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Gestational Exposures to Phthalates and Folic Acid, and Autistic Traits in Canadian Children.

ABSTRACT: BACKGROUND:The etiology of autism spectrum disorder is poorly understood. Few studies have investigated the link between endocrine-disrupting chemicals and autistic traits. We examined the relationship between gestational phthalates and autistic traits in 3- to 4-y-old Canadian children. We also investigated potential effect modification by sex and folic acid supplementation. METHODS:We enrolled 2,001 women>18?years of age during the first trimester of pregnancy between 2008 and 2011 from 10 cities in Canada. At 3-4 years of age, 610 children underwent neuropsychological assessments including the Social Responsiveness Scale-II (SRS-2) as a measure of autistic traits and social impairment. We measured 11 phthalate metabolites in maternal first trimester urine samples and assessed folic acid supplementation from reported intakes. We estimated covariate-adjusted differences in SRS-2 T-scores with a doubling in phthalate concentrations in 510 children with complete data. RESULTS:Mean total SRS T-score was 45.3 (SD=6.1). Children with higher gestational exposure to mono-n-butyl (MBP) and mono-3-carboxypropyl (MCPP) concentrations exhibited significantly higher total SRS T-scores, indicating greater overall social impairment, as well as higher scores on subdomains, indicating deficits in social cognition, social communication, social motivation, and restricted interests/repetitive behaviors. A doubling in MBP or MCPP concentrations was associated with 0.6 (95% CI: 0.1, 1.0) and 0.5 (95% CI: 0.1, 0.8) higher total SRS T-scores. Associations were consistently and significantly stronger in boys (?MBP=1.0; 95% CI: 0.4, 1.6; n=252) compared with girls (?MBP=0.1; 95% CI: -0.6, 0.7; n=258) and among children who had lower prenatal folic acid supplementation (<400?g/d) (?MBP=1.3; 95% CI: 0.4, 2.3; n=59) compared with those who had adequate folic acid supplementation (?400?g/d) (?MBP=0.4; 95% CI: -0.1, 0.8; n=451). CONCLUSIONS:Higher gestational concentrations of some phthalate metabolites were associated with higher scores of autistic traits as measured by the SRS-2 in boys, but not girls; these small size effects were mitigated by first trimester-of-pregnancy folic acid supplementation. https://doi.org/10.1289/EHP5621.

SUBMITTER: Oulhote Y

PROVIDER: S-EPMC7064316 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Gestational Exposures to Phthalates and Folic Acid, and Autistic Traits in Canadian Children.

Oulhote Youssef Y Lanphear Bruce B Braun Joseph M JM Webster Glenys M GM Arbuckle Tye E TE Etzel Taylor T Forget-Dubois Nadine N Seguin Jean R JR Bouchard Maryse F MF MacFarlane Amanda A Ouellet Emmanuel E Fraser William W Muckle Gina G

Environmental health perspectives 20200219 2

<h4>Background</h4>The etiology of autism spectrum disorder is poorly understood. Few studies have investigated the link between endocrine-disrupting chemicals and autistic traits. We examined the relationship between gestational phthalates and autistic traits in 3- to 4-y-old Canadian children. We also investigated potential effect modification by sex and folic acid supplementation.<h4>Methods</h4>We enrolled 2,001 women>18 years of age during the first trimester of pregnancy between 2008 and 2 ...[more]

PMID: 32073305

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Project description:Importance:Strategies to prevent autism in children exposed to antiepileptic drugs (AEDs) during pregnancy are important. Objective:To explore whether folic acid supplementation and folate status in pregnancy are associated with reduced risk of autistic traits owing to in utero AED exposure. Design, Setting, and Participants:The population-based, prospective Norwegian Mother and Child Cohort Study approached Norwegian-speaking women attending routine ultrasonographic examinations from June 1999 through December 31, 2008 (163?844 of 277?702 women refused). No exclusion criteria were applied beyond language. Questionnaires during and after pregnancy, analysis of blood samples, and linkage to the Medical Birth Registry of Norway were performed. Children aged 18 to 36 months of women with available information on use of AEDs and of folic acid supplementation (n?=?104?946) were included in the analysis from March 1, 2016, through June 13, 2017. Exposures:Maternal folic acid supplementation 4 weeks before to 12 weeks after conception. Plasma folate concentration was analyzed at gestational weeks 17 to 19. Main Outcomes and Measures:Autistic traits were evaluated using the Modified Checklist for Autism in Toddlers and Social Communication Questionnaire. Odds ratios (ORs) for autistic traits in children by maternal use vs nonuse of folic acid supplements were adjusted for maternal health and socioeconomic factors. Folate concentrations and folic acid doses were associated with the degree of autistic traits. Results:The overall mean (SD) age of the 104?946 mothers of participating children was 29.8 (4.6) years, with complete information available for analysis in 103 868. Mean (SD) age of women with epilepsy who received AED treatment was 29.4 (4.9); women with epilepsy who did not receive AED treatment, 29.1 (4.9); and without epilepsy, 29.8 (4.6) years. In the 335 children exposed to AEDs, the risk for autistic traits was significantly higher at 18 months of age (adjusted OR [AOR], 5.9; 95% CI, 2.2-15.8) and 36 months of age (AOR, 7.9; 95% CI, 2.5-24.9) when their mothers had not used folic acid supplements compared with children of mothers who had used supplements. Among women without epilepsy, the corresponding risks were lower at 18 months of age (AOR, 1.3; 95% CI, 1.2-1.4) and 36 months of age (AOR, 1.7; 95% CI, 1.5-1.9); among the 389 children of women with untreated epilepsy, the corresponding risks were not significant at 18 months of age (AOR, 1.0; 95% CI, 0.4-3.0) and 36 months of age (AOR, 2.5; 95% CI, 0.4-16.6). Degree of autistic traits was inversely associated with maternal plasma folate concentrations (??=?-0.3; P?=?.03) and folic acid doses (??=?-0.5; P?<?.001). Concentrations of AEDs were not associated with the degree of autistic traits. Conclusions and Relevance:Risk of autistic traits in children exposed to AEDs in utero may be mitigated by periconceptional folic acid supplementation and folate status. Fertile women using AEDs should take folic acid supplements continuously.

Project description:BackgroundEarly-life phthalate exposures may adversely influence neurodevelopment by disrupting thyroid hormone homeostasis, altering brain lipid metabolism, or reducing gonadal hormone concentrations. Previous literature examining gestational phthalate exposure and child behavior were inconclusive and few prospective studies have examined childhood phthalate exposure, particularly phthalate mixtures. We investigated whether gestational and childhood phthalate exposures were associated with child behavior.MethodsWe used data from 314 mother-child pairs in the HOME Study, a longitudinal pregnancy and birth cohort that enrolled pregnant women from Cincinnati, Ohio. We quantified urinary concentrations of 11 phthalate metabolites in samples collected twice during gestation from women and six times from their children when they were ages 1, 2, 3, 4, 5, and 8 years. We assessed children's behavior at ages 2, 3, 4, 5, and 8 years using the Behavioral Assessment System for Children-2. Using linear mixed models, we estimated covariate-adjusted associations of measurement-error-corrected gestational and childhood phthalate metabolite concentrations (per interquartile range increase) with repeated child behavior assessments. We used Weighted Quantile Sum (WQS) regression to estimate the association of phthalate mixtures with child behavior.ResultsGestational mono(3-carboxypropyl) phthalate (MCPP) concentrations were associated with more problem behaviors (internalizing: β = 0.9, 95% confidence interval [CI] = -0.1, 1.9; externalizing: β = 1.0, 95%CI = -0.1, 2.0; behavioral symptoms index [BSI]: β = 1.1, 95%CI = 0.1, 2.1). Higher childhood monobenzyl phthalate (MBzP) (β = 1.4; 95%CI = 0.0, 2.7), monocarboxynonyl phthalate (MCNP) (β = 3.2; 95%CI = 1.6, 4.8), monocarboxyoctyl phthalate (MCOP) (β = 0.9; 95%CI = 0.0, 1.7), MCPP (β = 1.8; 95%CI = 0.2, 3.5), and monoethyl phthalate (MEP) (β = 1.6; 95%CI = 0.1, 3.1) concentrations were associated with higher BSI composite scores. Consistent with this, the weighted childhood phthalate index was associated with more problem behaviors (internalizing: β = 1.5, 95%CI = -0.2, 3.1; externalizing: β = 1.7, 95%CI = 0.1, 3.5; BSI: β = 1.7, 95%CI = 0.2, 3.2); MBzP, MCNP, and MEP largely contributed to these associations.ConclusionOur findings suggest that childhood exposure to phthalate mixtures may be associated with children's problem behaviors.

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Gestational Exposures to Phthalates and Folic Acid, and Autistic Traits in Canadian Children.

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Gestational Exposures to Phthalates and Folic Acid, and Autistic Traits in Canadian Children.

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