Extended-Release vs Sublingual Buprenorphine in Pregnancy Through 12 Months Post Partum: A Randomized Clinical Trial

Introduction

Opioid use disorder (OUD) during pregnancy poses significant risks to both mother and child, including preterm birth and neonatal opioid withdrawal syndrome (NOWS). While sublingual buprenorphine is a current standard of care, its daily dosing can lead to adherence challenges and fluctuating drug levels. This study explores whether a weekly extended-release formulation offers superior outcomes, addressing key gaps in maternal addiction treatment. Understanding these options is critical for improving prenatal care in OUD.

Study Design and Methodology

This open-label, randomized clinical trial enrolled 140 pregnant adults with OUD at 13 outpatient sites across the U.S. between July 2020 and October 2024. Participants, averaging 31.2 years in age and predominantly White (82.9%), were at 6–30 weeks’ gestation with singleton pregnancies. Most were already on sublingual buprenorphine. They were randomized to either continue sublingual treatment or switch to weekly extended-release injections during pregnancy, with monthly options postpartum if not breastfeeding. The study assessed non-inferiority with a 0.15 margin, then superiority, using urine tests to measure illicit opioid abstinence weekly. Infant outcomes included NOWS treatment need and duration.

Key Results

During pregnancy, extended-release buprenorphine demonstrated superior effectiveness: abstinence rates were 82.5% versus 72.6% for sublingual (mean difference 9.84 percentage points; P=0.009). Postpartum rates were comparable but lower overall (approximately 60% for both). Safety advantages were pronounced: extended-release users had fewer serious adverse events in pregnancy (8.7% vs 26.8%; P=0.007) and postpartum (6.0% vs 18.6%; P=0.04). However, non-serious medication-related events were higher in the extended-release group during pregnancy (26.1% vs 7.0%; P=0.003). Infant outcomes showed no significant differences in NOWS treatment needs or days, though extended-release-exposed neonates had slightly larger head circumferences (34.0 cm vs 33.4 cm; P=0.049), hinting at potential neurodevelopmental benefits.

Discussion and Clinical Relevance

The trial strongly supports extended-release buprenorphine for pregnancy OUD treatment, as it enhances abstinence and reduces serious risks. This formulation’s steady drug delivery may minimize withdrawal symptoms and improve adherence. Safety findings should be balanced against minor side effects like injection-site reactions. Crucially, infant outcomes remained safe, reassuring providers about fetal exposure. This evidence could shift guidelines, as extended-release options offer a pragmatic solution for high-risk pregnancies. Future research should explore long-term child development and real-world implementation in diverse populations.

Conclusion

This trial provides robust evidence for weekly extended-release buprenorphine as a preferred treatment for OUD in pregnancy, improving maternal outcomes without compromising infant safety. Its integration into prenatal care could reduce relapse and adverse events, ultimately supporting healthier pregnancies and families.

Trial Registration and Citation

ClinicalTrials.gov Identifier: NCT03918850. Citation: Winhusen TJ et al. JAMA Internal Medicine. 2026;186(5):533-543. PMID: 41837971. Full text available via URL: https://pubmed.ncbi.nlm.nih.gov/41837971/