The persistent multidomain health effects of the early-life exposome

The environments experienced early in life can shape health across multiple body systems, yet most research on exposome health effects has focused on isolated exposure windows and health outcomes, limiting understanding of their combined and enduring effects. Leveraging the Human Early Life Exposome (HELIX) European cohort—the largest exposome dataset from the general pediatric population—we studied 586 mother-child pairs with nearly 200 prenatal and childhood exposures, including air pollutants, chemicals, lifestyle (diet, physical activity, and toxic habits), and neighborhood outdoors factors. Associations between these exposures and 11 outcomes across mental health, cardiometabolic, respiratory, and allergic domains, assessed in both childhood (6 to 11 years) and adolescence (12 to 18 years) were sought using an outcome-wide exposure-wide analysis. We identified a set of “master regulator” exposures, such as maternal smoking, indoor air pollution, endocrine-disrupting chemicals, and dietary and urban factors, that influenced multiple health domains, with effects persisting into adolescence. By providing an atlas of exposome-health associations across developmental stages—available as an open-access interactive resource—this work pinpoints critical early-life risks and offers a platform to guide prevention and policy.