The proposed UC Davis ECHO ReCHARGE Study will follow a cohort of children last seen at ages 2-5 years (‘baseline’) to determine environmental chemical and non-chemical stressors and resiliency factors that are associated with neurodevelopmental outcomes at ages 8-12 years (pre-adolescent) and 15-19 years (mid- to late adolescence). This project leverages the resources of the CHARGE (Childhood Autism Risks from Genes and Environment) Study, which, since 2003, has been enrolling three groups aged 2-5 years: children with autism spectrum disorder (ASD), children with other developmental delays (DD) and children from the general population with typical development (TD). These three groups, the ReCHARGE cohort, will be examined for the following outcomes of interest: attention deficit or hyperactivity symptoms; changes in cognitive or adaptive function; changes in severity or diagnosis; and symptoms of anxiety or depression. Pilot testing will take place in the UG3 phase, and in the UH3 phase, all will be examined either in pre-adolescence or mid- to late adolescence. The primary exposures of interest are pesticides, metals, air pollution, phthalates, nutrients, neighborhood characteristics, and family factors. Additionally, three mechanistic studies are proposed: an investigation of intergenerational epigenetic profiles; method development for metals analysis in dried blood spots; and sex specific associations of adrenal hormones with depressive symptoms. Approximately 1400 families are eligible for ReCHARGE, providing a robust sample for examination of main effects, interaction and mediation analyses. As part of the ECHO consortium, the ReCHARGE team will participate in the synthetic cohort combining children from multiple sites, and the cluster of studies focused on neurodevelopment in harmonizing protocols for the prospective UH3 phase and in seeking to analyze retrospective samples and data collaboratively, where feasible. During the UG3 phase, the ReCHARGE team will develop protocols, pilot test methods for recontacting and recruiting, for epigenetics in saliva vs. blood, and for implementation of the adrenal hormone study, including ways to increase compliance. Unique features of ReCHARGE include the contribution to understanding life course development in children with two different types of disabilities, and a novel model of adrenal hormone relationships with sex-specific affective disorders.

Public Health Relevance. Understanding the environmental contributors to neurodevelopment, as well as children’s health outcomes more broadly, is a particularly high priority for public health. The proposed ReCHARGE Study will shed light on chemical and nonchemical stressors in relation to ADHD, mood disorders, cognitive performance and other outcomes in children from three different diagnostic groups – autism, other developmental delay, and typical development – as they move into pre-adolescence and mid to late adolescence. It will lay the basis for interventions to improve the lives of all children.