Objectives	Endpoints
Primary
• To evaluate the efficacy of a rapid-wean intervention compared with a slow-wean intervention in reducing the number of days of opioid treatment from the first dose of weaning to cessation of opioid among infants receiving an opioid (defined as morphine or methadone) as the primary treatment for neonatal opioid withdrawal syndrome (NOWS)	• The number of days of opioid treatment from the first dose of weaning to cessation of opioid
Secondary
• To evaluate the efficacy of a rapid-wean intervention compared with a slow wean intervention in reducing the number of days of opioid treatment from the first dose of weaning to cessation of opioid among infants treated with morphine as the primary treatment for neonatal opioid withdrawal syndrome (NOWS)	• The number of days of morphine treatment from the first dose of weaning to cessation of morphine
• To evaluate the efficacy of a rapid-wean intervention compared with a slow wean intervention in reducing the number of days of opioid treatment from the first dose of weaning to cessation of opioid among infants treated with methadone as the primary treatment for neonatal opioid withdrawal syndrome (NOWS)	• The number of days of methadone treatment from the first dose of weaning to cessation of methadone
• To determine whether a rapid- or slow-wean intervention affects escalation or resumption of opioid medication during weaning among infants receiving an opioid (defined as morphine or methadone) as the primary treatment for neonatal opioid withdrawal syndrome (NOWS)	• Escalation or resumption of morphine or methadone medication during weaning
• To determine whether a rapid- or slow-wean intervention affects the total amounts of opioid given from the first dose of weaning to cessation of opioid among infants receiving an opioid (defined as morphine or methadone) as the primary treatment for neonatal opioid withdrawal syndrome (NOWS)	• The total amount of morphine or methadone given from the first dose of weaning to cessation of opioid
• To determine whether a rapid- or slow-wean intervention affects the administration of second- or third-line drugs to treat NOWS from the first dose of weaning to cessation of opioid among infants receiving an opioid (defined as morphine or methadone) as the primary treatment for neonatal opioid withdrawal syndrome (NOWS)	• Initiation or escalation of second- or third-line drugs administered to treat NOWS signs from the first dose of weaning to cessation of opioid
• To evaluate the safety and tolerability of a rapid-wean intervention compared with a slow-wean intervention among infants receiving an opioid (defined as morphine or methadone) as the primary treatment for neonatal opioid withdrawal syndrome (NOWS)	• Seizures (clinical or EEG), excessive stool output, respiratory disturbances, and feeding tolerance
• To determine whether a rapid- or slow-wean intervention affects neurobehavior among infants receiving an opioid (defined as morphine or methadone) as the primary treatment for neonatal opioid withdrawal syndrome (NOWS)	• Atypical neurobehavioral profile prior to discharge on the NICU Network Neurobehavioral Scale (NNNS) after completion of study drug and prior to hospital discharge
• To determine whether a rapid- or slow-wean intervention affects the total length of hospital stay among infants receiving an opioid (defined as morphine or methadone) as the primary treatment for neonatal opioid withdrawal syndrome (NOWS)	• The total number of days spent in the hospital
• To determine whether a rapid- or slow-wean intervention among infants receiving an opioid (defined as morphine or methadone) as the primary treatment for neonatal opioid withdrawal syndrome (NOWS) affects maternal well-being and maternal infant attachment at 4 weeks (± 7 days) after discharge	• Parent-Reported Outcome Measure Information System (PROMIS) Measures at 1 month after discharge and at 24 months of age • Maternal Post Attachment Questionnaire (MPAQ) at one month after discharge
• To determine whether a rapid- or slow-wean intervention among infants receiving an opioid (defined as morphine or methadone) as the primary treatment for neonatal opioid withdrawal syndrome (NOWS) affects growth over the first 24 months of age	• Weight (kg), length (cm), head circumference (cm), and weight for length percentile on the World Health Organization (WHO) growth curves. Anthropometric z-scores and Body mass index (BMI)-z at 24 months of age
• To determine whether a rapid- or slow-wean intervention among infants receiving an opioid (defined as morphine or methadone) as the primary treatment for neonatal opioid withdrawal syndrome (NOWS) affects infant wellness after discharge and until 24 months of age	• Acute/urgent care and/or ER visits (total number of occurrences) (CQ) • Readmissions (number of occurrences) (CQ) • Death (presence or absence)
• To determine whether a rapid- or slow-wean intervention among infants receiving an opioid (defined as morphine or methadone) as the primary treatment for neonatal opioid withdrawal syndrome (NOWS) affects infant development.	• Bayley Scales of Infant and Toddler Development, Fourth Edition (Bayley 4): Cognitive, Language, Motor, at 24 months of age