The finding:
The prevalence of opioid use disorder (OUD) in pregnancy increased markedly over the past 2 decades, reflecting a similar rise in the general population. Several health organizations have consistently recommended the treatment of OUD in pregnancy with methadone or buprenorphine to reduce the illicit use of opioids. Buprenorphine has also been shown to be equivalent and/or superior to methadone for the treatment of OUD. However, limited data exists studying the safety and efficacy of buprenorphine formulated with naloxone in pregnancy, a formulation intended to deter diversion via intranasal or intravenous use. This study compared 3,369 pregnant individuals exposed to buprenorphine plus naloxone during the first trimester to 5,326 exposed to buprenorphine alone or who switched from the combination to buprenorphine alone by the end of the first trimester. Compared with pregnant women treated with buprenorphine alone, patients who were prescribed buprenorphine/naloxone had a lower risk of having infants born with neonatal abstinence syndrome (37.4% versus 55.8%), neonatal intensive care unit (NICU) admissions (30.6% versus 34.9%), and small-for-gestational-age births (10.0% versus 12.4%) compared to buprenorphine alone. However, no significant differences were observed for congenital malformations, preterm birth, respiratory symptoms, low birth weight, or maternal morbidity. These findings suggest that buprenorphine combined with naloxone is a safe and viable option for treating OUD during pregnancy, providing some flexibility for treatment decisions.

Strength and weaknesses:
Strengths of this study include the use of a large nationwide cohort of Medicaid-insured pregnant women, greatly enhancing the generalizability of the findings, especially to populations most affected by OUD, although other populations, such as those with private insurance or uninsured groups may need further study. This study also looked at a broad range of neonatal and maternal outcomes, including neonatal abstinence syndrome, preterm births, NICU admissions, and congenital malformations, providing a comprehensive evaluation of safety. Extensive sensitivity analyses were performed, including high-dimensional propensity scoring and adjusting for prenatal care, which strengthened the validity of the findings. However, as with all observational studies, this study is subject to certain limitations inherent in its design. While methods were used to adjust for confounders, unmeasured factors, like severity of OUD, may have influenced the results. Also, some potential confounders such as alcohol use and cigarette smoking may be underreported or missing in the claims data, which could introduce bias. The study also relied on prescription fills as a measure of exposure but cannot confirm whether patients actually took the medications as prescribed. And for some rare outcomes, like specific organ system malformations, the sample size was insufficient to draw definitive conclusions as reflected by wide confidence intervals. In summary, the study is robust due to its large sample and sophisticated analytical methods, yet inherent limitations do exist simply by its observational nature and due to some gaps in data collection.

Relevance:
The findings of this study are highly relevant to C-L psychiatrists, particularly those working in health care settings where an addiction consult service is not available and may be asked to assist with the treatment of pregnant women with an OUD. C-L psychiatrists can confidently recommend buprenorphine/naloxone formulations during pregnancy, knowing that it is associated with similar or better neonatal and maternal outcomes compared to buprenorphine alone. This provides flexibility in treatment options, especially in cases where there is concern about misuse or diversion of buprenorphine. Thus, C-L psychiatrists can play a central role in managing OUD in pregnancy by guiding medication choices while considering patient preferences and risk factors.