Neonatal neurobehavior effects following buprenorphine versus methadone exposure

Aim To determine the effects of in utero exposure to methadone or buprenorphine on infant neurobehavior. Design Three sites from the Maternal Opioid Treatment: Human Experimental Research (MOTHER) study, a double-blind, double-dummy, randomized clinical trial participated in this substudy. Setting Medical Centers that provided comprehensive maternal care to opioid-dependent pregnant women in Baltimore, MD, Providence, RI and Vienna, Austria. Participants Thirty-nine full-term infants. Measurements The Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scale (NNNS) was administered to a subgroup of infants on postpartum days 3, 5, 7, 10, 1415 and 2830. Findings While neurobehavior improved for both medication conditions over time, infants exposed in utero to buprenorphine exhibited fewer stress-abstinence signs (P<0.001), were less excitable (P<0.001) and less over-aroused (P<0.01), exhibited less hypertonia (P<0.007), had better self-regulation (P<0.04) and required less handling (P<0.001) to maintain a quiet alert state relative to in utero methadone-exposed infants. Infants who were older when they began morphine treatment for withdrawal had higher self-regulation scores (P<0.01), and demonstrated the least amount of excitability (P<0.02) and hypertonia (P<0.02) on average. Quality of movement was correlated negatively with peak NAS score (P<0.01), number of days treated with morphine for NAS (P<0.01) and total amount of morphine received (P<0.03). Excitability scores were related positively to total morphine dose (P<0.03). Conclusion While neurobehavior improves during the first month of postnatal life for in utero agonist medication-exposed neonates, buprenorphine exposure results in superior neurobehavioral scores and less severe withdrawal than does methadone exposure.