ABSTRACT Black Americans and other racial and ethnic minorities experience higher levels of psychosocial stress and are exposed to unique stressors, such as discrimination and structural racism. Prenatal psychosocial stress increases risk for a range of adverse maternal, perinatal and child neurodevelopmental outcomes. However, nationally representative samples with prospective data on maternal report of prenatal stress and discrimination and verified perinatal and child health outcomes are lacking, as are investigations that consider risk and protective pathways that reflect solution-oriented research. The ECHO Cohort is ideal for advancing solution-oriented science around maternal psychosocial stress exposures, perinatal risk pathways, and child health outcomes as the protocol includes measures of prenatal stress and experiences of discrimination, social support and cohesion, prenatal health behaviors (diet, physical activity, sleep, substance use), pregnancy complications and birth outcomes, and child health outcomes for a socio-demographically heterogenous, national sample. Geocoding efforts also enable the consideration of area level measures of structural racism, allowing for multi-level, multi-domain analyses in line with the NIMHD research framework for investigating health disparities. We seek to extend follow-up of our Atlanta ECHO Cohort participants under the ECHO Protocol and to participate in solution-oriented team science. Enrolled children are now 2 to 7 years old and will be followed with annual visits consistent with the ECHO Protocol, with a focus on child neurodevelopment as a specialized outcome area. The unique contributions of our Cohort Study site include our capacity to follow hard-to-reach racial and ethnic minority families (as our cohort is wholly composed of Black American families, 75% of whom are of lower socioeconomic status); our geographic location in a major metropolitan area in the US Southeast that experiences unique regional and area-level stressors (e.g., racialized segregation); and our multi-disciplinary team of psychosocial, clinical, and omic investigators with expertise in (personalized) exposure assessment, maternal stress, perinatal and birth outcomes, and child neurodevelopment. Given our team’s expertise, and preliminary data that supports an association between stress, omics pathways, and neurodevelopment, we plan to lead test novel hypotheses about how prenatal stress (including racial discrimination) leads to perturbations in the metabolome, epigenome and microbiome, and how these biological perturbations, in turn, predict child neurodevelopment. We will also test the role of racial discrimination experiences in children’s health outcomes in the ECHO cohort, as well as modifiable mediators (maternal prenatal sleep quality and postpartum depression) and moderators (social support) which will inform potential intervention strategies designed to improve children’s health outcomes.