Addiction Journal Club Review

Mono or Combo, That Is the Question: Comparative Safety of In Utero Exposure to Buprenorphine Combined with Naloxone vs. Buprenorphine Alone

By Dr. Ali ABY Muhammed

The question of whether to use buprenorphine alone or in combination with naloxone during pregnancy is critical in balancing maternal treatment needs with fetal safety. Buprenorphine is an established medication for opioid use disorder (OUD) in pregnancy, reducing illicit opioid use and improving maternal outcomes. Traditionally, the mono formulation has been preferred to avoid fetal exposure to naloxone.

This month, we are reviewing:Straub, L., Bateman, B. T., Hernández-Díaz, S., Zhu, Y., Suarez, E. A., Vine, S. M., Jones, H. E., Connery, H. S., Davis, J. M., Gray, K. J., Lester, B., Terplan, M., Zakoul, H., Mogun, H., & Huybrechts, K. F. (2024). Comparative safety of in utero exposure to buprenorphine combined with naloxone vs buprenorphine alone. JAMA, 332(10), 805–816. https://doi.org/10.1001/jama.2024.11501

The study compared neonatal and maternal outcomes in infants with in utero exposure to buprenorphine–naloxone versus buprenorphine alone. Findings suggest that the combination product does not significantly increase adverse outcomes such as low birth weight, preterm delivery, or severity of neonatal opioid withdrawal syndrome (NOWS). Maternal stability and treatment adherence appeared comparable across both groups.

These results support the evolving view that buprenorphine–naloxone may be a safe and effective option in pregnancy when clinically indicated, particularly when diversion risk is a concern. Still, further research with larger cohorts and long-term developmental follow-up remains essential.

Clinical takeaway: Treatment decisions should remain individualized, balancing maternal recovery stability, diversion risk, and the growing body of safety data. This study contributes meaningfully to the conversation, offering reassurance that the combination product may be a reasonable alternative to monotherapy for pregnant patients with OUD.