Pregnant patients with opioid use disorder (OUD) are strongly encouraged to receive medication treatment with either buprenorphine or methadone. Medications for OUD (MOUD) reduce the risks related to untreated OUD while pregnant, including antagonistic outcomes because of withdrawal, return to opioid use, overdose, intravenous drug use, and inadequacy of prenatal care. So far, there was very sparse data on the reproductive safety of buprenorphine and methadone. 

A recent study from Suarez and colleagues compares the danger of congenital malformations following first trimester exposure to buprenorphine and methadone. The researchers analyzed data from publicly insured Medicaid beneficiaries within the US between 2000 and 2018. On this cohort, a complete of 13,360 pregnancies with first trimester use of either buprenorphine or methadone were identified and linked to infant medical records. Rates of major malformations overall and specific malformations previously related to opioid exposure (cardiac malformations, neural tube defects, clubfoot, and oral clefts) were assessed. 

The cohort included 9,514 pregnancies with first-trimester buprenorphine exposure (mean [SD] maternal age, 28.4 [4.6] years) and three,846 with methadone exposure (mean [SD] maternal age, 28.8 [4.7] years). The chance of malformations overall was 50.9 per 1000 pregnancies for buprenorphine and 60.6 per 1,000 pregnancies for methadone. After adjusting for confounding aspects, buprenorphine was related to a lower risk of malformations compared with methadone (RR, 0.82; 95% CI, 0.69-0.97). With regard to specific malformations, risk was lower with buprenorphine for 

• Cardiac malformations (RR, 0.63; 95% CI, 0.47-0.85), 
• Oral clefts (RR, 0.65; 95% CI, 0.35-1.19), and 
• Clubfoot (RR, 0.55; 95% CI, 0.32-0.94).

In secondary analyses, buprenorphine was related to a lower risk of central nervous system, urinary, and limb malformations but a greater risk of gastrointestinal malformations in comparison with methadone. 

Clinical Implications

In this massive cohort study analyzing data from publicly insured Medicaid beneficiaries, the general risk of malformations was lower with buprenorphine than with methadone. Furthermore, the danger of most malformations previously related to opioid exposure, including cardiac defects, oral clefts, and clubfoot, was lower in buprenorphine-exposed infants in comparison with those exposed to methadone. This study is the most important so far examining the reproductive safety of buprenorphine and methadone and provides vital information to patients and their providers.

While risk of malformation is one vital factor informing decisions regarding using medications for opioid use disorder while pregnant, it is just not the one factor. Whatever treatment is chosen, it can be crucial to emphasise that the “best” treatment is the one which reduces the danger of opioid use while pregnant. 

Although this study indicates that buprenorphine can have a lower risk of malformations than methadone, this finding doesn’t preclude using methadone while pregnant. For some pregnant patients, particularly those on stable treatment with methadone prior to pregnancy or patients who don’t respond well to buprenorphine, methadone often is the best treatment selection.

The last word goal is to make sure continued access to effective MOUD while pregnant and the postpartum period. One must consider information regarding reproductive safety, in addition to other aspects including access to a specific treatment, patient preference, treatment response, and the likelihood of retention in treatment.

Ruta Nonacs, MD PhD

References

Suarez EA, Bateman BT, Straub L, Hernández-Díaz S, Jones HE, Gray KJ, Connery HS, Davis JM, Lester B, Terplan M, Zhu Y, Vine SM, Mogun H, Huybrechts KF. First Trimester Use of Buprenorphine or Methadone and the Risk of Congenital Malformations. JAMA Intern Med. 2024 Jan 22: e236986.