Use of buprenorphine during pregnancy better for infants than methadone, study finds

Stanford Medicine and Harvard researchers found that buprenorphine for opioid use disorder treatment during pregnancy was linked to better outcomes for newborns than methadone.

- By Helen Santoro

Researchers found that babies born to mothers who took buprenorphine for opioid use disorder overall had higher birth weight, showed fewer symptoms of opioid withdrawal and were less likely to be born prematurely than those who took methadone.

Infants whose mothers suffered from opioid use disorder and used the drug buprenorphine during pregnancy to treat the condition had better health outcomes than infants exposed to methadone in utero, according to a study by researchers at Harvard University and Stanford Medicine.  

The study, which will be published Dec. 1 in The New England Journal of Medicine, drew from a massive database of pregnant women nationwide who were enrolled in public insurance programs from 2000 to 2018. Of these individuals, the researchers analyzed 21,976 who had opioid use disorder and were given buprenorphine, and 9,443 who were given methadone.

“There is still a lot of variation: Some patients are started on methadone during pregnancy, and some are started on buprenorphine. A lot of it just comes down to the communities where the patients are being treated or the preference of the providers,” said Brian Bateman, MD, the senior author of the study and chair of the Department of Anesthesiology, Perioperative, and Pain Medicine. “There is a need for more data to help inform the treatment of this really important patient population.”

Rising opioid use in pregnancy

Buprenorphine and methadone are both opioid agonists, meaning they activate the opioid receptors in the brain to mimic the effect of the drugs. The two drugs help reduce cravings and prevent the agony of opioid withdrawal, allowing safe recovery from addiction. They have become increasingly vital as the prevalence of opioid use among pregnant women has steadily risen in the United States. As of 2017, around 8.2 per 1,000 babies born in the nation had a mother who was reliant on opioids during her pregnancy. This number is even higher for pregnant women insured by Medicaid: 14.6 per 1,000 deliveries were affected by opioid use. 

Prior research suggested that buprenorphine may lead to better medical outcomes for infants of mothers with opioid use disorder than methadone. Specifically, the Maternal Opioid Treatment Human Experimental Research (MOTHER) trial out of Johns Hopkins University showed that babies exposed to buprenorphine in the uterus required significantly less morphine for the treatment of neonatal abstinence syndrome, a group of symptoms such as fussiness, seizures, vomiting and diarrhea, and sleep problems from drug withdrawal.

Brian Bateman

The Johns Hopkins trial also found that infants exposed to buprenorphine were hospitalized for less time than infants exposed to methadone. However, the study had a relatively small sample size with only 175 participants, 86 of whom received buprenorphine, leaving scientists with many unanswered questions.

In the current study, lead author Elizabeth Suarez, PhD, who was a postdoctoral scholar at Brigham and Women’s Hospital when the study was conducted, assessed exposure to buprenorphine and methadone in early pregnancy (through gestational week 19), late pregnancy (gestational week 20 through the day before delivery) and the 30 days before delivery (when drug exposure affects neonatal abstinence syndrome).  

Results showed that neonatal abstinence syndrome occurred in 52% of infants exposed to buprenorphine in the 30 days before delivery and in 69.2% of those exposed to methadone. Preterm birth, when a baby is born before 37 weeks of pregnancy, occurred in 14.4% of infants exposed to buprenorphine in early pregnancy and in 24.9% of babies exposed to methadone during the same time frame. 

Greater birth weight with buprenorphine

Twelve percent of babies whose mothers took buprenorphine in early pregnancy were small for their gestational age, compared with 15.3% of those exposed to methadone. Finally, 8.3% of infants exposed to buprenorphine in early pregnancy had an abnormally low birth weight, versus 14.9% of those exposed to methadone.

The researchers found that exposure to buprenorphine versus methadone did not affect whether babies were delivered by Cesarean section, or if the mother experienced life-threatening medical conditions caused by or aggravated by the pregnancy. They also considered many potential confounding variables, including the mother’s mental health, any chronic coexisting conditions, other medication use, social issues such as homelessness and domestic violence, and individuals’ demographics. 

“We were able to generate precise estimates regarding the beneficial effects of buprenorphine,” Bateman said. “It’s a clear suggestion that these are causal effects and that they’re not confounded by patient characteristics that are different between the two groups.”

The hope is that the research will help providers select the proper treatment for pregnant women suffering from opioid addiction.  

“The choice of treatment for opioid use disorder really needs to be individualized,” Bateman said. “Some patients may benefit from buprenorphine, and some may benefit from methadone. But all things being equal, our data suggests that obstetrical outcomes are better in patients who are treated with buprenorphine during pregnancy compared with methadone.”

The research was funded by the National Institute on Drug Abuse (grant R01DA049822).

About Stanford Medicine

Stanford Medicine is an integrated academic health system comprising the Stanford School of Medicine and adult and pediatric health care delivery systems. Together, they harness the full potential of biomedicine through collaborative research, education and clinical care for patients. For more information, please visit

2024 ISSUE 1

Psychiatry’s new frontiers