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
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.