Buprenorphine Less Risky for Most Birth Defects Than Methadone

Derick Alison
Derick Alison
8 Min Read

The risk of congenital malformations appears to be lower with buprenorphine than with methadone when taken during the first trimester of pregnancy for opioid use disorder (OUD), according to an analysis of Medicaid data.

In the buprenorphine group, risk of congenital malformations was 50.9 out of 1,000 pregnancies compared with 60.6 per 1,000 in the methadone group, Elizabeth Suarez, PhD, MPH, of Brigham and Women’s Hospital and Harvard Medical School in Boston, and colleagues reported in JAMA Internal Medicine.

After adjustment for confounding, that translated to an 18% reduced risk of congenital malformations with buprenorphine (95% CI 0.69-0.97), they found.

“Based on these results, buprenorphine may result in lower risk to the baby, and may be the appropriate treatment option for patients initiating medication for opioid use disorder in pregnancy,” Suarez told MedPage Today in an email.

Still, the team noted that either treatment is “strongly recommended over untreated OUD during pregnancy, which is associated with adverse outcomes due to withdrawal, return to opioid use, overdose, intravenous drug use, and inadequacy of prenatal care.”

“The small increase observed in the risk of malformations with methadone use compared with buprenorphine 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,” the researchers noted.

Suarez told MedPage Today that before doing this study, researchers “had very little information on the risk of birth defects after use of buprenorphine or methadone in pregnancy.” While both medications are used to treat OUD, buprenorphine is a partial μ-opioid receptor agonist with low intrinsic activity while methadone is a full μ-opioid receptor agonist with high intrinsic activity.

To get a better understanding of the risks, the researchers analyzed Medicaid data from 2000 to 2018, totaling 9,514 pregnancies with first-trimester buprenorphine exposure (mean maternal age 28.4) and 3,846 pregnancies with methadone exposure in that timeframe (mean age 28.8).

They excluded pregnancies with chromosomal abnormalities or teratogen exposure within the first trimester, or pregnancies with exposure to the opposite drug in the 3 months before the last menstrual period.

In adjusted analyses, buprenorphine also had a lower risk than methadone for cardiac malformations (RR 0.63, 95% CI 0.47-0.85), including both ventricular septal defect (RR 0.62, 95% CI 0.39-0.98) and secundum atrial septal defect/non-prematurity-related patent foramen ovale (RR 0.54, 95% CI 0.30-0.97).

The same was true for clubfoot (RR 0.55, 95% CI 0.32-0.94), and there was a non-significant trend for oral clefts (RR 0.65, 95% CI 0.35-1.19).

Suarez and colleagues noted that no meaningful conclusions can be drawn about neural tube defects, however, “due to the small number of events and resulting wide confidence intervals.”

As for secondary organ system-specific malformations, there was a lower risk of central nervous system, urinary, and limb malformations with buprenorphine, but the drug appeared to carry a greater risk of gastrointestinal malformations (RR 1.98, 95% CI 1.15-3.39).

Two invited commentaries accompanied the research, including one by Cara Poland, MD, MEd, of Henry Ford Health in Grand Rapids, and colleagues, which said the study “adds to the growing research base supporting buprenorphine as the preferred approach for beginning treatment in pregnant populations in the absence of any other considerations.”

However, Poland and colleagues cautioned that the study didn’t include population-level rates of congenital defects “that would have better represented the safety of [medications for OUD] MOUD instead of simply comparing 2 medications with long-standing safety data.”

“Moreover, while the risk reduction in this study was statistically significant, the differences are small and do not necessitate adjusting MOUD during pregnancy based on this alone,” they added. “When a patient starts taking MOUD during pregnancy, it is important that practitioners understand the patient’s individual needs, access to MOUD, and comfort with different approaches, and carefully weigh the potential benefits of changing medications relative to the possible drawbacks, including disruption to ongoing and well-managed OUD, with their patients.”

Indeed, a second editorial by Max Jordan Nguemeni Tiako, MD, MS, of Brigham and Women’s Hospital in Boston, and colleagues noted that the study found “a 1% absolute risk reduction of congenital malformations” with buprenorphine compared with methadone.

Tiako and colleagues noted that the study population is a “relatively stable group of patients with OUD … excluding a substantial number of chronically underinsured and uninsured individuals,” and urged caution in extrapolating to “newly pregnant individuals with untreated OUD.”

“As fentanyl contaminates a growing proportion of the drug supply, patients with OUD are experiencing more difficulty initiating and remaining stable on buprenorphine, and for those, methadone may be a more effective option,” they wrote.

They also emphasized that the “ultimate treatment decision must be the result of shared decision-making between a knowledgeable clinician and the patient, rather than promoting one medication over another.”

  • author['full_name']

    Rachael Robertson is a writer on the MedPage Today enterprise and investigative team, also covering OB/GYN news. Her print, data, and audio stories have appeared in Everyday Health, Gizmodo, the Bronx Times, and multiple podcasts. Follow

Disclosures

The research was funded in part by the National Institute on Drug Abuse.

Co-authors reported relationships with Takeda, UCB, Janssen, Moderna, UCB, BillionToOne, Aetion, Illumina, Roche, and Alosa Health.

The editorialists reported no relevant financial disclosures.

Primary Source

JAMA Internal Medicine

Source Reference: Suarez E, et al “First trimester use of buprenorphine or methadone and the risk of congenital malformations” JAMA Intern Med 2024; DOI: 10.1001/jamainternmed.2023.6986.

Secondary Source

JAMA Internal Medicine

Source Reference: Nguemeni Tiako MJ, et al “Prenatal opioid use disorder treatment — the importance of shared decision-making” JAMA Intern Med 2024; DOI: 10.1001/jamainternmed.2023.6976.

Additional Source

JAMA Internal Medicine

Source Reference: Poland C, et al “Medication for the treatment of opioid use disorder in pregnancy is essential” JAMA Intern Med 2024; DOI: 10.1001/jamainternmed.2023.6977.

Additional Source

JAMA Interal Medicine

Source Reference: Grady D “The importance of treating opioid use disorder in pregnancy” JAMA Intern Med 2024; DOI: 10.1001/jamainternmed.2023.7272.

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