Lower malformation risk with buprenorphine vs. methadone exposure in pregnancy

Key takeaways:

• In utero buprenorphine exposure was associated with lower malformation risks vs. methadone exposure.
• Gastrointestinal malformation risks were greater with buprenorphine vs. methadone.

Infants exposed in utero to buprenorphine had lower risk for malformations associated with opioid exposure compared with methadone-exposed infants, according to cohort study results published in JAMA Internal Medicine.

“It is unknown whether partial agonism at µ-opioid receptors with buprenorphine affects malformation risk,” Elizabeth A. Suarez, PhD, MPH, instructor of epidemiology at the Center for Pharmacoepidemiology and Treatment Science at the Rutgers Institute for Health, Health Care Policy and Aging Research and the department of biostatistics and epidemiology at the Rutgers School of Public Health, and colleagues wrote. “Endogenous opioids are regulators of growth and development and can plausibly affect embryologic development.”

Suarez and colleagues conducted a population-based cohort study using health care utilization data on 13,360 pregnancies from publicly insured U.S. Medicaid beneficiaries from 2000 to 2018. All pregnancies were enrolled from 90 days before pregnancy through 1 month postpartum, and first trimester use of buprenorphine or methadone.

The primary outcomes included major overall malformations and malformations previously associated with opioid use. Secondary outcomes included other organ system-specific malformations.

Overall, 9,514 pregnancies (mean age, 28.4 years) had first trimester buprenorphine exposure, and 3,846 pregnancies (mean age, 28.8 years) had first trimester methadone exposure.

Overall malformation risks were 50.9 per 1,000 pregnancies for buprenorphine-exposed infants and 60.6 per 1,000 pregnancies for methadone-exposed infants. Buprenorphine was associated with a lower malformation risk compared with methadone (RR = 0.82; 95% CI, 0.69-0.97).

Risks for cardiac malformations (RR = 0.63; 95% CI, 0.47-0.85), including ventricular septal defects (RR = 0.62; 95% CI, 0.39-0.98) and secundum atrial septal defects/nonprematurity-related patent foramen ovale (RR = 0.54; 95% CI, 0.32-0.94), oral clefts (RR = 0.65; 95% CI, 0.35-1.19) and clubfoot (RR = 0.55; 95% CI, 0.32-0.94) were all lower for buprenorphine-exposed infants compared with methadone-exposed infants.

In addition, buprenorphine was associated with lower risks for central nervous system (RR = 0.51; 95% CI, 0.3-0.89), urinary (RR = 0.62; 95% CI, 0.37-1.04) and limb malformations (RR = 0.53; 95% CI, 0.34-0.83) compared with methadone. However, buprenorphine was associated with a greater gastrointestinal malformation risk compared with methadone (RR = 1.98; 95% CI, 1.15-3.39). Results remained consistent in sensitivity and bias analyses.

Researchers noted that risks for neural tube defects with exposure to buprenorphine or methadone were uncertain given low event counts.

“The ultimate goal remains to ensure continued access to effective [medications for opioid use disorder] for a given patient during pregnancy as well as the postpartum period; this requires a careful trade-off between comparative safety and other determining factors such as treatment access, patient preference, treatment response and the likelihood of retention in treatment,” the researchers wrote.