Introduction: This study aiming to provide vital insights into the potential impacts of these treatment modalities (morphine or methadone) on the neurodevelopmental trajectories of Neonatal Abstinence Syndrome (NAS) -affected infants. By investigating the potential disparities in neurodevelopmental outcomes associated with morphine and methadone, we aspire to inform evidence-based treatment decisions and refine the standard of care for NAS.

Material and Methods: Eight participating locations included 116 full-term newborns diagnosed with NAS, born to mothers under methadone or buprenorphine maintenance, who were enrolled in a randomized trial comparing morphine to methadone. Upon hospital discharge, 99 of these infants (representing 85% of the cohort) underwent assessment using the NICU Network Neurobehavioral Scale (NNNS). At the 18-month mark, 83 out of the 99 infants (approximately 83.8%) underwent evaluation employing the Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III), while the Child Behavior Checklist (CBCL) was administered to 77 of the 99 infants (around 77.7%).

Results: Our adjusted analyses further revealed that internalizing and total behavior problems were linked to the utilization of phenobarbital (p=0.03 and p=0.04, respectively), elevated levels of maternal psychological distress (as measured by the Brief Symptom Inventory) (both p<0.01), and the presence of infant medical issues (both p=0.02). Additionally, externalizing problems were associated with maternal psychological distress (p<0.01) and continued maternal substance use (p<0.01).

Conclusion: Neonates administered either morphine or methadone exhibited comparable neurobehavioral outcomes in both the short and long term. The neurodevelopmental progress of these infants may be associated with factors such as the requirement for phenobarbital, the general health of the infant, and the quality of postnatal caregiving.