PROJECT SUMMARY Despite improvements in access and quality of health care in the United States (US), children from socioeconomically disadvantaged families and / or of minority race have an elevated risk for impaired cognitive and social-emotional development. Indeed, children in poverty are 40% more likely to experience developmental delays relative to children not in poverty. Poverty engenders disproportionate exposure to adversity including parental/child psychosocial stressors (such as, exposure to violence, frequent relocation) and psychological distress (such as, maternal depression) that contribute to impaired childhood development. However, negative effects may be mitigated in the presence of protective factors. While measures of maternal adversity and protective factors have been evaluated in association with child development, the combined effects of these opposing forces and the potentially related and critical role of epigenetic programming have not been determined. In particular, at sensitive periods across the life-course when their effects have the strongest impact. Our preliminary data suggest that maternal adversity during two sensitive time periods (prenatally and early life) epigenetically program infant response systems, thereby altering child development. Our overall hypothesis is that maternal adversity and protective factors (i.e., maternal psychosocial experience) faced across the life- course contribute to offspring cognitive and social-emotional developmental disparities through DNA methylation (DNAm) of genes in multiple biologic pathways. This study combines retrospective assessment and prospective data collection on 375 mother-infant dyads captured in 5 study visits spanning pregnancy through 18 months postnatal. The specific aims of the proposal are 1) determine the association between the life-course maternal psychosocial experience and the change in infant DNAm during the first year of life, a sensitive developmental window, 2) characterize the association between postnatal maternal psychosocial experiences in the infant’s first year of life and infant DNAm at one year, and 3) determine the impact of DNAm at two time points (1 month and 12 months) of infant development across the first 18 months. This research will be conducted within a large, regional home visiting program, uniquely positioning us to translate findings through precision home visiting and additional strategies aimed at reducing early developmental health disparities.