols chez les femmes enceintes; 2) d’évaluer les associations entre l'exposition prénatale aux phénols et aux phtalates et le neurodéveloppement des enfants; et 3) d’évaluer les associations entre l'exposition prénatale aux phénols et aux phtalates et les concentrations d'hormones thyroïdiennes chez la femme enceinte et le nouveau-né.Méthodes: Ce travail s’appuie sur trois cohortes françaises complémentaires; l’étude SEPAGES-faisabilité pour lesquelles nous disposions de multiples échantillons d'urine et d'informations détaillées sur leurs utilisations de produits de soin, la cohorte EDEN avec les concentrations urinaires maternelles de phénols et phtalates et, l’information sur la neurodéveloppement des enfants et la cohorte SEPAGES avec les concentrations urinaires maternelles de phénols et phtalates et le taux d'hormones thyroïdiennes pendant la grossesse et à la naissance.Résultats: Le nombre total d'utilisation de produits de soin était associé à une augmentation des concentrations urinaires de bisphénol S et des parabènes mais pas des autres phénols.Aucun des composés étudiés n’était associé négativement aux scores de quotient intellectuel. Les concentrations urinaires maternelles de bisphénol A étaient associées à plus de symptômes de type troubles relationnels à 3 ans et de comportements de type hyperactif à 5 ans. Le MnBP était associé à une augmentation des scores liés aux troubles émotionnels et relationnels à 3 ans, tandis que le MBzP était lui associé à une augmentation des scores liés aux troubles internalisés et les troubles relationnels. Enfin lorsque les scores de comportement étaient étudiés en tant que variables binaires, une association entre le triclosan et les scores liés aux troubles émotionnels était observée à 3 et 5 ans.Les concentrations urinaires de bisphénol A étaient négativement associées aux concentrations de thyréostimuline (TSH) maternelles tandis que le MBzP, était lui positivement associé aux Z-scores de thyroxine totale et le triclosan négativement associé au ratio TT3/TT4. Lorsque les expositions étaient étudiées en terciles, des relations non linéaires ont aussi été observées entre le triclosan et la TSH (relation en U) et le MnBP et la TSH (U inversé). Pour les nouveau-nés, après stratification sur le sexe, les concentrations urinaires maternelles de bisphénol A étaient positivement associées au niveau de TT4 chez les garçons tandis que le triclosan était négativement associé à cette hormone chez les filles.Conclusion: Les associations positives entre l’utilisation de produits de soin et les concentrations urinaires de parabènes étaient en accord avec les études précédentes sur le sujet. Notre étude était la première à mettre en évidence de telles associations avec le bisphénol S. Les associations observées entre les expositions prénatales au bisphénol A et au DBP et le comportement avaient déjà été mis en évidence dans des études précédentes chez de jeunes garçons. Pour ce qui est du triclosan notre étude était la première à s’intéresser aux associations avec le comportement. Les composés associés au comportement dans la cohorte EDEN ont tous été associés à au moins une hormone thyroidienne dans la cohorte SEPAGES, suggérant une possible perturbation de l'homéostasie des hormones thyroïdiennes

    In-utero exposure to phenols and phthalates and the intelligence quotient of boys at 5 years

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    Abstract Background There are concerns that developmental exposure to endocrine disrupting chemicals such as phenolic compounds and phthalates could affect child cognitive function. Epidemiological studies tackling this question have mainly focused on phthalate metabolites and bisphenol A, but not on the other phenolic compounds. Our study aimed to assess the relationship between in-utero exposure to phthalates, bisphenol A and other phenolic compounds (parabens, triclosan, dichlorophenols and benzophenone-3) and the Intelligence Quotient (IQ) of boys at 5–6 years. Methods In 452 mother-son dyads from the French EDEN cohort, we measured 11 phthalate metabolites and 9 phenolic compounds (4 parabens, benzophenone-3, bisphenol A, 2 dichlorophenols and triclosan) in spot urine samples collected between 22 and 29 gestational weeks. Verbal and performance IQ of children were assessed at 5–6 years by a psychologist using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI). We used adjusted Structural Equation Models (SEM) combined with Benjamini and Hochberg false discovery rate correction to assess the associations between maternal urine phenol and phthalate metabolite concentrations considered simultaneously and the boys’ IQ. Results No phenol or phthalate metabolite concentration was negatively associated with the boys’ verbal or performance IQ (uncorrected p-values ≥0.09). Mono(3-carboxypropyl) phthalate tended to be associated with increased verbal IQ (β = 0.136, 95% confidence interval, 0.01; 0.27). This association disappeared after correction for multiple comparison (corrected p-value, 0.71). Conclusion Our results did not provide evidence of an inverse association between in-utero exposure to phenols or phthalates and verbal and performance IQ among boys. Since phenols and phthalates may have sex-specific effects, these null findings cannot be generalized to girls. Limitations included use of a single spot urine sample to assess exposures and lack of consideration of postnatal exposures

    Exposure to a mixture of non-persistent environmental chemicals and neonatal thyroid function in a cohort with improved exposure assessment

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    International audienceBackground: In vitro and toxicological studies have shown that non-persistent environmental chemicals can perturb thyroid hormone homeostasis. Epidemiological studies with improved exposure assessment (i.e., repeated urine samples) are needed to evaluate effects of these compounds, individually or as a mixture, in humans. We studied the associations between prenatal exposure to non-persistent environmental chemicals and neonatal thyroid hormones.Methods: The study population consisted of 442 mother–child pairs from the French SEPAGES mother–child cohort recruited between July 2014 and July 2017. For each participant, four parabens, five bisphenols, tri- closan, triclocarban, benzophenone-3 as well as metabolites of phthalates and of di(isononyl)cyclohexane-1,2- dicarboxylate were assessed in two pools of repeated urine samples (median: 21 spot urines per pool), collected in the 2nd and 3rd trimesters of pregnancy, respectively. Thyroid stimulating hormone (TSH) and total thyroxine (T4) levels were determined in newborns from a heel-prick blood spot. Maternal iodine and selenium were assessed in urine and serum, respectively. Adjusted linear regression (uni-pollutant model) and Bayesian Kernel Machine Regression (BKMR, mixture model) were applied to study overall and sex-stratified associations between chemicals and hormone concentrations.Results: Interaction with child sex was detected for several compounds. Triclosan, three parabens, and one phthalate metabolite (OH-MPHP) were negatively associated with T4 among girls in the uni-pollutant model. BKMR also suggested a negative association between the mixture and T4 in girls, whereas in boys the association was positive. The mixture was not linked to TSH levels, and for this hormone the uni-pollutant model revealed associations with only a few compounds.Conclusion: Our study, based on repeated urine samples to assess exposure, showed that prenatal exposure to some phenols and phthalates disturb thyroid hormone homeostasis at birth. Furthermore, both uni-pollutant and mixture models, suggested effect modification by child sex, while, to date underlying mechanisms for such sex-differences are not well understood

    Exposure to a mixture of non-persistent environmental chemicals and neonatal thyroid function in a cohort with improved exposure assessment

    No full text
    Background: In vitro and toxicological studies have shown that non-persistent environmental chemicals can perturb thyroid hormone homeostasis. Epidemiological studies with improved exposure assessment (i.e., repeated urine samples) are needed to evaluate effects of these compounds, individually or as a mixture, in humans. We studied the associations between prenatal exposure to non-persistent environmental chemicals and neonatal thyroid hormones. Methods: The study population consisted of 442 mother–child pairs from the French SEPAGES mother–child cohort recruited between July 2014 and July 2017. For each participant, four parabens, five bisphenols, triclosan, triclocarban, benzophenone-3 as well as metabolites of phthalates and of di(isononyl)cyclohexane-1,2-dicarboxylate were assessed in two pools of repeated urine samples (median: 21 spot urines per pool), collected in the 2nd and 3rd trimesters of pregnancy, respectively. Thyroid stimulating hormone (TSH) and total thyroxine (T4) levels were determined in newborns from a heel-prick blood spot. Maternal iodine and selenium were assessed in urine and serum, respectively. Adjusted linear regression (uni-pollutant model) and Bayesian Kernel Machine Regression (BKMR, mixture model) were applied to study overall and sex-stratified associations between chemicals and hormone concentrations. Results: Interaction with child sex was detected for several compounds. Triclosan, three parabens, and one phthalate metabolite (OH-MPHP) were negatively associated with T4 among girls in the uni-pollutant model. BKMR also suggested a negative association between the mixture and T4 in girls, whereas in boys the association was positive. The mixture was not linked to TSH levels, and for this hormone the uni-pollutant model revealed associations with only a few compounds. Conclusion: Our study, based on repeated urine samples to assess exposure, showed that prenatal exposure to some phenols and phthalates disturb thyroid hormone homeostasis at birth. Furthermore, both uni-pollutant and mixture models, suggested effect modification by child sex, while, to date underlying mechanisms for such sex-differences are not well understood

    Use of personal care products during pregnancy in relation to urinary concentrations of select phenols: A longitudinal analysis from the SEPAGES feasibility study

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    International audienceBackground: Exposure to certain synthetic phenols is of growing concern, in particular among pregnant women, because of their endocrine disrupting nature. Many phenols are still authorized in personal care products (PCP). We aimed to assess if use of PCPs, by pregnant women could influence their urinary concentrations of synthetic phenols.Methods: We used a panel design with intense urine sample collection. Eight women completed a diary with exact time and use of PCPs in three weeks. We measured the concentrations of phenols (four parabens, bisphenol A and S, two dichlorophenols, triclosan, and benzophenone-3) in 178 urine samples, collected during 7 consecutive days at 3 time points during pregnancy. We characterized PCP use as the total number of PCP applications or as a single PCP use (yes/no) in three time windows (0–6, 6 to 12 and 12 to 24h before each urine sample collection). We used adjusted linear and Tobit regressions to assess associations between PCP use and phenol urinary concentrations.Results: The total number of PCP applications was positively associated with ethylparaben, propylparaben and butylparaben concentrations. We observed a peak in urinary concentration of ethylparaben, butylparaben and propylparaben at 2.86, 2.55 and 2.67 h since last PCP use, respectively and twelve different types of PCPs were positively associated with at least one of these parabens. The bisphenol S concentration increased by 12.4% (95%CI: confidence interval: 5.9; 19.3) for each additional PCP application in the 12 to 24 time window and use of specific PCPs such as anti-stretchmarks cream, facial cleanser and shower gel. Associations varied by time window.Conclusion: Our study showed that PCP use was associated with a short-term increase in the urinary concentration of ethylparaben, butylparaben and propylparaben, but not methylparaben. This study also reported a positive association between the use of PCPs and the bisphenol S concentration, a finding that warrants further investigation in cohorts with repeated collection of urine samples and detailed information on PCP use

    Evaluating the effectiveness of Uganda’s Supranational TB Reference Laboratory quality management system training program

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    Abstract Background Achieving the targeted organizational goals through effective training can increase employee satisfaction. Since 2015, the Supranational Reference Laboratory Uganda (SRL Uganda) has trained National Tuberculosis Reference Laboratories (NTRLs) from 21 countries in a variety of areas that cover both technical and programmatic aspects pertinent to TB laboratories. The Laboratory Quality Management System (LQMS) under SRL coordinates actions intended to ensure sustained quality of the laboratory services offered by the National TB Reference Laboratories. In order for laboratory results to be helpful in a clinical or public health setting, they must be accurate, reliable, and timely. The LQMS course aims to provide learners with knowledge on how to attain and maintain this quality. Prior to this study, there was hardly any data available on the effectiveness of LQMS trainings provided by SRL Uganda; using Kirkpatrick model, which is popular among researchers for evaluating the efficacy of the training program, this paper seeks to establish the effectiveness of the LQMS training offered by the SRL Uganda. Method We evaluated the effectiveness of LQMS training within the Uganda’s SRL network for courses offered during the period 2017 and 2021 for participants from the Southern and East African sub-Saharan region. Results In 2017 and 2021, respectively, test results from 10/17 and 9/17 showed overall post-test scores above 80%. Of the 18 labs evaluated, 14 showed improvement; of these, 7 labs were from the Eastern region and the other 7 were from Southern Africa; one facility in this region also maintained its accreditation. In the post-evaluation assessment, attendees of the LQMS course gave feedback of strongly agree and agree variety. Conclusion More SRL Uganda network laboratories in the regions achieved a 5-star SLIPTA level rating and among these, 5 NTRLs got ISO 15189:2012 accredited by the end of 2021, while one maintained its accreditation status. This proves that the Laboratory Quality Management System training program was an effective tool in improving the quality of laboratory services, work practices, and processes

    Using methylome data to inform exposome-health association studies: An application to the identification of environmental drivers of child body mass index

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    Background: The exposome is defined as encompassing all environmental exposures one undergoes from conception onwards. Challenges of the application of this concept to environmental-health association studies include a possibly high false-positive rate. Objectives: We aimed to reduce the dimension of the exposome using information from DNA methylation as a way to more efficiently characterize the relation between exposome and child body mass index (BMI). Methods: Among 1,173 mother-child pairs from HELIX cohort, 216 exposures ("whole exposome") were characterized. BMI and DNA methylation from immune cells of peripheral blood were assessed in children at age 6-10 years. A priori reduction of the methylome to preselect BMI-relevant CpGs was performed using biological pathways. We then implemented a tailored Meet-in-the-Middle approach to identify from these CpGs candidate mediators in the exposome-BMI association, using univariate linear regression models corrected for multiple testing: this allowed to point out exposures most likely to be associated with BMI ("reduced exposome"). Associations of this reduced exposome with BMI were finally tested. The approach was compared to an agnostic exposome-wide association study (ExWAS) ignoring the methylome. Results: Among the 2284 preselected CpGs (0.6% of the assessed CpGs), 62 were associated with BMI. Four factors (3 postnatal and 1 prenatal) of the exposome were associated with at least one of these CpGs, among which postnatal blood level of copper and PFOS were directly associated with BMI, with respectively positive and negative estimated effects. The agnostic ExWAS identified 18 additional postnatal exposures, including many persistent pollutants, generally unexpectedly associated with decreased BMI. Discussion: Our approach incorporating a priori information identified fewer significant associations than an agnostic approach. We hypothesize that this smaller number corresponds to a higher specificity (and possibly lower sensitivity), compared to the agnostic approach. Indeed, the latter cannot distinguish causal relations from reverse causation, e.g. for persistent compounds stored in fat, whose circulating level is influenced by BMI.The study has received funding from the European Community’s Seventh Framework Programme (FP7/2007–2013) under grant agreement n° 308,333 – the HELIX project for data collection and analyses. The Norwegian Mother and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research, NIH/NIEHS (contract no N01-ES-75558), NIH/NINDS (grant n°0.1 UO1 NS 047537–01 and grant no.2 UO1 NS 047537-06A1). We also received support from Région Auvergne-Rhône-Alpes for collaborations with Catalunya. Dr. Chatzi was supported by NIH P30ES007048, R21ES029681, R01ES029944, R01ES030364, R21ES028903, and by Environmental Protection Agency RD-83544101
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