Combination OUD Treatment Safe During Pregnancy

For pregnant persons with opioid use disorder (OUD), buprenorphine and naloxone used together were associated with similar or better neonatal and maternal outcomes versus buprenorphine alone, a large nationwide population-based cohort study found.

Among Medicaid-insured pregnant persons and their linked infants, researchers led by Loreen Straub, MD, of Brigham and Women’s Hospital and Harvard Medical School in Boston, observed lower risks for neonatal abstinence syndrome (NAS), neonatal intensive care unit (NICU) admissions, and small for gestational age for those exposed to the combination treatment:

• NAS: 37.4% vs 55.8% with buprenorphine alone (weighted relative risk [RR] 0.77, 95% CI 0.70-0.84)
• NICU admissions: 30.6% vs 34.9% (weighted RR 0.91, 95% CI 0.85-0.98)
• Small for gestational age: 10% vs 12.4% (weighted RR 0.86, 95% CI 0.75-0.98)

Furthermore, they found similar rates for maternal morbidity with the combination treatment compared with buprenorphine alone, and “no differences were observed with respect to major congenital malformations overall, low birth weight, preterm birth, respiratory symptoms, or cesarean delivery,” the authors wrote in JAMA.

“Buprenorphine combined with naloxone during pregnancy appears to be a safe treatment option,” Straub and team concluded. “This supports the view that both formulations are reasonable options for treatment of OUD in pregnancy, affirming flexibility in collaborative treatment decision-making.”

Methadone has been used for treating OUD in pregnancy since the 1970s; however, buprenorphine’s use is now likely “equal to or even higher than methadone,” following a landmark 2010 randomized trial, which found that neonatal outcomes with buprenorphine were similar to — and in certain cases, superior to — methadone for OUD in pregnancy, wrote Straub and co-authors.

Co-author Brian T. Bateman, MD, MSc, of Stanford University School of Medicine in California, told MedPage Today that “our data really point to the idea that the [combination] product is as safe, and potentially, in some situations, results in better outcomes than buprenorphine alone.”

“This is fantastic, as there has always been this question as to whether the combination was safe in pregnancy,” Gail D’Onofrio, MD, of the Yale School of Public Health in New Haven, Connecticut, who was not affiliated with the research, told MedPage Today.

Adding naloxone to buprenorphine may help deter intranasal or intravenous diversion. In addition, pregnant patients stable on combination formulations may be reluctant to switch. In such cases, these findings suggest “it might be a very reasonable thing to just continue the patients on that medication, rather than attempting to switch them to the mono-product,” Bateman noted.

For this study, Straub and team used healthcare utilization data from Medicaid-insured beneficiaries from 2000 to 2018. The cohort was limited to the 9,537 pregnant persons linked to their liveborn infants, with maternal Medicaid enrollment from 3 months before pregnancy to 1 month after delivery and infant enrollment for the first 3 months after birth, unless they died sooner.

Researchers excluded pregnancies with chromosomal anomalies and exposure to known teratogens or methadone during the first trimester.

This included 3,369 pregnant persons exposed to buprenorphine with naloxone during the first trimester (mean age 28.8 years) and 5,326 exposed to buprenorphine alone or who switched from the combination to buprenorphine alone by the end of the first trimester (mean age 28.3 years). Analyses for malformation outcomes and neonatal abstinence syndrome were restricted to smaller subsets of infants.

The groups were mostly well-balanced, the authors said, but the combination treatment group was more likely to be from the South, to have delivered in earlier years, to use other medications such as antidepressants and benzodiazepines, and to have inadequate prenatal care. They were also less likely to misuse other substances.

On propensity-score weighted analyses, no significant differences were observed for severe maternal morbidity with the combination treatment compared with buprenorphine alone (crude 2.6% vs 2.9%, respectively), major congenital malformations (5.2% vs 5%), cardiac malformations (1.5% vs 1.3%), low birth weight (8.5% vs 7.6%), preterm birth (14.9% vs 13.1%), respiratory symptoms (12.7% vs 11.3%), or cesarean delivery (34.9% vs 32.7%).

Straub and colleagues noted that results were mostly unchanged when looking at subgroups defined by typical treatment patterns, as well as in sensitivity analyses, including when limiting to those with exposure throughout pregnancy.

A limitation of the study was that potential confounders, such as alcohol use and cigarette smoking, may have been under-recorded in claims data.

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