麻豆传媒

Buprenorphine treatment for pregnant patients with opioid use disorder (OUD) was linked with fewer neonatal risks compared with methadone therapy, but had similar maternal outcomes, an analysis of Medicaid data found.

Neonatal abstinence syndrome (NAS) occurred in 52% of infants whose mothers took buprenorphine in the 30 days before delivery compared with 69% of those whose mothers took methadone (adjusted relative risk 0.73, 95% CI 0.71-0.75), reported Elizabeth Suarez, PhD, MPH, of Brigham and Women's Hospital and Harvard Medical School, both in Boston, and colleagues.

Buprenorphine use in early pregnancy also was associated with lower rates of preterm birth, small size for gestational age, and low birthweight versus methadone use, they stated in the .

Patients exposed to either buprenorphine or methadone had similar C-section rates (33.6% vs 33.1%, respectively), as well as rates of severe maternal complications (3.3% vs 3.5%, respectively), the researchers found.

"Using buprenorphine to treat opioid use disorder in pregnancy may result in better outcomes for the infant than methadone," Suarez told 麻豆传媒 in an email.

"Methadone used to be the primary treatment for opioid use disorder in pregnancy, but now buprenorphine is more commonly used," she added. "Our results support buprenorphine as a first-line treatment in this population."

Suarez emphasized, however, that any treatment for opioid use disorder in pregnancy is better than no treatment. "While our results suggest better outcomes with buprenorphine, methadone is still a recommended treatment in pregnancy," she said.

Suarez, who is now at Rutgers Institute for Health, Health Policy and Aging Research in New Brunswick, New Jersey, noted that the findings confirm results of the 2010 Maternal Opioid Treatment: Human Experimental Research () trial. That trial found that infants exposed to in utero buprenorphine received less morphine to treat NAS, were hospitalized for less time, and had fewer symptoms of NAS than babies exposed to methadone, but had several limitations.

Suarez's group confirmed the lower risks associated with buprenorphine in a large sample size with a much narrower confidence interval, noted Elizabeth Krans, MD, of the University of Pittsburgh, in an . Still, there is a need for shared decision-making when treating pregnant patients with OUD, taking into account patient preferences, previous treatment, and medication availability, she wrote.

Krans also noted that "the use of buprenorphine has become more challenging with the escalation of the use of synthetic opioids such as fentanyl." Buprenorphine is a partial opioid receptor agonist and may not completely mitigate opioid cravings and could cause withdrawal in patients who use fentanyl -- a substance 50 to 100 times more potent than morphine, she added.

Further research "is desperately needed to expand treatment options for pregnant persons with opioid use disorder, especially while the opioid crisis continues to unfold," she stated.

Suarez and colleagues used nationwide Medicaid data to identify pregnancies from 2000 through 2018. They evaluated maternal and neonatal outcomes among patients who received buprenorphine monotherapy or buprenorphine-naloxone combination therapy versus methadone. NAS was assessed in relation to treatment administered in the 30 days leading up to delivery. Maternal outcomes included C-section rate and severe maternal complications.

The researchers adjusted for covariates including history of OUD, non-opioid substance use disorder, mental health or chronic conditions, medication use, demographics, and socioeconomic status.

The study included 2.5 million pregnancies that resulted in a live birth. In early pregnancy, 10,704 patients were exposed to buprenorphine and 4,387 to methadone; in late pregnancy, 11,272 and 5,056 were exposed, respectively. The majority of pregnant patients who were exposed to medication-assisted treatment in late pregnancy received treatment within 30 days of delivery.

Pregnant patients who took buprenorphine were more likely to be white, from the Northeast or Midwest, and to reside in rural areas than who received methadone. They also were more likely to receive diagnoses of depression or anxiety, have non-opioid substance use disorders, and use antidepressants. Those in the methadone cohort were more likely to use prescription opioids.

Babies exposed to buprenorphine in early pregnancy had lower rates of preterm birth (14.4% vs 24.9% exposed to methadone), small size for gestational age (12.1% vs 15.3%, respectively), and low birthweight (8.3% vs 14.9%). Lower risks were maintained for exposures in both early and late-stage pregnancies.

Suarez and colleagues noted that outcomes defined by healthcare utilization data may have been subject to misclassification, which was a study limitation. Residual confounding was possible because the researchers did not have information about lifestyle or behavioral factors. They also were unable to compare dose amounts or adjustment of doses for both medications, because the data did not include dosing information for patients treated with methadone.

Suarez said that "there is still a lack of robust data on the safety of buprenorphine and methadone for other birth outcomes, including birth defects." Future studies also should investigate differences in treatment retention with buprenorphine compared to methadone, she added.

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