Buprenorphine safer than methadone for opioid use disorder during pregnancy: JAMA

The study, published in JAMA Internal Medicine, suggests that malformation risk is one factor that informs the individualized patient decision regarding medications for opioid use disorder in pregnancy.

The cohort study of 9514 pregnancies with first-trimester buprenorphine exposure and 3846 with methadone exposure revealed lower prevalence of congenital malformations overall and several malformation subtypes among pregnant women treated with buprenorphine versus methadone, except for gastrointestinal malformations.

Overall, there was an 18% relative risk reduction for malformations, translating to 1 less event per 100 patients treated with buprenorphine vs methadone.

Methadone or buprenorphine is used for treating opioid use disorder in pregnancy; however, a lack of knowledge exists on their teratogenic potential. To fill this knowledge gap, Elizabeth A. Suarez, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, and colleagues aimed to compare the risk of congenital malformations following in-utero exposure to buprenorphine vs methadone.

For this purpose, the researchers used healthcare utilization data from publicly insured Medicaid beneficiaries in the US from 2000 to 2018. It included 13 360 pregnancies with enrollment from 90 days before pregnancy starts through 1 month after delivery and first-trimester use of buprenorphine or methadone linked to infants. The exposure was a pharmacy dispensing of buprenorphine or a code for methadone administration in the first trimester.

The study's primary outcomes were major malformations overall and malformations previously associated with opioids (any cardiac malformations, secundum atrial septal defect/nonprematurity-related patent foramen ovale, ventricular septal defect, neural tube defects, oral clefts, and clubfoot). Secondary outcomes included other organ system–specific malformations.

Risk differences and risk ratios (RRs) were estimated by comparing buprenorphine with methadone, after adjustment for confounders with propensity score overlap weights.

The cohort included 9514 pregnancies with first-trimester buprenorphine exposure (mean maternal age, 28.4 years) and 3846 with methadone exposure (mean maternal age, 28.8 years).

The study led to the following findings:

• The risk of malformations overall was 50.9 per 1000 pregnancies for buprenorphine and 60.6 per 1000 pregnancies for methadone.
• After confounding adjustment, buprenorphine was associated with a lower risk of malformations compared with methadone (RR, 0.82).
• The risk was lower with buprenorphine for cardiac malformations (RR, 0.63), including both ventricular septal defect (RR, 0.62) and secundum atrial septal defect/non-prematurity-related patent foramen ovale (RR, 0.54), oral clefts (RR, 0.65), and clubfoot (RR, 0.55).
• Results for neural tube defects were uncertain given low event counts.
• In secondary analyses, buprenorphine was associated with a reduced risk of central nervous system, urinary, and limb malformations but a greater risk of gastrointestinal malformations compared with methadone. These findings were consistent in sensitivity and bias analyses.

"When determining the optimal treatment for pregnant women with opioid use disorder, considerations should include the relative risk reduction for malformations overall with methadone versus buprenorphine, as well as previous success on a particular treatment, treatment access, and the likelihood of retention in treatment" the researchers concluded.

Reference

Suarez EA, Bateman BT, Straub L, et al. First Trimester Use of Buprenorphine or Methadone and the Risk of Congenital Malformations. JAMA Intern Med. Published online January 22, 2024. doi:10.1001/jamainternmed.2023.6986