Extended-Release vs Sublingual Buprenorphine in Pregnancy and Postpartum

Key Takeaways

• Extended-release buprenorphine was associated with higher illicit opioid abstinence during pregnancy.
• Abstinence declined postpartum and appeared similar in the two treatment groups.
• Serious adverse events were less frequent with extended-release, medication-related adverse events during pregnancy were more common, and infant NOWS treatment outcomes were similar.

This 2-group, open-label, noninferiority randomized clinical trial was conducted from July 2, 2020, to October 30, 2024, at 13 outpatient cross-disciplinary peripartum OUD treatment sites. It randomized 140 adults with opioid use disorder and singleton pregnancies at 6 to 30 weeks' gestation to extended-release or sublingual buprenorphine. Extended-release buprenorphine was given weekly during pregnancy, and a monthly postpartum formulation was optional for participants who were not breastfeeding. Mean age was 31.2 years, most participants were White, and all but 2 were already prescribed sublingual buprenorphine.

The primary outcome was illicit opioid abstinence during pregnancy, and the key secondary outcome was illicit opioid abstinence postpartum. Abstinence was defined as the proportion of weekly urine samples that were negative for illicit opioids during pregnancy and postpartum. Study completion was 98% through pregnancy and 81% through 12 months postpartum. Postpartum abstinence was 60.2% with extended-release buprenorphine and 59.5% with sublingual buprenorphine, a mean difference of 0.65 percentage points. The 98% confidence interval ranged from -12.72 to 14.02 percentage points, P = .45, and postpartum abstinence was similar between groups.

Maternal safety findings differed by outcome across pregnancy and postpartum. Serious adverse events during pregnancy occurred in 8.7% of the extended-release group and 26.8% of the sublingual group, with P = .007. Postpartum serious adverse events occurred in 6.0% and 18.6% of the groups, respectively, with P = .04, and nonserious adverse event rates did not differ. Medication-related adverse events during pregnancy were more common with extended-release buprenorphine, 26.1% versus 7.0%, with P = .003. Serious adverse events were less frequent with extended-release, while medication-related adverse events during pregnancy were more common.

Infant outcomes were obtained from medical records and included opioid treatment for neonatal opioid withdrawal syndrome and the number of opioid treatment days. Opioid treatment for neonatal opioid withdrawal syndrome occurred in 30.2% of extended-release-exposed infants and 26.5% of sublingual-exposed infants, with a relative risk of 1.14. Mean opioid treatment lasted 10.9 versus 14.8 days, with a relative risk of 0.73, and neither comparison differed significantly. Head circumference at birth was 34.0 versus 33.4 cm, a mean difference of 0.63 cm with a 95% confidence interval from -0.00 to 1.26 and P = .049. Infant treatment needs for neonatal opioid withdrawal syndrome were similar between groups, while head circumference at birth was modestly larger with extended-release exposure.