PROJECT SUMMARY / ABSTRACT Early exposures in critical developmental windows around fertilization, implantation, and during pregnancy can have long-term impact on health, development, and disease in children. A comprehensive assessment of early exposures requires a multidimensional assessment of the exposome, including community-level environmental factors (including air pollution), chemical exposures (including endocrine disruptors), the microbiome (including commensals and infectious agents with associated immune responses), and the genome and its responses to the environment (including the inherited epigenome, genomic expression, and the proteome). We are currently re-enrolling a pediatric cohort from two birth cohorts enrolled peri-conceptionally/prenatally, 1) the Utah participants in the National Children’s Study, and 2) participants in the Home Observation of Peri-conceptional Exposures (HOPE) study, into the Early Life Exposures and Child Trajectories (ELECT) cohort. We are also enrolling biological parents and up to one biological sibling child. In the UG3 phase (the first two years), we focus on completing re-enrollment of the entire cohort, and also on innovative methods for assessment of a spectrum of known and emerging exposures during the key early windows of the peri-conceptional time and early pregnancy. Exposures we assess will include the microbiome, medications, infections, pan-viral antibody assessment, air pollutants (especially particulate pollution (PM2.5), also nitrogen oxides and ozone), endocrine disrupting chemicals (particularly bisphenol-A (BPA) and phthalates), and hypomineralization of dental enamel as a marker for early endocrine disrupting exposure. We will also conduct a preliminary assessment of some health impacts. In UH3 phase, we will focus on the association of these exposures with subsequent outcomes in two focus areas: growth (including insulin resistance and childhood obesity) and respiratory health (including respiratory infections and asthma). We will work completely collaboratively with the ECHO national synthetic cohort to integrate UCP-ELECT into that cohort. We will contribute to the design of the core measures for the synthetic ECHO cohort and implement these within UCP-ELECT. Taken together, this proposal focuses throughout both UG3 and UH3 on novel assessments for exposures that can be translated to other settings of the ECHO synthetic cohort in a feasible and cost-effective manner. We are focused particularly on assessments that can be applied retrospectively in other cohorts to assess very early exposures (peri- conception and early pregnancy). Thus, we will contribute to the ECHO cohort 1) a population-based, pediatric cohort (950 children from 500 families) with extant and new early biospecimens and assessments, and 2) scientific validation of critical multidimensional exposome measurements from preconception through gestation and early childhood. These methods will then be available to asses...