Project Summary Thomas Jefferson University Hospital (TJUH) is the main clinical campus of Thomas Jefferson University (TJU) and will serve as clinical site for the “HEAL Initiative: Neonatal Opioid Withdrawal Syndrome Pharmacological Treatments Comparative Effectiveness Trial - Clinical Sites” RFA- HD-21=031. The site will be led by the co-PI structure of Walter Kraft, MD (TJU) and Susan Adeniyi-Jones, MD (TJU and Nemours at Jefferson). TJU has a 40-year history of leadership in optimizing approaches to the care opioid use disorder in pregnancy at the Maternal Addiction Treatment, Education, and Research (MATER) program, which carries a maternal census of >200 women. The current investigative team has been leaders in conducting clinical trials examining the optimal pharmacological treatments for neonatal opioid withdrawal syndrome (NOWS). This work has included neonatal first use and pharmacometric driven dose optimization of buprenorphine. TJU was the national top enroller in the recently completed AIM2NAS study examining ondansetron as pharmacologic adjunct to reduce NOWS symptoms. These clinical trials, along with work in genetic sample collection, have enrolled over 450 infants in NOWS related research. TJUH engages in maximal non-pharmacologic care and has a well-established quality assessment and improvement program around NOWS care. There is a robust continuum of care that supports women with opioid use disorders before, during, and after delivery. This supportive culture has resulted in high rate of agreeing to participate in clinical trials (~70% of mothers approached) allows for longitudinal follow up of infants. Neurodevelopmental assessment is available for infants across the tri-state region catchment area of Philadelphia. The investigative team is experienced in the conduct and design of multi-center clinical trials and of data safety monitoring board functioning. The investigators have has been involved in national and international consortia dedicated to optimizing care in NOWS.