PROJECT SUMMARY Consistent with the Developmental Origins of Health and Disease theory, prenatal stress can have enduring effects on offspring health and may be a major pathway through which stress-related health problems are transmitted across generations. This transmission of risk disproportionately impacts marginalized groups, such as people of color and families living in under-resourced communities who experience lifelong inequities in social determinants of health (e.g., discrimination, access to healthcare, neighborhood violence). Strengths- based models are lacking in prenatal research, and there is limited understanding of resilience-promoting factors that may buffer the impact of chronic stress exposure on maternal stress responsive systems and placental function. Research conducted via our current ECHO award has contributed to evidence supporting the preconception period as an important window of vulnerability to the effects of stressors on maternal and child health. In this renewal, we leverage ECHO data to examine the extent to which nutritional status and social support/connectedness attenuate the negative effects of stressors on child neurodevelopment across racially and socioeconomically diverse groups. Our ECHO Cohort will continue to enroll participants from the ongoing, longitudinal Pittsburgh Girls Study (PGS), an urban-population sample of 2,450 women (now ages 26-29) who have been followed since childhood. PGS participants (n=568, 69% Black, 27% White, 4% multi-racial) have been enrolled into the ECHO Study as they become pregnant; a further 609 individuals will be recruited in the renewal period, yielding a total Cohort of 1,177. Extensive preconception data are available from the PGS for all existing and future ECHO participants. Guided by our Community Stakeholder Partner Board, we will implement the ECHO Protocol with high fidelity, and propose innovative, specialized measures of prenatal stress exposure (i.e., maternal hypothalamic-pituitary-adrenal axis functioning and placental CRH) and child executive function and stress reactivity that can be readily deployed across ECHO Cohort sites. Thus, in response to RFA-OD-22- 018, we will advance the development, production, and dissemination of ECHO Cohort solution-oriented collaborative science with the following Specific Aims: 1) Elucidate health and contextual factors that attenuate the impact of prenatal stress exposure on child neurodevelopment; 2) Examine associations between stress exposure, prenatal stress reactivity and offspring neurodevelopment; 3) Maximize participant retention, ensure sample diversity and implement the ECHO protocol with high fidelity; and 4) Explore the timing and cumulative effects of stress exposure on child health outcome. Our diverse, multidisciplinary team, representing wide ranging identities, backgrounds and perspectives, has expertise in every aspect of the proposed study and is highly qualified to lead collaborative cohort science in ...