To the Editor:

A recent article on the use of buprenorphine for treatment of opioid use disorder (OUD) thoughtfully reviews common questions that may arise from the primary care clinician's perspective.¹ In reviewing dosing regimens for buprenorphine, the author comments that buprenorphine monoproducts are primarily intended for use in pregnancy because the naloxone present in combination buprenorphine-naloxone products is not approved for use in pregnancy.

Although this was previously accepted practice, subsequent systematic reviews and meta-analyses demonstrate the safety and effectiveness of buprenorphine-naloxone in pregnancy.^2,3 No significant differences in gestational age at delivery, birth parameters, or prevalence of congenital anomalies were demonstrated in patients receiving combination therapy vs monoproducts.³ Recent comparative evidence even favors the use of buprenorphine-naloxone over buprenorphine alone, given its lower risk of neonatal opioid withdrawal syndrome, neonatal intensive care unit admission, and small for gestational age diagnosis.⁴ These data affirm that both transmucosal products are reasonable choices in pregnancy.

Patients who are stable on buprenorphine-naloxone at the time of pregnancy should be counseled that it is safe to remain on this treatment without disruption. Patients initiating medications for OUD during pregnancy who prefer buprenorphine-naloxone should be affirmed in this choice. One study in nonpregnant young adults found that receipt of a medication for OUD that is congruent with patient preference may be associated with reduced opioid use and increased treatment adherence.⁵ This evidence further supports the addiction medicine and harm reduction principle of meeting patients where they are at.

In Reply:

I thank the writers for sharing this promising data on the safety of buprenorphine-naloxone in pregnancy, and the possibility of reducing the risk of neonatal abstinence syndrome (NAS).

The meta-analyses each reviewed the same limited collection of small retrospective studies.^1,2 One included five studies for a total of 1,875 pregnancies, and the other included seven studies for 302 pregnancies. Combining data from small retrospective studies allows for very limited confidence in results. The subsequent observational study with 5,385 total pregnancies with or without buprenorphine-naloxone exposure reported an overall rate of all major malformations of 5.2%.³ Although none of the rates for specific organ malformations were significantly different, they had fairly wide CIs.

For NAS, the first meta-analysis reported a rate of 37.4% with combination products vs 55.8% with buprenorphine only.¹ The number needed to treat with buprenorphinenaloxone to prevent 1 case of NAS is 6, making it a reasonable low-risk treatment to consider for pregnant patients when discussing their priorities and preferences. Some patients may value maintaining their current treatment or reducing the risk of NAS, whereas others may prioritize minimizing prenatal exposure to any unnecessary medications. An informed consent discussion should include the limitations of the available data, and the clinician should qualify their recommendations accordingly.