Buprenorphine compared with methadone to treat pregnant women with opioid use disorder: a systematic review and meta‐analysis of safety in the mother, fetus and child

Abstract

AimsTo assess the safety of buprenorphine compared with methadone to treat pregnant women with opioid use disorder.MethodsWe searched PubMed, Embase and the Cochrane Library from inception to February 2015 for randomized controlled trials (RCT) and observational cohort studies (OBS) that compared buprenorphine with methadone for treating opioid‐dependent pregnant women. Two reviewers assessed independently the titles and abstracts of all search results and full texts of potentially eligible studies reporting original data for maternal/fetal/infant death, preterm birth, fetal growth outcomes, fetal/congenital anomalies, fetal/child neurodevelopment and/or maternal adverse events. We ascertained each study's risk of bias using validated instruments and assessed the strength of evidence for each outcome using established methods. We computed effect sizes using random‐effects models for each outcome with two or more studies.ResultsThree RCTs (n = 223) and 15 cohort OBSs (n = 1923) met inclusion criteria. In meta‐analyses using unadjusted data and methadone as comparator, buprenorphine was associated with lower risk of preterm birth [RCT risk ratio (RR) = 0.40, 95% confidence interval (CI) = 0.18, 0.91; OBS RR = 0.67, 95% CI = 0.50, 0.90], greater birth weight [RCT weighted mean difference (WMD) = 277 g, 95% CI = 104, 450; OBS WMD = 265 g, 95% CI = 196, 335] and larger head circumference [RCT WMD = 0.90 cm, 95% CI = 0.14, 1.66; OBS WMD = 0.68 cm, 95% CI = 0.41, 0.94]. No treatment differences were observed for spontaneous fetal death, fetal/congenital anomalies and other fetal growth measures, although the power to detect such differences may be inadequate due to small sample sizes.ConclusionsModerately strong evidence indicates lower risk of preterm birth, greater birth weight and larger head circumference with buprenorphine treatment of maternal opioid use disorder during pregnancy compared with methadone treatment, and no greater harms.

Management of opioid use disorders: a national clinical practice guideline

“…75,76 Abundant supporting evidence has rendered methadone the most frequently prescribed opioid agonist during pregnancy; however, more recent research suggests that buprenorphine (monoproduct) may be similarly safe and effective for the treatment of opioid use disorder in pregnant women. 75,[77][78][79] We suggest that care providers seek specialist consultation as needed to determine, on a case-by-case basis, the appropriate agent for opioid agonist treatment of a pregnant patient. Withdrawal management is not suggested during pregnancy, primarily because of the high rates of relapse and the adverse outcomes associated with rapid withdrawal and subsequent relapse, such as maternal and fetal distress, fetal death, fetal hypoxia, preterm labour and long-term developmental issues.…”

Opioid Use in Pregnancy, Neonatal Abstinence Syndrome, and Childhood Outcomes

“…(75, 76) Since these studies are limited by small sample size and confounding factors(17, 77) additional well-designed studies are needed. In a meta-analysis of three randomized controlled trials (n = 223) and 15 observational studies (n = 1923) that compared buprenorphine and methadone treatment in pregnancy no difference in the risk of congenital anomalies was identified.…”

Buprenorphine with, or without, Naloxone for Pregnant Women?–Review of Current Evidence and Practice in Massachusetts

“…Importantly, buprenorphine's ceiling effect decreases the risk of overdose [8,12,13]. Buprenorphine has been associated with improved outcomes in fetal growth, while causing less neonatal abstinence syndrome when compared to methadone [20][21][22][23]. In 2012, a randomized clinical trial, observed better surrogate measures of fetal well-being via non-stress test and biophysical profile post-dosing of buprenorphine versus methadone [24].…”