Mickey Heinbaugh, B.S.
Drexel University College of Medicine
SUMMARY POINTS
The prevalence of Opioid Use Disorder in pregnancy has increased in the United States and is a consequence of the opioid epidemic.
The standard care for treating Opioid Use Disorder in pregnancy is methadone,
buprenorphine, or buprenorphine-naloxone.
There is evidence that using buprenorphine based medications to treat Opioid Use
Disorder in pregnancy may have better outcomes than methadone for the patient and child.
Although recent research suggests that buprenorphine medications may result in better outcomes, there are still areas of research to be investigated regarding the use of one medication over the other.
Background
The rise in Opioid Use Disorder (OUD) among pregnant individuals is thought to be due
in part to the increased prescribing of opioids which first started in the 1990’s (1). Between 1995 and 2009, the prescription of opioids in pregnant women nearly doubled (2). According to the Center for Disease Control, the number of pregnant women who suffered from OUD at the time of delivery more than quadrupled between 1999 and 2014 (3).
The ability of opioids to cross the placenta result in adverse health effects for the neonate. Some of these effects include growth restriction, preterm birth, stillbirth, and Neonatal Abstinence Syndrome (NAS) (4). The multitude of health concerns for fetuses exposed to opioids highlights the importance of having a safe and effective treatment for OUD in pregnant patients. As of today, the standard care for treating a pregnant person with OUD is prescribing methadone, buprenorphine, or buprenorphine- naloxone (5). These treatments are associated with improved adherence to prenatal
care, lower incidence of preterm delivery, and fewer incidents of overdose (1).
Recent research has shown that infants who were exposed to buprenorphine based medications to treat OUD during pregnancy have better health outcomes than those who were exposed to methadone treatment (6,7). The purpose of this research analysis is to discuss the results of studies on treatment outcomes when using buprenorphine based medications or methadone in treating Opioid Use Disorder.
Analysis
In 2022, Suarez et al. investigated the difference in treatment outcomes between
buprenorphine and methadone for opioid maintenance therapy during pregnancy (6). A large cohort of pregnant patients during the period from 2000-2018 (2,548,372 that ended in live births) were included within the study. The data was drawn from a large database of medicaid beneficiaries. The outcomes studied were the prevalence of Neonatal Abstinence Syndrome (NAS), size for gestational age, preterm birth, and low birth weight in neonates exposed to either methadone or buprenorphine during pregnancy. NAS occurred in 52% of the neonates who were exposed to buprenorphine compared to 69.2% of those exposed to methadone (Relative Risk = 0.73, 95% confidence interval = 0.71 to 0.75). Small size for gestational age was seen in 12.1% of neonates exposed to buprenorphine compared to 15.3% of those exposed to methadone (Relative risk = 0.72, 95% CI = 0.66 to 0.80). Preterm birth occurred in 14.4% of infants exposed to buprenorphine compared to 24.9% of those exposed to methadone (Relative Risk = 0.58, 95% CI= 0.53 to 0.62). Low birth weight was seen in 8.3% of infants exposed to buprenorphine compared to 14.9% of those exposed to methadone (Relative risk = 0.56, 95% CI = 0.50 to 0.63) (Table 1).
Table 1. Absolute risk of neonatal outcomes when comparing buprenorphine vs. methadone. See Link from Suarez EA, Huybrechts KF, Straub L, et al. See Link: Buprenorphine versus Methadone for Opioid Use Disorder in Pregnancy. N Engl J Med 2022; 387:2033-2044.
This study concluded that the use of buprenorphine to treat OUD during pregnancy was
associated with a lower risk of adverse outcomes when compared to methadone (6). There was an inverse association between buprenorphine use and the measured outcomes.
Another study that reinforced these results was conducted by Kanervo et al. Within the
study, prescribed buprenorphine-naloxone was found to be a potential means of treating opioid use disorder (7). The study utilized 67 mother-child dyads at Helsinki University Women’s Hospital were included in the study. The results of this study allowed for multiple conclusions to be drawn regarding the health outcomes of the neonate and mother. Overall, the daily dose of maintenance medication was able to be reduced in 62% of pregnant patients. These reductions were most commonly seen in the buprenorphine group (79%) and the buprenorphine-naloxone group (65%). The likelihood of reducing the dosage of medication was less common in the methadone group (40%). Kanervo et al. also found that it was significantly more common for
those in the methadone group to use illicit drugs (80%) than in the buprenorphine naloxone group (22%) and buprenorphine monotherapy group (20%) (7). The drugs that were considered in this study were benzodiazepines, cannabis, stimulants, and additional opioids (Table 2).
Table 2: Illicit drug use during pregnancy in groups that were treated with three different types of opioid maintenance therapy (See link : Kanervo et al. 2022)
The outcomes for neonates in this study supported the findings of Suarez et al. Neonates in the methadone group tended to be the smallest for gestational age, and it was noted that these neonates had a smaller head circumference than those in the buprenorphine-based groups. 19% of neonates in the buprenorphine-naloxone group and 20% in the buprenorphine monotherapy group were small for gestational age, while 33% in the methadone group received the same diagnosis (Table 3) (7).
Table 3. Weight, length, and head circumference using relative measures expressed as standard deviation of neonates born to mothers using various forms of opioid maintenance therapy. See Link: Kanervo MM, Tupola SJ, Nikkola EM, et al. Buprenorphine- naloxone, buprenorphine, and methadone throughout pregnancy in maternal opioid use disorder. Acta Obstet Gynecol Scand. 2023; 102: 313- 322.
This study also monitored the neonates for Neonatal Opioid Withdrawal Syndrome
(NOWS) symptoms. It was found that 87% of neonates in the methadone group needed
pharmacological treatment for NOWS after birth, while only 67% needed this treatment in the buprenorphine group and only 51% in the buprenorphine-naloxone group.
Overall, the recent studies conducted by Suarez et al. and Kanervo et al. both support the notion that buprenorphine based opioid maintenance therapy may result in better treatment outcomes than using methadone for pregnant patients with OUD.
Discussion
Currently, the standard of care for treating pregnant individuals with opioid use disorder
is prescription of methadone or buprenorphine based medications in combination with
counseling and behavioral therapy. However, recent research suggests that there may be advantages to using buprenorphine based medications over methadone. In addition to the increased risk of adverse health effects seen in these studies, methadone has significant pharmacokinetic interactions with many other medications. These interactions pose another disadvantage of using methadone over buprenorphine (8).
Despite many recent studies examining the use of buprenorphine based methods vs.
methadone for treatment of OUD in pregnancy, there are still many questions to be investigated and answered. For example, there is limited research and evidence that methadone may be associated with a greater risk of stillbirth than buprenorphine. This association would result in an underestimation of the protective effects of buprenorphine (6). It would also be worthwhile to investigate the effect that the dosage of buprenorphine or methadone has on neonatal and maternal outcomes during pregnancy and postpartum (6).
REFERENCES
1. ODonnell FT, Jackson DL. Opioid Use Disorder and Pregnancy. Missouri Medicine.
2017 May-Jun;114(3):181-186.
2. National Institute on Drug Abuse. What treatment is available for pregnant mothers and
their babies? 2021, April. https://nida.nih.gov/publications/research-reports/medications-
to-treat-opioid-addiction/what-treatment-available-pregnant-mothers-their-babies.
3. Haight SC, Ko JY, Tong VT, et al. Opioid Use Disorder Documented at Delivery
Hospitalization – United States 1999-2014. Morbidity and Mortality Weekly Report
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4. Anbalagan S, Mendez MD, Neonatal Abstinence Syndrome. StatPearls. Updated 2023
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6. Suarez EA, Huybrechts KF, Straub L, et al. Buprenorphine versus Methadone for Opioid
Use Disorder in Pregnancy. N Engl J Med 2022; 387:2033-2044.
7. Kanervo MM, Tupola SJ, Nikkola EM, et al. Buprenorphine-naloxone, buprenorphine,
and methadone throughout pregnancy in maternal opioid use disorder. Acta Obstet
Gynecol Scand. 2023; 102: 313- 322.
8. The American College of Obstetricians and Gynecologists. Opioid Use and Opioid Use
Disorder in Pregnancy. Updated 2021. https://www.acog.org/clinical/clinical-
guidance/committee-opinion/articles/2017/08/opioid-use-and-opioid-use-disorder-in-
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