Buprenorphine may be safer than methadone for opioid use disorder in pregnancy

New data published in The New England Journal of Medicine showed that buprenorphine use during pregnancy was associated with a lower risk for adverse neonatal outcomes compared with methadone use.

However, both opioid use disorder (OUD) treatments were associated with a similar risk for adverse maternal outcomes.

“Our results may encourage increasing access to buprenorphine treatment specifically among pregnant people,” Elizabeth A. Suarez, PhD, MPH, a pharmacoepidemiologist at the Center for Pharmacoepidemiology and Treatment Science at the Rutgers Institute for Health, Health Care Policy and Aging Research, said in a press release. “It’s essential for the general public to understand the importance of [OUD] treatment during pregnancy to avoid harms associated with lack of treatment.”

According to Suarez and colleagues, OUD has steadily increased among pregnant patients over the past 2 decades. As of 2017, an estimated 8.2 per 1,000 deliveries in the United States were affected by OUD.

In August 2017, the American College of Obstetricians and Gynecologists and the American Society of Addiction Medicine expanded their treatment guidelines for OUD in pregnancy to include buprenorphine. Until then, only methadone was recommended by these organizations.

There are important differences between buprenorphine and methadone, Suarez and colleagues wrote.

“Methadone is a full agonist with high intrinsic activity at mu-opioid receptors, whereas buprenorphine is a high-affinity partial agonist with low intrinsic activity,” they wrote. “Methadone is administered during daily in-person visits to federally regulated opioid treatment programs. Buprenorphine can be prescribed by approved providers, which allows patients to administer the medication themselves.”

Previous research has linked buprenorphine to more favorable maternal and neonatal outcomes, but the data are limited, according to Suarez and colleagues. To learn more, the researchers conducted a cohort study to compare maternal and neonatal outcomes of patients exposed to buprenorphine vs. methadone during pregnancy. They used data from patients who were enrolled in public insurance programs in the United States from 2000 to 2018, using propensity-score overlap weights to adjust risk ratios for confounders.

The analysis included 2,548,372 pregnancies that ended in live births. Among the pregnant patients, 10,704 were exposed to buprenorphine and 4,387 were exposed to methadone in early pregnancy (up to gestational week 19), while 11,272 were exposed to buprenorphine and 5,056 were exposed to methadone in late pregnancy (gestational week 20 up to the day before delivery). In the latter group, 9,976 pregnant patients were exposed to buprenorphine and 4,597 were exposed to methadone in the 30 days before delivery.

Suarez and colleagues reported that 52% of infants who were exposed to buprenorphine 30 days before delivery experienced neonatal abstinence syndrome vs. 69.2% of those exposed to methadone (adjusted RR [aRR] = 0.73; 95% CI, 0.71-0.75).

In early pregnancy, buprenorphine exposure was associated with lower risks compared with methadone exposure for:

• preterm birth (14.4% vs. 24.9%; aRR = 0.58; 95% CI, 0.53-0.62);
• small size for gestational age (12.1% vs. 15.3%; aRR = 0.72; 95% CI, 0.66-0.8); and
• low birth weight (8.3% vs. 14.9%; aRR = 0.56; 95% CI, 0.5-0.63).

The researchers observed similar rates of delivery by cesarean section among patients exposed to buprenorphine vs. methadone in early pregnancy (33.6% vs. 33.1%; aRR = 1.02; 95% CI, 0.97-1.08), as well as similar rates of severe maternal complications (3.3% vs. 3.5%; aRR = 0.91; 95% CI, 0.74-1.13).

The results of buprenorphine and methadone exposure in late pregnancy were consistent with those in early pregnancy, according to Suarez and colleagues.

Although buprenorphine was associated with more favorable neonatal outcomes, the researchers wrote that “any opioid agonist therapy is recommended over untreated opioid use disorder during pregnancy, because untreated persons have greater incidence of adverse outcomes owing to withdrawal, return to opioid use, overdose, intravenous drug use, and inadequacy of prenatal care.”

“These results may guide clinical recommendations for people with opioid use disorder who are pregnant or are hoping to be pregnant,” Suarez said in the release.

In a related editorial, Elizabeth E. Krans, MD, MSc, an associate professor in the department of obstetrics, gynecology and reproductive sciences at the University of Pittsburgh, and of the Magee-Womens Research Institute in Pittsburgh, noted that buprenorphine is the most commonly used OUD medication during pregnancy, and the study reinforces its role as a first-line treatment option for pregnant patients with OUD. However, she also said that buprenorphine use “has become more challenging with the escalation of the use of synthetic opioids such as fentanyl.”

“A partial mu-opioid receptor agonist, buprenorphine may insufficiently mitigate opioid cravings and precipitate withdrawal in patients who use fentanyl, which is 50 to 100 times more potent than morphine,” Krans wrote. “Thus, the choice to use methadone or buprenorphine during pregnancy should be the result of a shared decision-making process between a patient and a provider that incorporates factors such as patient preference, previous treatment experiences, and medication availability.”

References:

Buprenorphine, not methadone, may be safer treatment for opioid use disorder during pregnancy. https://www.rutgers.edu/news/buprenorphine-not-methadone-may-be-safer-treatment-opioid-use-disorder-during-pregnancy. Published Nov. 30, 2022. Accessed Nov. 30, 2022.

Krans EF. N Engl J Med. 2022;doi:10.1056/NEJMe2212967.

Suarez EA, et al. N Engl J Med. 2022;doi:10.1056/NEJMoa2203318.