Buprenorphine use in pregnancy associated with lower risk of adverse neonatal outcomes than methadone: NEJM
The prevalence of opioid use disorder among pregnant personshas increased steadily. The standard care for treating pregnant persons withopioid use disorder is opioid agonist therapy with buprenorphine or methadone,which is associated with improved adherence to prenatal care, lower incidenceof preterm birth, reduced return to opioid use, and fewer instances of opioidoverdose and death from opioid overdose. Buprenorphine and methadone haveimportant differences. Methadone is a full agonist with high intrinsic activityat mu-opioid receptors, whereas buprenorphine is a high-affinity partialagonist with low intrinsic activity. Methadone is administered during dailyin-person visits to federally regulated opioid treatment programs.Buprenorphine can be prescribed by approved providers, which allows patients toadminister the medication themselves.
The goal of the current study by E.A. Suarez et al was toassess the risks of adverse neonatal and maternal outcomes associated with theuse 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 personswho were enrolled in public insurance programs in the United States during theperiod from 2000 through 2018 in which they examined outcomes among those whoreceived buprenorphine as compared with those who received methadone. Exposureto the two medications was assessed in early pregnancy (through gestationalweek 19), late pregnancy (gestational week 20 through the day before delivery),and the 30 days before delivery. Risk ratios for neonatal and maternal outcomeswere adjusted for confounders with the use of propensity-score overlap weights.
The data source for the study consisted of 2,548,372pregnancies that ended in live births. In early pregnancy, 10,704 pregnantpersons were exposed to buprenorphine and 4387 to methadone. In late pregnancy,11,272 were exposed to buprenorphine and 5056 to methadone (9976 and 4597,respectively, in the 30 days before delivery).
Neonatal abstinence syndrome occurred in 52.0% of theinfants who were exposed to buprenorphine in the 30 days before delivery ascompared with 69.2% of those exposed to methadone (adjusted relative risk, 0.73).
Preterm birth occurred in 14.4% of infants exposed tobuprenorphine 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% and15.3%, respectively (adjusted relative risk, 0.72); and low birth weight in8.3% and 14.9% (adjusted relative risk, 0.56). Delivery by cesarean sectionoccurred in 33.6% of pregnant persons exposed to buprenorphine in earlypregnancy and 33.1% of those exposed to methadone (adjusted relative risk, 1.02),and severe maternal complications developed in 3.3% and 3.5%, respectively(adjusted relative risk, 0.91). Results of exposure in late pregnancy wereconsistent with results of exposure in early pregnancy.
In this cohort study that drew from a large database ofMedicaid beneficiaries, we observed strong inverse associations betweenbuprenorphine use in pregnancy (as compared with methadone use) and neonatalabstinence syndrome, preterm birth, small size for gestational age, and lowbirth weight. Adjustment for an extensive list of measured confounders did notmeaningfully change the estimates. No association was found between the use ofbuprenorphine or methadone and cesarean section and severe maternalcomplications. Sensitivity analyses that targeted exposure and outcomemisclassification as well as unmeasured confounding did not change theinterpretation of the findings.
Any opioid agonist therapy is recommended over untreatedopioid use disorder during pregnancy, because untreated persons have greaterincidence of adverse outcomes owing to withdrawal, return to opioid use,overdose, intravenous drug use, and inadequacy of prenatal care.6 Results ofour study using a large, national database of Medicaid beneficiaries showedthat buprenorphine treatment for opioid use disorder during pregnancy wasassociated with more favorable neonatal outcomes than methadone treatment.
The use of buprenorphine in pregnancy was associated with alower risk of adverse neonatal outcomes than methadone use; however, the riskof adverse maternal outcomes was similar among persons who receivedbuprenorphine and those who received methadone. (Funded by the NationalInstitute on Drug Abuse.)
Source: E.A.Suarez, K.F. Huybrechts, L. Straub, N Engl J Med 2022;387:2033-44. DOI: 10.1056/NEJMoa2203318
