Neurodevelopmental Outcomes of Neonates Randomized to Morphine or Methadone for Treatment of Neonatal Abstinence Syndrome

Abstract

To evaluate the effects of pharmacologic treatment of neonatal abstinence syndrome on neurodevelopmental outcome from a randomized, controlled trial. Eight sites enrolled 116 full-term newborn infants with neonatal abstinence syndrome born to mothers maintained on methadone or buprenorphine into a randomized trial of morphine vs methadone. Ninety-nine infants (85%) were evaluated at hospital discharge using the NICU Network Neurobehavioral Scale. At 18months, 83 of 99 infants (83.8%) were evaluated with the Bayley Scales of Infant and Toddler Development-Third Edition and 77 of 99 (77.7%) with the Child Behavior Checklist (CBCL). Primary analyses showed no significant differences between treatment groups on the NICU Network Neurobehavioral Scale, Bayley Scales of Infant and Toddler Development-Third Edition, or CBCL. However in post hoc analyses, we found differences by atypical NICU Network Neurobehavioral Scale profile on the CBCL. Infants receiving adjunctive phenobarbital had lower Bayley Scales of Infant and Toddler Development-Third Edition scores and more behavior problems on the CBCL. In adjusted analyses, internalizing and total behavior problems were associated with use of phenobarbital (P=.03; P=.04), maternal psychological distress (measured by the Brief Symptom Inventory) (both P<.01), and infant medical problems (both P=.02). Externalizing problems were associated with maternal psychological distress (P<.01) and continued maternal substance use (P<.01). Infants treated with either morphine or methadone had similar short-term and longer term neurobehavioral outcomes. Neurodevelopmental outcome may be related to the need for phenobarbital, overall health of the infant, and postnatal caregiving environment. ClinicalTrials.gov: NCT01958476.