First Trimester Use of Buprenorphine or Methadone and the Risk of Congenital Malformations

SPS commentary:

The researchers suggest from their findings that when determining optimal treatment for pregnant people with opioid use disorder, considerations should include relative risk reduction for malformations overall with buprenorphine vs methadone, as well as treatment access, previous success on a particular treatment, and the likelihood of retention in treatment.

Two commentaries from US perspective accompany this study. The first points out pregnancy may represent a specific window of opportunity to engage individuals in medications for opioid use disorder (MOUD), which leads to better outcomes for the maternal-infant dyad, but fewer than 1 in 4 individuals with OUD receive treatment in any given month of pregnancy. It emphasizes the benefits of any MOUD, including methadone, far outweigh the risks of abruptly stopping opioids or not using MOUD during pregnancy. It adds that in the absence of other concerns, switching medications (methadone to buprenorphine) or—worse—discontinuing MOUD because of this study runs counter to the substantial evidence regarding the safety of these medications during pregnancy, and no treatment is without risk in pregnancy. It suggests that understanding and conveying the risks in a measured way is an important part of consultation, especially for OUD where not receiving MOUD confers substantially increased morbidity and mortality.

The second commentary notes that despite the cutting-edge statistical analyses, unmeasured environmental confounders may play a role in explaining the study findings, and additional research is needed to better understand potential mechanisms causing different effects of methadone and buprenorphine on organogenesis and congenital malformations. It highlights that previous research on 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. It adds that 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). It concludes that 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 in the US.