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

Barbara K Zedler; Ashley L Mann; Mimi M Kim; Halle R Amick; Andrew R Joyce; E Lenn Murrelle; Hendrée E Jones

doi:10.1111/add.13462

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

Addiction. 2016 Dec;111(12):2115-2128. doi: 10.1111/add.13462. Epub 2016 Jun 30.

Authors

Barbara K Zedler¹, Ashley L Mann¹, Mimi M Kim², Halle R Amick¹, Andrew R Joyce¹, E Lenn Murrelle¹, Hendrée E Jones^{3

4}

Affiliations

¹ Venebio Group, LLC, Richmond, Virginia, USA.
² Center for Biobehavioral Health Disparities Research, Division of Community Health, Duke University, Durham, NC, USA.
³ UNC Horizons, Department of Obstetrics and Gynecology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁴ Departments of Psychiatry and Behavioral Sciences and Obstetrics and Gynecology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.

Abstract

Aims: To assess the safety of buprenorphine compared with methadone to treat pregnant women with opioid use disorder.

Methods: We 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.

Results: Three 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.

Conclusions: Moderately 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.

Keywords: Buprenorphine; dependence; fetus; harm; methadone; opioid use disorder; pregnancy.

Publication types

Comparative Study
Meta-Analysis
Review
Systematic Review

MeSH terms

Abnormalities, Drug-Induced / prevention & control
Analgesics, Opioid / therapeutic use*
Birth Weight / physiology
Buprenorphine / therapeutic use*
Female
Fetal Death / prevention & control
Fetal Development / drug effects
Humans
Infant, Newborn
Methadone / therapeutic use*
Opiate Substitution Treatment / methods
Opioid-Related Disorders / rehabilitation*
Patient Safety
Pregnancy
Pregnancy Complications / rehabilitation*
Pregnancy Outcome
Premature Birth / prevention & control
Prenatal Care / methods
Randomized Controlled Trials as Topic
Sudden Infant Death / prevention & control

Substances

Analgesics, Opioid
Buprenorphine
Methadone