SUMMARY The Navajo Birth Cohort Study (NBCS) is the first large-scale, well characterized prospective cohort study to assess the relationships between environmental exposures, birth outcomes, and child development in a tribal population. Representation of the Navajo population in the National ECHO cohort will contribute significantly to the understanding of risks to Indigenous populations through comparison of exposures and outcomes with other Indigenous populations and minority populations in ECHO, enhancing the understanding of the contributions of cultures with respect to both similarities and differences. Through participation in ECHO, the NBCS will build on the unique combination of characteristics to understand contributions of sociodemographic, nutritional, cultural, and exposure variables to health outcomes as well as to positive child health. We will ask research questions that take advantage of the size and diversity of the broader ECHO Cohorts to address key questions about how variables such as income, education, and rurality combine with exposure variables to contribute to health outcomes, including resiliency. We will assess language development, learning, social communication, and neurodevelopmental diagnosis over time to understand developmental trajectories and to ask how early-life experiences and exposures assessed through ECHO may influence these trajectories. We also ask questions about how the COVID-19 infection and the pandemic may have affected developmental trajectories, including potential long-covid effects. Over the course of the next 7 years in ECHO Cycle 2, we propose to contribute data on a cumulative total of 5300 participants, inclusive of pregnancies, offspring, conceiving partners, and current participants reconsented into the updated protocol. Our recruiting team has a deep understanding of the culture and life circumstances that exist for our study participants and employ multiple strategies to overcome existing barriers to participant recruitment, reconsent and retention. We propose to recruit a minimum of 30 couples per year into the preconception pilot to address how exposures during preconception to mixed metals or other toxicants of interest across ECHO, affect fertility, birth outcomes and developmental trajectories of offspring. Inclusion of NBCS in ECHO provides an opportunity to assess child health in a tribal population with diverse cultural practices and sociodemographics who experience significant exposures to toxicants. ECHO is one of the only sources where inclusion, even at a population- representative percentage, will allow for evaluation of child development relative to the US population overall. NBCS contributes to the diversity of ECHO through inclusion of a group traditionally underrepresented in population studies of this magnitude, yet adversely affected by exposures in all categories specified in ECHO, with outcomes of clinical concern in all key outcomes addressed through the ECHO core ...