Opioid use disorders are a public health concern of epidemic proportion. Our project will contribute significantly to this COBRE Center on Opioids and Overdose, as misuse of opioids during pregnancy effects infants, our most vulnerable population. The focus of this project is on Neonatal Abstinence Syndrome (NAS), the withdrawal that infants suffer after being born to a mother who is dependent on opioids. NAS has increased fivefold since 2000, now affecting 60-80% of infants exposed to opioids in utero. The cost to treat NAS in 2012 was $1.5 billion with the majority of infants enrolled in state sponsored insurance programs. NAS is typically treated by the reintroduction of opioids (morphine or methadone and more recently, buprenorphine) followed by gradual weaning and increasingly with non-pharmacological interventions as well (e.g. rooming-in). Unfortunately, treatments are not evidence-based and there are no standardized protocols resulting in a wide variability in the management of these infants and the potential for mismanagement. The overall objective of this proposal is to develop the evidence based tools needed to define best practice and develop a standardized approach to improve the treatment and management of infants with NAS. Our central hypothesis is that establishment of a standardized perinatal to postnatal treatment program for maternal opioid dependency and the management of NAS will shorten length of stay and length of treatment, reduce health care costs, and prevent or mitigate potential adverse long term neurodevelopmental outcomes. In this project we propose to 1) develop a multi- disciplinary, buprenorphine-based prenatal care model for pregnant women being treated for opioid use disorders, 2) conduct a single center randomized control trial of buprenorphine vs. morphine for NAS, and 3) develop a preliminary Risk Stratification Safety Assessment tool (RSSA), using Classification and Regression Tree (CART) statistical decision making analysis to help determine which families are most at risk of medication noncompliance. By tailoring treatment prenatally and removing barriers to novel interventions and working synergistically with the Cores we will transform our current approach the treatment and management of NAS.