Associations of prenatal metal exposures with autism-related outcomes in the ECHO cohort

Background: Metal exposures adversely impact prenatal neurodevelopment; however, their associations with child autism spectrum disorder (ASD) remain unclear. Methods: In the Environmental Influences on Child Health Outcomes Cohort, we analyzed prenatal blood (N = 479) and urinary (N = 482) metal concentrations in relation to Social Responsiveness Scale—Second Edition (SRS-2) total T-scores, SRS-2 subscale T-scores, and ASD diagnosis. Associations were examined using linear and logistic regression for individual metals and Bayesian Kernel Machine Regression for mixtures, adjusting for covariates. Results: Interquartile range increases in maternal blood lead and mercury were associated with higher SRS-2 total T-scores (lead: β = 0.11, 95% confidence interval [CI] = 0.03, 0.18; mercury: β = 0.19, 95% CI = 0.01, 0.37), and maternal blood cadmium was associated with higher odds of ASD diagnosis (OR = 2.42, 95% CI = 1.16, 5.03). Bayesian Kernel Machine Regression revealed joint effects of blood metal mixtures (arsenic, cadmium, mercury, and lead) on social awareness and cognition. Blood cadmium correlated with social awareness in females (raw score: β = 0.85, 95% CI = 0.09, 1.61) versus males ( p -interaction = 0.02). Urinary barium correlated with social motivation in females (raw score: β = 0.273, 95% CI = 0.067, 0.478) versus males ( p -interaction = 0.05). Conclusions: Future research should prioritize metal speciation, larger samples, and mechanistic studies to clarify sex-specific pathways.