Examining buprenorphine compared to methadone for likelihood of overdose during pregnancy, 2014–2021

Abstract Objective To examine the likelihood of experiencing an overdose among women receiving any buprenorphine (with or without naloxone) compared to women receiving methadone during pregnancy. Methods Data from the MATernaL and Infant clinical NetworK (MAT‐LINK), a longitudinal surveillance system of pregnant woman–child dyads using electronic health records (EHRs), were analyzed. Women from geographically diverse US clinical sites who had a diagnosis of opioid use disorder (OUD) during pregnancy, were prescribed medication for opioid use disorder (MOUD), and had a known birth outcome occurring between January 1, 2014 and August 31, 2021 were included. The Andersen–Gill Cox regression model for recurrent events with robust standard errors was used to model the effect of MOUD type by trimester on time to overdose or date of pregnancy outcome and calculate adjusted hazard ratios (aHRs). Results Among the 3682 pregnancies included in this analysis, 46 (1.2%) had at least one EHR‐documented overdose. None of the overdoses were fatal. In adjusted models, no differences in overdose were observed between pregnancies in which buprenorphine was prescribed or administered compared to pregnancies in which methadone was prescribed or administered (any drug overdose: aHR, 0.62; 95% CI, 0.31–1.23; opioid‐involved overdose: aHR, 0.49; 95% CI, 0.18–1.30). In a trimester‐specific sub‐analysis of pregnancies with at least two MOUD prescriptions or administrations, taking buprenorphine in the third trimester resulted in a decreased likelihood of any drug overdose (aHR, 0.43; 95% CI, 0.20–0.93) and opioid‐involved overdose (aHR, 0.32; 95% CI, 0.11–0.92) compared with methadone. Conclusion It is important that women with OUD are initiated on the medication that works best for them as early as possible during pregnancy and that reinforcement of the importance of MOUD occurs throughout pregnancy, paying special attention to disruptions in treatment during the third trimester that might increase risk for overdose.