Attending Physician Cooper University Healthcare, New Jersey
Background & Introduction: The use of extended-release buprenorphine (XR-BUP) as a treatment for opioid use disorder (OUD) during pregnancy is an emerging area of interest, but, like many medications and their use in pregnancy, remains under studied.
Preclinical studies of the primary solvent in both currently marketed monthly XR-BUP formulations, N-methyl-pyrrolidone (NMP), demonstrate developmental toxicity at high doses, but suggest a threshold effect at lower doses (approx. 125mg/kg/day orally) with “no discernible differences from control animals”1,2,3. These ‘threshold doses’ are higher than the cumulative exposure of NMP assuming 10 injections over the course of a pregnancy.
Accordingly, XR-BUP is not contraindicated in pregnancy- with FDA labeling recommending using the medication when the potential benefits outweigh ‘potential risk to fetus4. Smaller human studies have demonstrated safety and efficacy of XR- BUP in pregnancy.5,6
Recognizing the limited literature about XR-BUP in pregnancy, this study utilizes data from pregnant individuals seeking care at a low barrier urban addiction medicine practice with one of the largest XR-BUP programs on the East Coast. We sought to better understand characteristics of individuals who started or maintained care on XR-BUP during their pregnancy.
Methods: We conducted a retrospective data pull of patients engaged in care at a low-barrier office-based opioid treatment center who were pregnant and concurrently receiving XR-BUP injections between 01/01/2019-06/01/2025. Of 11 eligible patients, manual chart abstraction was conducted to collect patient demographics, treatment history, pregnancy course, maternal treatment status at 1, 3, and 12 months postpartum, and infant outcomes. One patient was excluded due to incomplete records, and data were available for only nine of the infants. Descriptive statistics were used to summarize maternal and infant characteristics as well as treatment data.
Results: Among the 10 patients who received XR-BUP in pregnancy, 7 identified as White/Caucasian and 3 identified as Black, Latinx or ‘Other”. Patient ages ranged from 27 to 41. Most patients (9/10) were publicly insured, consistent with the general clinic population, and 90% were stably housed. The majority were multiparous, with most being gravida 3 or higher. 4 patients initiated XR-BUP during pregnancy, whereas 6 were continuing XR-BUP that had been started prior to pregnancy diagnosis.
Treatment exposure varied: five patients received 1-2 XR-BUP doses during pregnancy, two patients received 3-4 doses, and three patients received 9+ doses. All three patients who were on sequential XR-BUP injections at the time of delivery were concurrently prescribed 24-32mg of supplemental SL-BUP. All patients delivered at term. One infant had a congenital malformation, comparable to the population-wide baseline rate(~ 3%). 4 of the 9 infants were diagnosed with NAS/NOWS and received pharmacotherapy.
At 9 months postpartum, 9 of 10 patients remained on some form of MOUD, including 4 who continued XR-BUP. 60% were in remission at 12 months postpartum, though no clear correlation was observed between XR-BUP administration and abstinence from non-prescribed opioids. No patients were lost to follow up at 12 months postpartum.
Conclusion & Discussion: This retrospective analysis is limited by its small sample size, lack of randomization, and incomplete infant outcome data due to separate institutional blinding of NOWS treatment. Provider-level factors also likely influenced prescribing decisions, given that XR-BUP remains off-label in pregnancy. These limitations restrict the ability to draw definitive conclusions about XR-BUP’s effectiveness during pregnancy.
Nonetheless, our findings suggest potential disparities in candidacy for XR-BUP, with younger ( < 27), nonwhite, nulliparous, unhoused, or privately insured patients as a potential future target populations for more intensive education and outreach about XR-BUP in pregnancy. This study adds to the emerging evidence supporting XR-BUP’s safety in pregnancy, but larger controlled studies are necessary to confirm safety, identify which populations that may benefit most, and establish its comparative effectiveness against sublingual buprenorphine.
References: Galati, B. M., Wenzinger, M., Rogers, C. E., Cooke, E., & Kelly, J. C. (2023). Buprenorphine extended-release treatment for opioid use disorder in the postpartum period. Obstetrics & Gynecology, 142(5), 1148-1152.
Solomon, G. M., Morse, E. P., Garbo, M. J., & Milton, D. K. (1996). Stillbirth after occupational exposure to N-methyl-2-pyrrolidone: a case report and review of the literature. Journal of Occupational and Environmental Medicine, 38(7), 705-713.
Saillenfait, A. M., Gallissot, F., Langonne, I., & Sabate, J. P. (2002). Developmental toxicity of N-methyl-2-pyrrolidone administered orally to rats. Food and Chemical Toxicology, 40(11), 1705-1712.
Hubbell, A., Aghenta, E., Jones, C., & Specker, S. (2024). Extended-release buprenorphine in pregnancy. The American journal on addictions, 33(3), 354-356.
Disclosure(s):
Winney Zhao, MPH: No financial relationships to disclose
Mollie B. Nisen, MD, FASAM: No financial relationships to disclose
Learning Objectives:
Upon completion, participants will be able to summarize current knowledge and research gaps regarding long-acting buprenorphine treatment during pregnancy.
Upon completion, participants will be able to identify some of the maternal and infant outcomes associated with XR-BUP exposure during pregnancy and the postpartum period.
Upon completion, participants will be able to discuss how long-acting buprenorphine formulations may reduce barriers to care and advance health equity among pregnant patients with opioid use disorder.
