Researchers found a small increased risk seen with methadone compared to buprenorphine but emphasize that both therapies are strongly recommended over untreated opioid use disorder during pregnancy
Buprenorphine or methadone can help prevent expecting mothers with opioid use disorder (OUD) from experiencing withdrawal symptoms, decrease opioid exposure and reduce the risk of overdose. The choice of treatment-buprenorphine or methadone-is influenced by factors such as treatment access, patient preference, established stability on a given treatment prior to pregnancy, and likelihood of continued retention in treatment. Comparative safety is another important consideration. A new study from Brigham and Women's Hospital, a founding member of the Mass General Brigham healthcare system, compared the risk of birth defects in OUD patients who are treated with buprenorphine and methadone during pregnancy. Their findings, published in JAMA Internal Medicine, show buprenorphine is associated with a slightly lower risk of malformations overall compared to methadone, but the authors emphasize the importance ensuring continued access to both treatments during pregnancy and the postpartum period.
"Treatment of OUD with either buprenorphine of methadone in pregnancy is strongly recommended to avoid the life threatening effects of untreated OUD," said author Krista Huybrechts, MS, PhD, of the Division of Pharmacoepidemiology in the Department of Medicine. "Evidence has been accumulating that the use of buprenorphine during pregnancy compared to methadone is associated with better neonatal outcomes, including most congenital defects. This should, however, not be taken to suggest that methadone should not be used in pregnancy. The comparative safety is one factor that should inform the treatment decision."
From 2010 to 2017, the percentage of births affected by OUD increased by 131% from 2010 to 2017. According to the Centers for Disease Control, opioid exposure during pregnancy poses a threat to the health of both mothers and babies, and has been linked to maternal death, poor fetal growth, preterm birth, stillbirth, birth defects and more. Medications for opioid use disorder, including methadone and buprenorphine, can help decrease these risks, but, prior to this study, data on the rates of malformations among infants exposed to these medications in pregnancy were extremely sparse. The few studies available had suggested either no difference in risk or a lower risk for buprenorphine compared to methadone.
The new study's results provide much more precise estimates. The study cohort included 9,514 publicly insured pregnancies with first trimester buprenorphine exposure and 3,846 with methadone exposure. The risk of malformations overall was 50.9 per 1000 pregnancies for buprenorphine and 60.6 per 1000 pregnancies for methadone. Buprenorphine was associated with a slightly lower risk of malformations overall compared to methadone-this 18% reduction in relative risk translates to 1 less event per 100 patients treated with buprenorphine compared to methadone. The risk for several malformation subtypes was lower as well among pregnant individuals treated with buprenorphine compared to methadone, except for gastrointestinal malformations.
The authors note that there are limitations to using Medicaid data to assess the comparative safety of the two medications during pregnancy and their results may be missing MOUD treatment that was not reimbursed by Medicaid. Still, the study offers insights that may help clinicians and expectant mothers who are weighing many considerations during pregnancy.
"I cannot emphasize enough that any opioid agonist therapy - either buprenorphine or methadone - is strongly recommended over untreated OUD during pregnancy," said Huybrechts. "The ultimate goal is to ensure continued access to effective treatment for a given patient during pregnancy as well as the postpartum period. Ensuring continued treatment requires a careful trade-off between comparative safety and other determining factors. The small increase in the risk of malformations with methadone use compared to buprenorphine we observed likely does not exclude methadone as the best treatment choice for some pregnant individuals, particularly those on stable treatment prior to pregnancy or patients who do not respond well to buprenorphine."
Authorship: The lead author of the paper is Elizabeth A Suarez, a former postdoctoral fellow in the Division of Pharmacoepidemiology at BWH and a current instructor of Epidemiology at Rutgers University. Additional authors include Brian T Bateman, Loreen Straub (BWH), Sonia Hernandez-Diaz, Hendrée E. Jones, Kathryn J Gray, Hilary S Connery, Jonathan M. Davis, Barry Lester, Mishka Terplan, Yanmin Zhu (BWH), Seanna M Vine (BWH), and Helen Mogun (BWH).
Disclosures: Connery reports work as a consultant to Alosa Health. Gray received payment from Aetion Inc., Illumina, Roche, and BillionToOne as a consultant for unrelated work. Hernandez-Diaz reports money paid to her institution by Takeda for unrelated work. She received payment from UCB as a consultant for unrelated work. Huybrechts reports money paid to her institution by UCB for unrelated work.
Funding: This study was supported by the US National Institute on Drug Abuse (R01 DA049822).
Paper cited: Suarez E. et al. "First Trimester Use of Buprenorphine or Methadone and the Risk of Congenital Malformations." JAMA Internal Medicine. DOI: 0.1001/jamainternmed.2023.6986
