Comparative effectiveness of methadone versus buprenorphine/naloxone during pregnancy on perinatal and neonatal health outcomes: protocol for a population-based target trial in British Columbia, Canada

Introduction Opioid use disorder (OUD) during pregnancy is associated with increased rates of adverse perinatal, foetal and neonatal health events. Opioid agonist treatment (OAT) can substantially reduce the risk of these potential harms. In British Columbia (BC), methadone and buprenorphine/naloxon...

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Main Authors: Lianping Ti, Bohdan Nosyk, Jeong Eun Min, B Carolina Guerra-Alejos, Megan Kurz, Lindsay A Wilson
Format: Article
Language:English
Published: BMJ Publishing Group 2025-08-01
Series:BMJ Open
Online Access:https://bmjopen.bmj.com/content/15/8/e095461.full
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author Lianping Ti
Bohdan Nosyk
Jeong Eun Min
B Carolina Guerra-Alejos
Megan Kurz
Lindsay A Wilson
author_facet Lianping Ti
Bohdan Nosyk
Jeong Eun Min
B Carolina Guerra-Alejos
Megan Kurz
Lindsay A Wilson
author_sort Lianping Ti
collection DOAJ
description Introduction Opioid use disorder (OUD) during pregnancy is associated with increased rates of adverse perinatal, foetal and neonatal health events. Opioid agonist treatment (OAT) can substantially reduce the risk of these potential harms. In British Columbia (BC), methadone and buprenorphine/naloxone are first-line treatment options for pregnant people with OUD. However, the comparative effectiveness of these regimens during pregnancy remains poorly understood, particularly in terms of how dosage may impact clinical outcomes. This protocol outlines a proposed population-based retrospective study to evaluate the comparative effectiveness of methadone compared with buprenorphine/naloxone during pregnancy on perinatal and neonatal health outcomes.Methods and analysis We propose to conduct a retrospective observational study using population-based data from individuals who received methadone or buprenorphine/naloxone during pregnancy between 1 April 2010 and 31 March 2022. Data will be collected from 10 linked population-level administrative databases. We will emulate target trials using intention-to-treat and per-protocol approaches. We will use a pooled logistic regression approach to assess the impact of methadone versus buprenorphine/naloxone on time to OAT episode discontinuation and a dose-response marginal structural model to evaluate neonatal health at delivery. An exploratory observational analysis will also be conducted to describe the impact of methadone vs buprenorphine exposure during the first trimester of pregnancy on congenital malformations and anomalies.Ethics and dissemination This study has been determined to meet the criteria for exemption per Article 2.5 of the 2018 Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans. Study databases have been made available by the BC Ministries of Health and Mental Health and Addiction as part of the provincial opioid overdose public health emergency response. Results will be disseminated to policymakers, clinical partners, community programmes and people with lived and living experience of substance use and published in peer-reviewed journals.
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spelling doaj-art-6cf2a27ea7da4c2280b2c7f0620f93122025-08-20T03:40:14ZengBMJ Publishing GroupBMJ Open2044-60552025-08-0115810.1136/bmjopen-2024-095461Comparative effectiveness of methadone versus buprenorphine/naloxone during pregnancy on perinatal and neonatal health outcomes: protocol for a population-based target trial in British Columbia, CanadaLianping Ti0Bohdan Nosyk1Jeong Eun Min2B Carolina Guerra-Alejos3Megan Kurz4Lindsay A Wilson5British Columbia Centre on Substance Use, Vancouver, British Columbia, CanadaCentre for Advancing Health Outcomes, Vancouver, British Columbia, CanadaCentre for Advancing Health Outcomes, Vancouver, British Columbia, CanadaCentre for Advancing Health Outcomes, Vancouver, British Columbia, CanadaCentre for Advancing Health Outcomes, Vancouver, British Columbia, CanadaSchool of Population and Public Health, University of British Columbia, Vancouver, British Columbia, CanadaIntroduction Opioid use disorder (OUD) during pregnancy is associated with increased rates of adverse perinatal, foetal and neonatal health events. Opioid agonist treatment (OAT) can substantially reduce the risk of these potential harms. In British Columbia (BC), methadone and buprenorphine/naloxone are first-line treatment options for pregnant people with OUD. However, the comparative effectiveness of these regimens during pregnancy remains poorly understood, particularly in terms of how dosage may impact clinical outcomes. This protocol outlines a proposed population-based retrospective study to evaluate the comparative effectiveness of methadone compared with buprenorphine/naloxone during pregnancy on perinatal and neonatal health outcomes.Methods and analysis We propose to conduct a retrospective observational study using population-based data from individuals who received methadone or buprenorphine/naloxone during pregnancy between 1 April 2010 and 31 March 2022. Data will be collected from 10 linked population-level administrative databases. We will emulate target trials using intention-to-treat and per-protocol approaches. We will use a pooled logistic regression approach to assess the impact of methadone versus buprenorphine/naloxone on time to OAT episode discontinuation and a dose-response marginal structural model to evaluate neonatal health at delivery. An exploratory observational analysis will also be conducted to describe the impact of methadone vs buprenorphine exposure during the first trimester of pregnancy on congenital malformations and anomalies.Ethics and dissemination This study has been determined to meet the criteria for exemption per Article 2.5 of the 2018 Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans. Study databases have been made available by the BC Ministries of Health and Mental Health and Addiction as part of the provincial opioid overdose public health emergency response. Results will be disseminated to policymakers, clinical partners, community programmes and people with lived and living experience of substance use and published in peer-reviewed journals.https://bmjopen.bmj.com/content/15/8/e095461.full
spellingShingle Lianping Ti
Bohdan Nosyk
Jeong Eun Min
B Carolina Guerra-Alejos
Megan Kurz
Lindsay A Wilson
Comparative effectiveness of methadone versus buprenorphine/naloxone during pregnancy on perinatal and neonatal health outcomes: protocol for a population-based target trial in British Columbia, Canada
BMJ Open
title Comparative effectiveness of methadone versus buprenorphine/naloxone during pregnancy on perinatal and neonatal health outcomes: protocol for a population-based target trial in British Columbia, Canada
title_full Comparative effectiveness of methadone versus buprenorphine/naloxone during pregnancy on perinatal and neonatal health outcomes: protocol for a population-based target trial in British Columbia, Canada
title_fullStr Comparative effectiveness of methadone versus buprenorphine/naloxone during pregnancy on perinatal and neonatal health outcomes: protocol for a population-based target trial in British Columbia, Canada
title_full_unstemmed Comparative effectiveness of methadone versus buprenorphine/naloxone during pregnancy on perinatal and neonatal health outcomes: protocol for a population-based target trial in British Columbia, Canada
title_short Comparative effectiveness of methadone versus buprenorphine/naloxone during pregnancy on perinatal and neonatal health outcomes: protocol for a population-based target trial in British Columbia, Canada
title_sort comparative effectiveness of methadone versus buprenorphine naloxone during pregnancy on perinatal and neonatal health outcomes protocol for a population based target trial in british columbia canada
url https://bmjopen.bmj.com/content/15/8/e095461.full
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