Neonatal neurobehavior effects following buprenorphine versus methadone exposure

Addiction. 2012 Nov;107 Suppl 1(0 1):63-73. doi: 10.1111/j.1360-0443.2012.04040.x.

Abstract

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, 14-15 and 28-30.

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.

Trial registration: ClinicalTrials.gov NCT00271219.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Analgesics, Opioid / adverse effects*
  • Buprenorphine / adverse effects*
  • Female
  • Humans
  • Infant Behavior / drug effects*
  • Infant, Newborn
  • Linear Models
  • Male
  • Methadone / adverse effects*
  • Morphine / administration & dosage
  • Morphine / therapeutic use
  • Neonatal Abstinence Syndrome / drug therapy
  • Neonatal Abstinence Syndrome / physiopathology*
  • Opiate Substitution Treatment
  • Opioid-Related Disorders / drug therapy*
  • Pregnancy
  • Pregnancy Complications / drug therapy
  • Prenatal Exposure Delayed Effects
  • Severity of Illness Index
  • Young Adult

Substances

  • Analgesics, Opioid
  • Buprenorphine
  • Morphine
  • Methadone

Associated data

  • ClinicalTrials.gov/NCT00271219