Buprenorphine and Methadone in Pregnancy: What the Latest Data Show About Child Development

New Data on Prenatal MOUD Exposure

Emerging data published in The BMJ revealed that prenatal exposure to buprenorphine is not associated with an increased risk of long-term neurodevelopmental disorders such as autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), developmental speech or language disorders, and learning disabilities in comparison with methadone.¹

Among more than 18,000 pregnancies, the development of ASD and ADHD occurred at similar rates between the 2 treatment groups in the research that consisted of pregnancies with prenatal exposure to buprenorphine and pregnancies with prenatal exposure to methadone.¹ The implications of these data support the safety of using buprenorphine for opioid use disorder (OUD) during pregnancy.¹

OUD Treatment in Pregnancy

OUD is a continuously pressing public health concern, particularly among individuals undergoing pregnancy. When OUD goes untreated, there is an increased risk of maternal overdose, preterm birth, and poor neonatal outcomes such as low birth weight, neonatal opioid withdrawal syndrome, respiratory complications at birth, and fetal growth restriction.² 

The recommended standard therapy for OUD during pregnancy is the use of medications for opioid use disorder (MOUD) such as buprenorphine and methadone.² Methadone is a full μ-opioid receptor agonist (MOR) that behaves as the primary target for opioid analgesics and is typically administered through regulated clinics, which require daily visits. Buprenorphine is a partial MOR agonist and κ-opioid kappa antagonist that could be prescribed in outpatient circumstances.² These 2 MOUD treatments differ in their effects on the body and their accessibility, which influence treatment adherence, accessibility, and any potential maternal and neonatal outcomes.

Previous data suggest an improvement in neonatal outcomes with buprenorphine use that includes reduced severity of neonatal opioid withdrawal syndrome.³^,⁴ However, current data on long-term neurodevelopmental outcomes in exposed children are limited due to small sample sizes and short follow-up durations.¹

Research Design and Methods

Researchers conducted a study using Medicaid data from 2000 to 2018, including over 2.5 million live births.¹ The analysis focused on 18,025 pregnancies exposed to either buprenorphine (n = 12,635) or methadone (n = 5390).¹

The primary outcome was a composite measure of neurodevelopmental disorders, including ASD, ADHD, speech and language disorders, learning disabilities, and intellectual disability.¹ This composite end point was used to capture a broad range of developmental outcomes in exposed children. Children were followed for up to 8 years after birth to assess the development of neurodevelopmental disorders.¹

To reduce confounding factors, researchers used propensity score overlap weighting and Cox proportional hazards models.¹ Analyses were adjusted for maternal demographics, comorbidities, substance use, and health care utilization to better balance the comparison groups.¹

Key Findings

At 8 years of follow-up, the crude cumulative incidence of neurodevelopmental disorders was similar between groups¹:

• 34% for buprenorphine exposure
• 33% for methadone exposure

After adjustment, buprenorphine exposure was associated with a modestly lower risk of neurodevelopmental disorders compared with methadone (adjusted HR [aHR], 0.81; 95% CI, 0.70-0.94).¹

Individual outcomes, including ADHD and ASD, also showed no increased risk with buprenorphine.¹ Sensitivity and subgroup analyses consistently supported these findings.¹ Notably, among patients with established (prepregnancy) treatment, buprenorphine was associated with a lower risk (aHR, 0.62; 95% CI, 0.51-0.76), whereas no difference was observed in those initiating treatment during pregnancy.¹

These results indicate comparable long-term neurodevelopmental safety between the 2 therapies, with no evidence of increased risk associated with buprenorphine.¹

Pharmacist Implications

This is particularly relevant for clinicians involved with the management of OUD during pregnancy. With buprenorphine’s comparable safety profile, combined with its outpatient prescribing flexibility, this may improve access to treatment and adherence.²

It is essential to continue support for patients who use MOUD during pregnancy through medication safety counseling, treatment adherence, and expectations for maternal and neonatal outcomes.² Pharmacists should acknowledge that this population remains at elevated baseline risk for neurodevelopmental disorders and emphasize the severity of early pediatric monitoring and intervention.¹

Although pharmacists collaborate with the prescribers of MOUD, they can assist in guiding individualized therapy selection through patient access, treatment history, and acknowledging the risk of relapse.²^,⁵ These data reinforce the importance of maintaining continuity of care for patients already stabilized on MOUD prior to pregnancy.¹ These results support existing guidelines recommending buprenorphine as a safe and effective treatment option for OUD during pregnancy and provide reassurance to clinicians and patients making treatment decisions.²^,⁵

REFERENCES

1. Friedrich S, Huybrechts KF, Straub L, et al. Prenatal exposure to buprenorphine or methadone and adverse neurodevelopmental outcomes: population-based cohort study. BMJ. 2026:393:e087321. doi:10.1136/bmj-2025-087321

2. Sanjanwala AR, Lim G, Krans EE. Opioid and opioid use disorder in pregnancy. Obstet Gynecol Clin North Am. 2023;50(1):229-240. doi:10.1016/j.ogc.2022.10.015

3. Zedler BK, Mann AL, Kim MM, et al. Buprenorphine compared with methadone to treat pregnant women with opioid use disorder: a systematic review and meta-analysis of safety in the mother, fetus, and child. Addiction. 2016;111(12):2115-2128. doi:10.1111/add.13462

4. Minozzi S, Amato L, Jahanfar S, Bellisario C, Ferri M, Davoli M. Maintenance agonist treatments for opiate-dependent pregnant women. Cochrane Database Syst Rev. 2020;11(11):CD006318. doi:10.1002/14651858.CD006318.pub4

5. Substance Abuse and Mental Health Services Administration (SAMHSA). Medications for opioid use disorder treatment improvement protocol (TIP 63). 2021. Accessed April 20, 2026. https://library.samhsa.gov/product/tip-63-medications-opioid-use-disorder/pep21-02-01-002