PROJECT SUMMARY/ABSTRACT Preterm birth and the hospitalization of infants in the neonatal intensive care unit (NICU) are well-documented as stressful events for mothers. Although maternal milk is critically important to promote optimal health and neurodevelopment for preterm infants, the effects of maternal postnatal stress on maternal lactation and feeding outcomes and milk composition have not been systematically examined. The goal of this proposed Pathway to Independence Award is to pair a detailed examination of lactation and feeding outcomes for preterm infants in the NICU with a biological systems approach to understanding human milk to examine the hypothesis that maternal stress is associated with feeding outcomes and markers of impaired neurodevelopment for preterm infants and alters human milk and infant gut profiles in ways that affect preterm neurodevelopment. The proposed research directly aligns with the Eunice Kennedy Shriver National Institute of Child Health and Human Development’s scientific priorities to reduce the incidence of neurodevelopmental disorders, optimize outcomes for preterm infants by understanding nutrition/feeding and the microbiome, and to understand human milk composition in relationship with maternal characteristics. During the K99 phase, measurement of perceived, biological, and known maternal stressors in the NICU will be conducted and assessed in relation to maternal lactation and feeding outcomes (milk production, mothers’ own milk vs donor milk vs preterm formula) (Aim 1). Infants will also undergo neurodevelopmental testing via electroencephalogram before NICU discharge and at 4 months corrected age to assess the relationship between maternal stress and preterm neurodevelopmental outcomes (Aim 2). Career development activities in the K99 phase, including training in stress physiology and infant neurodevelopment, developing expertise in lactation/feeding outcomes for preterm infants in the NICU, and learning techniques for assessing human milk and infant gut composition data and their interpretation will take place in the excellent research environment at the University of Minnesota School of Public Health Division of Epidemiology and Community Health and will provide the skills needed to successfully examine associations of maternal stress with characteristics of maternal milk and preterm infant gut composition in the R00 phase. Targeted and untargeted metabolic approaches and microbial analyses will be used to elucidate the relationships between human milk and preterm gut composition with maternal stress and preterm neurodevelopmental (Aim 3). The proposed research lays the groundwork for future clinical interventions designed to mitigate the effects of maternal postnatal stress through psychosocial support and/or nutritional supplementation and will also provide foundational data for the successful launch of an independent research career focused on promoting nutritional practices which yield optimal ne...