REVIEW OF: Suarez EA et al, N Engl J Med 2022;387(22):2033–2044

STUDY TYPE: Cohort review

Ever since the seminal MOTHER trial, buprenorphine and methadone have been the gold-standard treatments of opioid use disorder (OUD) during pregnancy. But the two agents are not necessarily equivalent, with buprenorphine being associated with milder neonatal withdrawal syndrome (NOWS) and reduced hospital stays (Jones HE et al, N Engl J Med 2010;363(24):2320–2331). Despite its significance, the MOTHER trial was fairly limited in scope, with just 175 participants. To validate the findings in a much larger group of patients, researchers utilized a Medicaid database of over 2.5 million pregnancies, nearly 16,000 of which were exposed to buprenorphine or methadone.

The researchers found that buprenorphine-exposed newborns had significantly better outcomes than those exposed to methadone, with a lower risk of NOWS (52.0% vs 69.2%, relative risk [RR]=0.73, 95% confidence interval [CI]=0.73–0.75), preterm birth (14.4% vs 24.9%, RR=0.58, 95% CI=0.53–0.62), small size for gestational age (12.1% vs 15.3%, RR=0.72, 95% CI=0.66–0.80), and low birth weight (8.3% vs 14.9%, RR=0.56, 95% CI=0.50–0.63). On the other hand, parental outcomes did not differ in rates of cesarean section delivery, and severe pregnancy complications were similar between the two groups.

Limitations of this study derive mostly from its design as a retrospective cohort study; we don’t know how patient outcomes might compare to those of patients with untreated OUD. We also lack data that might influence the results, such as medication dose, parental lifestyle, and behavioral factors. All the information came from a Medicaid database, which has variable coverage across states, potentially influencing which patients were included.

Carlat Take

This large retrospective cohort study makes a compelling argument for treating OUD with buprenorphine over methadone during pregnancy, at least in terms of neonatal outcomes. Parental adverse outcomes were comparable. Although there was no placebo group, treatment with either medication is certainly better than no treatment. Therefore, treat all pregnant OUD patients with opioid agonist treatment, and all else being equal, lean toward buprenorphine over methadone.