Gestational exposures to mixtures of multiple chemical classes and autism spectrum disorder in the MARBLES study

Document Type

Journal Article

Publication Date

4-16-2025

Journal

Environmental research

DOI

10.1016/j.envres.2025.121646

Keywords

autism; chemical exposure; gestational exposure; interaction; mixture

Abstract

BACKGROUND: Previous epidemiologic studies on gestational chemical exposures and autism spectrum disorder (ASD) often lack analysis of chemical mixtures or are limited to investigating certain chemical classes. OBJECTIVE: We examined the impact of multi-class chemical mixtures on ASD risk, using data from the MARBLES (Markers of Autism Risks in Babies-Learning Early Signs) cohort. METHODS: Children were clinically assessed at age 3 and classified as ASD, typical development (TD), or non-TD with other neurodevelopmental concerns. In blood or urine from 105 pregnant mothers, we quantified 42 biomarkers across 5 chemical classes: per- and polyfluoroalkyl substances (PFAS), parabens, phenols, phthalates, and organophosphate esters (OPEs). We only analyzed 30 biomarkers detected in >50% of the sample. After identifying clusters with similar chemical profiles via hierarchical clustering, we applied linear discriminant analysis (LDA) to compute LDA exposure summary scores. In covariate-adjusted models, we used LDA scores to assess co-adjusted, multipollutant associations (relative risk [RR]) with ASD or non-TD, via quasi-Poisson regression. We further examined overall mixture effect and chemical interactions with Bayesian kernel machine regression. RESULTS: We identified four distinct clusters: PFAS (Cluster 1), OPEs (Cluster 2), parabens and triclosan (Cluster 3), and phthalates and bisphenol A (Cluster 4). Relative to TD, LDA scores for each cluster were associated with increased risk of ASD (RR [95% CI]: 1.14 [1.03, 1.25], 1.12 [1.01, 1.24], 1.17 [1.07, 1.29], 1.17 [1.07, 1.28] for Cluster 1-4, respectively), whereas clusters 2 and 4 were associated with non-TD (1.07 [1.07, 1.14] and 1.12 [1.05, 1.19], respectively). Cumulative exposure across the four clusters was linked to increased risk of both ASD and non-TD. Potential interactions within and between clusters were observed. CONCLUSION: This study shows that considering multiple chemical classes resulted in stronger associations with ASD and non-TD risk, compared to when investigated separately in our previous studies.

Department

Environmental and Occupational Health

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