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

Research output: Contribution to journalReview article

  • 33 Citations

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.

LanguageEnglish (US)
Pages2115-2128
Number of pages14
JournalAddiction
Volume111
Issue number12
DOIs
StatePublished - Dec 1 2016

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Buprenorphine
Methadone
Opioid Analgesics
Meta-Analysis
Pregnant Women
Fetus
Mothers
Confidence Intervals
Safety
Observational Studies
Premature Birth
Cohort Studies
Randomized Controlled Trials
Fetal Death
Fetal Development
Birth Weight
Odds Ratio
PubMed
Sample Size
Libraries

Keywords

  • Buprenorphine
  • dependence
  • fetus
  • harm
  • methadone
  • opioid use disorder
  • pregnancy

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Psychiatry and Mental health

Cite this

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

In: Addiction, Vol. 111, No. 12, 01.12.2016, p. 2115-2128.

Research output: Contribution to journalReview article

Zedler, Barbara K. ; Mann, Ashley L. ; Kim, Mimi M. ; Amick, Halle R. ; Joyce, Andrew R. ; Murrelle, E. Lenn ; Jones, Hendrée E./ 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. In: Addiction. 2016 ; Vol. 111, No. 12. pp. 2115-2128
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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.",
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AU - Amick,Halle R.

AU - Joyce,Andrew R.

AU - Murrelle,E. Lenn

AU - Jones,Hendrée E.

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N2 - 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.

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