Prenatal Opioid Use Disorder Treatment—the Importance of Shared Decision-Making

Abstract

In this issue of JAMA Internal Medicine, Suarez et al 1 studied a population-based cohort of publicly insured pregnant individuals receiving methadone or buprenorphine for opioid use disorder (OUD) in the US. Their study adds considerably to the sparse literature on rates of congenital malformations among newborns with in utero exposure to buprenorphine and methadone. The authors found a 1% absolute risk reduction of congenital malformations from buprenorphine exposure compared with methadone. First-trimester exposure to methadone was associated with higher odds of cardiac malformations, oral clefts, and clubfoot than buprenorphine. In secondary analyses, they found that buprenorphine exposure was associated with higher odds of gastrointestinal-specific malformation, mostly pyloric stenosis.The authors use robust statistical methods to address residual confounding concerns, including propensity score matching to account for a greater percentage of the methadoneexposed cohort being a race or ethnicity other than White, living in urban areas, and having lower county-level socioeconomic status. 1 They conducted multiple sensitivity analyses, including using individuals who underwent secondtrimester initiation of medications for opioid use disorder (MOUD) as a negative control group under the conventional assumption that most teratogenicity can be attributed to firsttrimester exposures.Despite the cutting-edge statistical analyses, unmeasured environmental confounders may play a role in explaining the study findings. 1 However, additional research is needed to better understand potential mechanisms causing different effects of methadone and buprenorphine on organogenesis and congenital malformations. Prior work by Suarez's research group evaluating exposure to prescribed opioids using the same data source did not find a substantial increase in anomalies following first-trimester exposure to full μ-opioid receptor agonists. 2 Comparing the current study cohort with one of unexposed pregnancies would aid in the interpretation of the findings specific to methadone (a full μ-opioid receptor agonist) and buprenorphine (a partial μ-opioid receptor agonist). Similarly, the authors' new finding of an association between buprenorphine and pyloric stenosis is important. 1 However, it requires further investigation because pyloric stenosis is less clearly linked to first-trimester exposures than cardiac and neural tube anomalies.For clinicians treating patients who are newly pregnant or contemplating pregnancy, it is essential to place the study's findings in the context of the current phase of the opioid overdose epidemic. First, the pregnant individuals included in this study comprise a relatively stable group of patients with OUD-Invited Commentary and Editor's Note