PROJECT ABSTRACT Perinatal substance use in the U.S. has increased over the past two decades, with now over 8% of pregnant people endorsing recent use of a federally illicit substance (including cannabis, opioids, and cocaine). For newborns with prenatal substance exposure, multiple care practices during the birth hospitalization require special consideration: 1) approaches to newborn toxicology testing, 2) monitoring and management for newborn withdrawal symptoms, 3) counseling about human milk feedings, and 4) psychosocial support for families. Each of these aspects of care may shape the earliest parenting experiences of families, including their first interactions with the health system as parents. Given the issues of stigmatization and criminalization that surround perinatal substance use, the quality of care for substance-exposed newborns varies widely, with Black families and families living in poverty most likely to experience outcomes like child welfare services reporting and family separation. Further research is needed to identify hospital care practices that are readily implemented and that improve healthcare quality and equity for substance-exposed newborns. This will be an explanatory sequential mixed methods study conducted with the Better Outcomes through Research for Newborns (BORN) Network. Established by the Academic Pediatric Association (APA) in 2010, BORN is the first and only national practice-based research network that focuses on birth hospitalization care for healthy term and late preterm newborns. As a network of over 130 hospitals across 40 states and representing 10% of all U.S. births, BORN presents an ideal opportunity to study newborn care across diverse practice settings that span the legal and epidemiologic landscape of perinatal substance use. All study aims will be co-conducted with EMPOWER (Empowering Mothers, Providers, and Others to Weigh in as Experts in Research), a unique multi-state collaborative of patient stakeholders with lived experience of perinatal substance use and formal training in research methods. For Aim 1, we will develop, pilot-test, and disseminate a cross-sectional survey to all BORN Network hospitals (N=131) to delineate the range of care practices related to newborn toxicology testing, rooming-in, human milk feeding, and psychosocial supports for families, and we will identify common patterns of care. In Aim 2, we will retrospectively evaluate associations between hospital practices and patient- level outcomes among a purposive sample of 15 BORN hospitals (N=1,500 substance-exposed newborns). We will conduct multilevel regression, adjusting for clinical and contextual confounders, with a focus on differences by payor status and race. In Aim 3, we will assess the barriers and facilitators to implementing high quality and equitable care for substance-exposed newborns by conducting qualitative interviews and in-depth policy review at 6 hospitals. We will integrate the quantitative and quali...