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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Bibliographic Details
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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Summary: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.
ISSN:2044-6055