Gestational exposure to endocrine-disrupting chemicals and reciprocal social, repetitive, and stereotypic behaviors in 4- and 5-year-old children: the HOME study

Abstract

Background: Endocrine-disrupting chemicals (EDCs) may be involved in the etiology of autism spectrum disorders, but identifying relevant chemicals within mixtures of EDCs is difficult.

Objective: Our goal was to identify gestational EDC exposures associated with autistic behaviors.

Methods: We measured the concentrations of 8 phthalate metabolites, bisphenol A, 25 polychlorinated biphenyls (PCBs), 6 organochlorine pesticides, 8 brominated flame retardants, and 4 perfluoroalkyl substances in blood or urine samples from 175 pregnant women in the HOME (Health Outcomes and Measures of the Environment) Study (Cincinnati, OH). When children were 4 and 5 years old, mothers completed the Social Responsiveness Scale (SRS), a measure of autistic behaviors. We examined confounder-adjusted associations between 52 EDCs and SRS scores using a two-stage hierarchical analysis to account for repeated measures and confounding by correlated EDCs.

Results: Most of the EDCs were associated with negligible absolute differences in SRS scores (≤ 1.5). Each 2-SD increase in serum concentrations of polybrominated diphenyl ether-28 (PBDE-28) (β = 2.5; 95% CI: -0.6, 5.6) or trans-nonachlor (β = 4.1; 95% CI: 0.8-7.3) was associated with more autistic behaviors. In contrast, fewer autistic behaviors were observed among children born to women with detectable versus nondetectable concentrations of PCB-178 (β = -3.0; 95% CI: -6.3, 0.2), β-hexachlorocyclohexane (β = -3.3; 95% CI: -6.1, -0.5), or PBDE-85 (β = -3.2; 95% CI: -5.9, -0.5). Increasing perfluorooctanoate (PFOA) concentrations were also associated with fewer autistic behaviors (β = -2.0; 95% CI: -4.4, 0.4).

Conclusions: Some EDCs were associated with autistic behaviors in this cohort, but our modest sample size precludes us from dismissing chemicals with null associations. PFOA, β-hexachlorocyclohexane, PCB-178, PBDE-28, PBDE-85, and trans-nonachlor deserve additional scrutiny as factors that may be associated with childhood autistic behaviors.

Figure 1

Associations between maternal gestational urine or serum EDC concentrations and SRS total T-scores in 4- and 5-year-old Cincinnati children using a semi-Bayesian model (n = 175). PCB-66, PCB‑101, PCB-157, PCB-167, PCB-172, PCB-177, PCB-178, PCB-195, PCB-209, β-HCH, DDT, PBDE-85, PBDE-154, and PBDE‑183 are coded as detected vs. nondetectable. The displayed betas are the change in SRS scores among children born to women with detectable vs. nondetectable levels of these chemicals. All other chemicals were treated as continuous log₁₀-transformed variables that are divided by two times their standard deviation to put them on a comparable scale to the dichotomous variables. Adjusted for demographic factors for the covariate-adjusted semi-Bayesian model (see Table 2), as well as depressive symptoms during pregnancy (continuous), HOME score (continuous), and gestational serum cotinine concentration (continuous log10 transformed). The residual variance (τ²) of the semi-Bayesian model was set to 26.03 (20-point range). The exchangeability matrix is contains an intercept and indicator (0/1) variables for OCs, PCBs, BFRs, PFASs, DEHP metabolites, DBP metabolites, and persistent vs. nonpersistent chemicals. Whiskers indicate 95% CIs.

Figure 2

Confounder-adjusted associations between maternal gestational urinary or serum EDC concentrations and SRS total T-scores in 4- and 5-year-old Cincinnati children, stratified by child sex (n = 175). All displayed betas are the change in child SRS scores with a 2‑SD increase in log₁₀-transformed maternal chemical concentration. Adjusted for demographic factors (see Table 2) as well as depressive symptoms during pregnancy (continuous), HOME score (continuous), and gestational serum cotinine concentration (continuous log₁₀ transformed). Whiskers indicate 95% CIs. Only associations with significant chemical × sex interactions are displayed (p < 0.10).