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 $\text{women}>18\text{years}$ 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 ($\text{SD}=6.1$). 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 (${\beta }_{\text{MBP}}=1.0$; 95% CI: 0.4, 1.6; $n=252$) compared with girls (${\beta }_{\text{MBP}}=0.1$; 95% CI: $-0.6$, 0.7; $n=258$) and among children who had lower prenatal folic acid supplementation ($<400\mu g/d$) (${\beta }_{\text{MBP}}=1.3$; 95% CI: 0.4, 2.3; $n=59$) compared with those who had adequate folic acid supplementation ($\ge 400\mu g/d$) (${\beta }_{\text{MBP}}=0.4$; 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.