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.
Pi-I. D. Lin, Andrés Cárdenas, K. Lyall et al.· Environmental Epidemiology· 0 citations
Importance: Epigenetic age acceleration (EAA) has been linked to increased disease risk in adults, yet its developmental trajectories and early-life neighborhood determinants remain poorly understood. Objective: To examine associations between the neighborhood exposome at birth and EAA trajectories from early childhood through adolescence. Design, Setting, and Participants: Longitudinal cohort study using data from Project Viva, a pre-birth cohort that enrolled pregnant women in eastern Massachusetts (1999-2002). Participants included 570 children with available peripheral blood DNA methylation data, complete neighborhood characteristics, and complete covariates. Data were analyzed from 2024 to 2026. Exposures: Neighborhood exposome profiles at birth derived from 22 census tract-level characteristics across four domains (area deprivation, social fragmentation, population density, and environmental quality) using self-organizing maps. Main Outcomes and Measures: EAA was calculated at ages 3 (n=84), 8 (n=301), and 13 (n=434) years using Horvath, Skin & Blood, and Wu epigenetic clocks. Trajectories were identified using latent class linear mixed models. Associations between neighborhood profiles and EAA trajectories were estimated using multinomial mixed models. Results: Among 570 children (mean [SD] age at early childhood, 3.2 [0.4] years; 265 [46.5%] female), three EAA trajectory groups (stable, increasing, and decreasing for the Horvath and Skin & Blood clocks or low-baseline for the Wu clock) and three neighborhood profiles were identified. Compared with Profile 1 (suburban, lowest adverse exposures; n=278), children born into Profile 2 (urban, high residential instability and single-person households, and highway proximity; n=168) had greater odds of increasing EAA for Wu clock (aOR, 1.67; 95% CI, 1.03-2.69). Profile 3 (urban, high socioeconomic deprivation; n=124) showed no significant associations. Conclusions and Relevance: In this longitudinal cohort study, birth into neighborhoods characterized by high residential instability and single- person households, and highway proximity was associated with increasing Wu EAA trajectories across childhood. These findings suggest that early-life neighborhood conditions, encompassing both social and physical environmental factors, may represent targets for interventions aimed at reducing long-term disease risk. Further research is needed to clarify the implications of these findings for later health and prevention.
Q. Yuan, A. Bozack, V. Paquin et al.· medRxiv· 0 citations
