PROJECT SUMMARY/ABSTRACT The medical and non-medical use of opioids and other psychoactive drugs in women of childbearing age is a significant public health concern in the United States. Prolonged in utero exposure of the developing fetus to maternal opioids often results in Neonatal Opioid Withdrawal Syndrome (NOWS) after delivery. Infants with NOWS may have mild signs of withdrawal that minimally impact their ability to function or they may have significant withdrawal that requires a prolonged course of pharmacologic therapy and a lengthy newborn hospital stay which stresses families, communities, and the healthcare system. Prolonged hospitalization may result in decreased maternal and infant bonding and attachment and have a negative impact on neurodevelopmental and behavioral outcomes of affected children. The prevalence of opioid use during pregnancy and the subsequent occurrence of NOWS after delivery is disproportionately higher in rural and underserved areas. Kentucky is a highly rural and underserved state and has an estimated rate of NOWS that is approximately three times the national average. Despite the significance of this problem, the clinical care for neonates with NOWS is complicated by a lack of nationally accepted standardized approaches which leads to significant site-to-site variation. Such variation is due in part to a lack of generalizable evidence to inform clinical practice. Previous research has been limited by both small sample sizes, due to difficulty with recruitment and retention, and inherent limitations in study designs. In order to identify the most effective treatment and thereby optimize the care of infants with NOWS, a direct comparison of pharmacologic treatment regimens in a generalizable population is urgently needed. Collaboration with local community partners and with other clinical sites will be undertaken within the proposed research consortium to design, implement, and conduct a multicenter randomized controlled clinical trial. The goal of the trial is to provide a direct comparison of pharmacologic treatment for infants with NOWS, account for confounding variables such as non-pharmacologic care and adjuvant medications and evaluate neurodevelopmental and behavioral outcomes in the first years of life. The anticipated results of this RCT will be highly generalizable to improve care for infants with NOWS in KY and throughout the nation.

PROJECT NARRATIVE The increased use and misuse of opioids during pregnancy and resulting Neonatal Opioid Withdrawal Syndrome (NOWS) are critical public health concerns in the United States. We will collaborate as a member of the proposed research group to design and conduct a multicenter clinical trial to directly compare the effectiveness of pharmacologic treatments for infants with NOWS. We anticipate that our studies will identify the optimal treatment for NOWS to improve the care and overall health and neurodevelopmental outcomes of infants with NOWS throughout the US.