Neonatal neurobehavior effects following buprenorphine versus methadone exposure

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 sub-study. Setting Medical Centers that provided comprehensive maternal care to opioid-dependent pregnant women in Baltimore, MD, Providence, RI, and Vienna, Austria. Participants 39 full-term infants. Measurements The 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), and 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 negatively correlated 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 positively related 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.

PlacentalHTR2Amethylation is associated with infant neurobehavioral outcomes

“…31 Prior studies analyzing components of the Barker hypothesis have focused on infants developing in more extreme environmental conditions, 27 or from mothers with high-risk pregnancies. 3,32 This study suggests that there is a level of epigenetic variability even among healthy infants and that this may result from more prevalent environmental conditions and stressors that are most likely experienced by the population at large.…”

“…1 In a short window of time during early prenatal development, neural networks are formed and behavioral pathways are programmed, and this programming is vulnerable to environmental influences. 2 Environmental factors, including maternal stress, mood, and lifestyle, have been linked to altered neurodevelopmental programming and later life behavioral and neurologic outcomes, 3,4 but the molecular mechanisms underlying these relationships remain unclear. 5 The fetal environment is modulated by the placenta, which produces growth factors, neuropeptides and components of monoamine transporter systems, and has been described as a "third brain" linking the mother and infant.…”

The Prescription Opioid and Heroin Crisis: A Public Health Approach to an Epidemic of Addiction

“…Both buprenorphine and methadone treatment are associated with reduced overdose risk and improved maternal and fetal outcomes in pregnancy (19,44,51,72). Despite strong evidence supporting the use of buprenorphine and methadone, fewer than 1 million Americans are receiving these treatments (87).…”

Developmental Consequences of Fetal Exposure to Drugs: What We Know and What We Still Must Learn

“…The American College of Obstetricians and Gynecologists has urged that buprenorphine be considered first-line treatment, but methadone is likely still the gold standard due to slightly higher adherence, more tightly controlled dosing, and insufficient evidence that buprenorphine is superior than methadone treatment (ACOG Committee, 2012). Observation of clinical cohorts has suggested that prenatal buprenorphine may produce fewer neurobehavioral problems (Coyle et al, 2012), higher birthweight, and larger head circumference compared with methadone (Welle-Strand et al, 2013).…”