Morphine vs Methadone Treatment for Infants with Neonatal Abstinence Syndrome

Objective: To estimate the relationship of initial pharmacotherapy with methadone or morphine and length of stay (LOS) in infants with neonatal abstinence syndrome (NAS) admitted to the neonatal intensive care unit (NICU). Study design: From the Pediatrix Clinical Data Warehouse database, we identified all infants born at ≥36 weeks of gestation between 2011 and 2015 who were diagnosed with NAS (International Classification of Diseases, Ninth Revision code 779.5) and treated with methadone or morphine in the first 7 days of life. We used multivariable Cox proportional hazards regression analysis to quantify the association between initial treatment and LOS after adjusting for maternal age, maternal race/ethnicity, maternal drug use, maternal smoking, gestational age, small for gestational age status, inborn status, and discharge year. Results: We identified a total of 7667 eligible infants, including 1187 treated with methadone (15%) and 6480 treated with morphine (85%). Birth weight, gestational age, and sex were similar in the 2 groups. Methadone treatment was associated with a 22% shorter median LOS (18 days [IQR, 11-30 days] vs 23 days [IQR, 16-33]; P <.001) and a 19% shorter median NICU stay (17 days [IQR, 10-29 days] vs 21 days [IQR, 14-36 days]; P <.001). After adjustment, methadone was associated with a shorter LOS (hazard ratio for discharge, 1.24; 95% CI, 1.11-1.37; P <.001) Conclusion: Among infants born at ≥36 weeks of gestation with NAS, initial methadone treatment was associated with a shorter LOS compared with morphine treatment. Future prospective comparative effectiveness trials to treat infants with NAS are needed to verify this observation.