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

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DOI

https://doi.org/10.1289/EHP5621

Language of the publication
English
Date
2020-02-19
Type
Article
Author(s)
  • Oulhote, Youssef
  • Lanphear, Bruce
  • Braun, Joseph M.
  • Webster, Glenys M.
  • Arbuckle, Tye E.
  • Etzel, Taylor
  • Forget-Dubois, Nadine
  • Seguin, Jean R.
  • Bouchard, Maryse F.
  • MacFarlane, Amanda
  • Ouellet, Emmanuel
  • Fraser, William
  • Muckle, Gina
Publisher
National Institute of Environmental Health Sciences

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 (βMBP=1.0; 95% CI: 0.4, 1.6; n=252) compared with girls (βMBP=0.1; 95% CI: −0.6, 0.7; n=258) and among children who had lower prenatal folic acid supplementation (<400μg/d) (βMBP=1.3; 95% CI: 0.4, 2.3; n=59) compared with those who had adequate folic acid supplementation (≥400μg/d) (βMBP=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.

Plain language summary

"Health Canada helps to protect the health of Canadians by assessing and managing the risks associated with exposure to environmental chemicals. Phthalates are a group of chemicals used in plastics to soften and increase flexibility. They can also be used in a number of products including cosmetics, fabrics, paints, and drugs. Some phthalates are commonly measured in urine of Canadians, while others are less commonly measured. Approximately 1.5% of Canadian children have been diagnosed with autism spectrum disorder and the causes of this condition are not clear. There may be an association between prenatal exposure to elevated levels of some chemicals and autistic characteristics. This study examined the association between phthalate concentrations in urine of pregnant women from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study and characteristics of autism in their 3-4 year old children. Information on dietary supplements containing folic acid was obtained by questionnaire during the pregnancy. Children who had higher prenatal exposure to mono-n-butyl phthalate (MBP) and mono-3-carboxypropyl phthalate (MCPP) had poorer scores of social cognition, communication, and motivation, and restricted interests/repetitive behaviors, especially in boys. The associations of MCPP and di-2-ethylhexyl phthalate (DEHP) with these scores were stronger among children born to mothers who had low prenatal folate supplementation (<400 µg/day). Higher prenatal exposure to some phthalates was associated with social impairments in boys, but not girls; the associations were less if the woman had adequate folate supplementation. These results will add to the body of knowledge on potential risk factors for autistic characteristics."

Subject

  • Health,
  • Health and safety

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