PROJECT SUMMARY: The Columbia Center for Children’s Environmental Health (CCCEH) has provided an exemplary record of solution-oriented children’s environmental health research. From gestation through young adulthood, CCCEH has successfully followed children to address research questions relevant to the Northern Manhattan and South Bronx communities and beyond, for whom many complex childhood diseases are highly prevalent. CCCEH has prioritized enrollment of under-represented, at-risk Black and/or Hispanic pregnant individuals. We have documented effects of physical, chemical, and social exposures on airway diseases such as childhood asthma, and neurodevelopmental disorders such as Attention Deficit Hyperactivity Disorder (ADHD), two highly prevalent and frequently comorbid conditions with a large individual and societal burden. For the second phase of the Environmental Influences on Child Health Outcomes (ECHO-II) consortium, in Aim 1 we will use ECHO-wide core data elements to examine common patterns of prenatal physical, chemical, and social exposures that associate with childhood asthma and ADHD to understand their contribution to both disorders and their well- established co-morbidity, which requires a large population such as ECHO to study. The ECHO cohort provides a unique opportunity to examine robustly if prenatal exposure patterns contribute to asthma/ADHD comorbidity via shared or distinct causal pathways. This science will address current gaps in knowledge that will improve strategies for prevention and treatment by: 1) raising risk-awareness; 2) increasing referrals for assessment of comorbid disorders; and 3) allowing for earlier intervention. In Aim 2, we will contribute to the development of specialized protocols by proposing to measure biomarkers of prenatal chemical exposure using a novel bioassay and adding annual measures of asthma and ADHD and their phenotypes to identify patterns of prenatal physical, chemical, and social exposures that associate with incident asthma and ADHD as well as their phenotypes that may have distinct etiologies. This more granular characterization of exposure and heterogenous outcomes will enable more precise strategies for early identification and prevention along with primary and tertiary interventions for asthma and ADHD. In Aim 3, we will implement the ECHO Cohort Protocol with high fidelity, maximizing the retention of existing ECHO participants and supporting the continued recruitment of new pregnant and preconception participants while emphasizing inclusive subject representation. In Exploratory Aim 4, we will evaluate the role of chemical exposures during the preconception period on pregnancy loss and early indicators of respiratory and neurodevelopmental health. Finally, the CCCEH site proposes a plan for enhancing diverse perspectives that will be implemented while conducting all four aims. Altogether, this proposal is intended to make a large scientific impact on children’s environmental h...