Opioid Use Disorder in Pregnancy

The prevalence of opioid use disorder among pregnant persons has increased steadily. The standard care for treating pregnant persons with opioid use disorder is opioid agonist therapy with buprenorphine or methadone, which is associated with improved adherence to prenatal care, lower incidence of preterm birth, reduced return to opioid use, and fewer instances of opioid overdose and death from opioid overdose. Buprenorphine and methadone have important differences. 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. 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.

Study Overview

The goal of the current study by E.A. Suarez et al was to assess the risks of adverse neonatal and maternal outcomes associated with the use of buprenorphine as compared with methadone in pregnancy in a large U.S. cohort in which there was careful control for confounders.

Authors conducted a cohort study involving pregnant persons who were enrolled in public insurance programs in the United States during the period from 2000 through 2018 in which they examined outcomes among those who received buprenorphine as compared with those who received methadone. Exposure to the two medications was assessed in early pregnancy (through gestational week 19), late pregnancy (gestational week 20 through the day before delivery), and the 30 days before delivery. Risk ratios for neonatal and maternal outcomes were adjusted for confounders with the use of propensity-score overlap weights.

The data source for the study consisted of 2,548,372 pregnancies that ended in live births. In early pregnancy, 10,704 pregnant persons were exposed to buprenorphine and 4,387 to methadone. In late pregnancy, 11,272 were exposed to buprenorphine and 5,056 to methadone (9,976 and 4,597, respectively, in the 30 days before delivery).

Key Findings

• Neonatal abstinence syndrome occurred in 52.0% of the infants who were exposed to buprenorphine in the 30 days before delivery as compared with 69.2% of those exposed to methadone (adjusted relative risk, 0.73).
• Preterm birth occurred in 14.4% of infants exposed to buprenorphine in early pregnancy and in 24.9% of those exposed to methadone (adjusted relative risk, 0.58).
• Small size for gestational age in 12.1% and 15.3%, respectively (adjusted relative risk, 0.72).
• Low birth weight in 8.3% and 14.9% (adjusted relative risk, 0.56).
• Delivery by cesarean section occurred in 33.6% of pregnant persons exposed to buprenorphine in early pregnancy and 33.1% of those exposed to methadone (adjusted relative risk, 1.02).
• Severe maternal complications developed in 3.3% and 3.5%, respectively (adjusted relative risk, 0.91).

Results of exposure in late pregnancy were consistent with results of exposure in early pregnancy.

Conclusion

In this cohort study that drew from a large database of Medicaid beneficiaries, we observed strong inverse associations between buprenorphine use in pregnancy (as compared with methadone use) and neonatal abstinence syndrome, preterm birth, small size for gestational age, and low birth weight. Adjustment for an extensive list of measured confounders did not meaningfully change the estimates. No association was found between the use of buprenorphine or methadone and cesarean section and severe maternal complications. Sensitivity analyses that targeted exposure and outcome misclassification as well as unmeasured confounding did not change the interpretation of the findings.

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. Results of our study using a large, national database of Medicaid beneficiaries showed that buprenorphine treatment for opioid use disorder during pregnancy was associated with more favorable neonatal outcomes than methadone treatment.

The use of buprenorphine in pregnancy was associated with a lower risk of adverse neonatal outcomes than methadone use; however, the risk of adverse maternal outcomes was similar among persons who received buprenorphine and those who received methadone. (Funded by the National Institute on Drug Abuse.)