Two Studies Investigate the Impact of Buprenorphine Dose and Duration Among Pregnant Patients With Opioid Use Disorder

In the US, opioid use disorder (OUD) during the perinatal period contributes to substantial maternal morbidity and mortality and adverse neonatal outcomes, including neonatal opioid withdrawal syndrome (NOWS). Medications for OUD, buprenorphine and methadone, are the standard of care for pregnant patients with OUD. However, real-world data on the impact of buprenorphine dose and consistency of administration throughout pregnancy are limited. Two recent observational studies examined associations between buprenorphine dose during pregnancy and neonatal and/or maternal outcomes.

In France, Marc et al conducted a retrospective electronic health record analysis of 75 non-preterm infants (³37 weeks gestation) admitted to two neonatal intensive care units (NICU) for treatment of NOWS (Lipsitz score of ≥4), born to mothers treated with buprenorphine during pregnancy, 2010–2020.

• The infants were grouped into three antenatal buprenorphine dose exposure categories: high-dose (³12mg), low-dose (2–11mg), and very low-dose (<2 mg).
• Duration of NOWS, hospital length of stay, and required total amount of morphine to treat NOWS were all significantly higher among infants whose mothers received high-dose buprenorphine, compared with those who received low or very low doses.

In the US, Jarlenski et al conducted a retrospective analysis of Pennsylvania Medicaid administrative data of 2925 pregnant patients with an OUD diagnosis, a live birth, and two or more buprenorphine prescriptions during pregnancy or postpartum, 2009–2019. Patients who received methadone were excluded.

• Group-based trajectory modeling identified eight patient longitudinal buprenorphine dose and duration trajectories.
• Compared with patients receiving higher and longer-duration buprenorphine doses initiated pre-pregnancy and continued (mean daily dose, 22.35 mg), those who initiated or discontinued buprenorphine during pregnancy were more likely to have discontinued buprenorphine 90-days postpartum and more likely to have experienced a non-fatal overdose.
• Receipt of high-dose buprenorphine and for longer duration during pregnancy was not associated with increased odds of neonatal abstinence syndrome or low infant birth weight, compared with receipt of moderate (mean daily dose, 14.76 mg) or low-dose (mean daily dose, 6.97 mg) buprenorphine initiated pre-pregnancy, or with shorter treatment duration.

Comments: Buprenorphine should be continued in patients with OUD who are pregnant and postpartum. The dose may need to be increased or adjusted (split) due to physiologic changes resulting from pregnancy using a patient-centered approach. In France, it is typical for lower doses of buprenorphine to be used, and fentanyl appears to minimally contribute to the nation’s drug supply and overdoses; fentanyl emerged in Pennsylvania in 2017. In Marc et al, NOWS was determined and monitored using the Lipsitz score, while in the US, standard of care is moving from the Finnegan Neonatal Abstinence Scoring Tool (FNAST) to the Eat, Sleep, Console (ESC) care approach. Use of ESC, a function-based approach, results in shorter hospital lengths of stay and lower pharmacologic interventions for neonates with NOWS.

Ximena A. Levander, MD

References:

Marc B, Marion D, François B, Lakshmipriya L. Is buprenorphine maternal dose associated with neonatal opioid withdrawal syndrome severity? Am J Addict. 2025;34(1):15–20.

Jarlenski M, LoCiganic WH, Chen Q, et al. Association between buprenorphine dose and outcomes among pregnant persons with opioid use disorder. Am J Obstet Gynecol. 2025;233(1):59.e1-59.e15.