Work

Neighborhood Exposome at Birth and Trajectories of Epigenetic Age Acceleration Across Childhood

Year: 2026

Type: preprint

Abstract: 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. Key Points Question Is the neighborhood exposome at birth associated with trajectories of epigenetic age acceleration (EAA) from early childhood through adolescence? Findings In this cohort study of 570 children, birth into neighborhoods with high residential instability and single-person households, and highway proximity were associated with greater odds of increasing EAA trajectories across ages 3, 8, and 13 (Wu clock). Traffic density, residential instability, and proportion of residents living alone were the most prominent characteristics. Meaning Adverse neighborhood social and environmental conditions in early life may be associated with increasing Wu EAA across childhood, suggesting potential targets for place-based prevention if replicated.

Source: medRxiv

DOI: 10.64898/2026.08.21.26361042