Neonatal Opioid Withdrawal Syndrome: A Comparison of As-Needed Pharmacotherapy

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Background and objective: Methadone and morphine are commonly administered medications for neonatal opioid withdrawal syndrome (NOWS). Infants are increasingly treated with as-needed or "pro re nata" (PRN) medication. The optimal pharmacologic agent for PRN treatment of NOWS has not been examined. This study's objective is to compare NOWS hospital outcomes between infants treated with PRN methadone versus morphine.

Methods: We performed a retrospective cohort study of infants pharmacologically treated for NOWS across 4 Massachusetts hospitals between January 2018 and February 2021. Infants born ≥36 weeks gestation with prenatal opioid exposure treated with PRN methadone or morphine were included. Mixed effects logistic and linear regression models were employed to evaluate differences in transition rates to scheduled dosing, length of stay, and number of PRN doses administered depending on PRN treatment agent.

Results: There were 86 infants in the methadone group and 52 in the morphine group. There were no significant differences in NOWS hospital outcomes between groups in adjusted models: transition to scheduled dosing (methadone 31.6% vs morphine 28.6%, adjusted odds ratio 1.21, 95% confidence interval [CI] 0.87-1.19), mean length of stay (methadone 15.5 vs morphine 14.3 days, adjusted risk ratio 1.06, 95% CI 0.80-1.41), and the mean number of PRN doses (methadone 2.3 vs morphine 3.4, adjusted risk ratio 0.65, 95% CI 0.41-1.02). There was an association with nonpharmacologic care practices and improved NOWS hospital outcomes.

Conclusions: There were no significant differences in NOWS hospitalization outcomes based on pharmacologic agent type; nonpharmacologic care practices were most strongly associated with improved NOWS hospitalization outcomes.