The occurrence of opioid use disorder among pregnant persons in the US has increased steadily since 2000 to the present. Currently, there are an estimated 8.2 and 14.6 per 1000 deliveries affected, respectively for those with or without Medicaid insurance. Medicaid is a public insurance program available to low-income women in the United States. Those without Medicaid lacked insurance and faced more opioid use challenges. The standard treatment for pregnant women with opioid use disorder is buprenorphine or methadone. These drugs are associated with improved adherence to prenatal care, lower incidence of preterm birth, reduced return to opioid use, fewer instances of opioid overdose, and less deaths from opioid overdose. Methadone is administered during daily in-person visits while buprenorphine can be prescribed by approved providers allowing patients to take the drug on their own. In addition, various local and state regulations impact the use of these compounds by different health care facilities.
Data on maternal outcomes tied to these drugs are limited. A recent research study aimed to assess the risks of adverse neonatal and maternal outcomes with buprenorphine compared to methadone in pregnancy with careful control for confounders.
Who was involved in the study
Among a national database of over 2.5 million pregnancies ending in live births, 10,704 pregnant persons had been exposed to buprenorphine and 4,387 to methadone in early pregnancy. The sizes of the groups were similar in late pregnancy. A high degree of ongoing treatment was observed during pregnancy, with most pregnant persons having evidence of exposure to their medication 30 days before delivery.
Pregnant persons who received buprenorphine were more likely to be white, from the Northeast or Midwest, and living in non-metropolitan or rural areas than those who received methadone. They also had a higher prevalence of depression and anxiety diagnoses, as well as documented non-opioid substance use disorders. Antidepressants and other psychotropic medications were more common among those who received buprenorphine, while prescription opioid agents were more common in the methadone group. Most other characteristics and complications of opioid use disorders were similar between both groups.
Neonatal abstinence syndrome (a drug withdrawal condition that can happen when opioids are stopped abruptly during pregnancy; the condition can result in harm to the fetus being carried by the mother) occurred in 69% of infants exposed to methadone and 52% of those exposed to buprenorphine in the 30 days before delivery. Connections were also observed between buprenorphine exposure (as compared with methadone exposure) and decreased chance of preterm birth, small size for gestational age, and low birth weight regardless of whether exposure occurred in early or late pregnancy. Risks of adverse maternal outcomes were similar among persons who received buprenorphine and those who received methadone.
Results
This study of Medicaid beneficiaries found strong connections between buprenorphine use in pregnancy and less neonatal abstinence syndrome, preterm birth, small size for gestational age, and low birth weight. Adjusting the study data to account for other factors that could explain the outcomes did not change the results – making the data more likely to be true. No association was found between buprenorphine or methadone use and cesarean section and severe maternal complications.
This study’s results support those of a prior research study called the MOTHER (Maternal Opioid Treatment: Human Experimental Research) trial, which found that buprenorphine use during pregnancy leads to more favorable outcomes for infants than methadone exposure. The possible pharmacologic explanation is that buprenorphine is a partial agonist (mimicker of opioids) while methadone is a full agonist (replicates action of opioids that are cause of opioid use disorder).
Limitation
One potential limitation of this current research is that pregnant individuals could have been taking drugs that were not documented by the researchers. However, this factor was studied by the research team and determined to not have a meaningful effect on results, as switching therapy during pregnancy was uncommon. Also, if switching occurred, it would have likely been expected to be from buprenorphine to methadone – the compounds being studied.
Conclusion
Buprenorphine or methadone therapy is recommended over untreated opioid use disorder during pregnancy due to greater occurrence of adverse outcomes, and results from this large national database study indicated that buprenorphine treatment for opioid use disorder was associated with more favorable neonatal outcomes than methadone treatment.
