Comment on “Prenatal Exposure to Buprenorphine or Methadone and Adverse Neurodevelopmental Outcomes: Population-Based Cohort Study”

Abstract

Medications for opioid use disorder (MOUD), specifically buprenorphine and methadone, are the recommended treatments during pregnancy because they improve maternal outcomes and reduce adverse neonatal events. Methadone is a full mu-opioid receptor agonist that typically requires daily clinic visits, whereas buprenorphine is a partial mu-opioid receptor agonist and kappa receptor antagonist that can be prescribed and dispensed in outpatient settings. Although recent studies have suggested better short-term neonatal outcomes with buprenorphine, evidence comparing these MOUD on long-term neurodevelopmental safety has been mixed. The aim of this study was to compare the prenatal use of buprenorphine and methadone on childhood neurodevelopmental disorders. This was a population-based cohort study, analyzing Medicaid data between January 1, 2000, and December 31, 2018. Included were pregnant individuals aged 12 to 55 and their children. Children were followed for up to 8 years. Excluded were pregnancies with chromosomal abnormality or exposure to buprenorphine, methadone, or comparator drug in the 3 months before the start of pregnancy. The exposures included buprenorphine (defined as buprenorphine alone or with naloxone) and methadone. The primary outcome was a composite of neurodevelopmental disorders, including autism spectrum disorder, attention-deficit/hyperactivity disorder (ADHD), developmental speech or language disorder, developmental coordination disorder, behavioral disorders, learning difficulties, and intellectual disability. A total of 18,025 pregnancies were included in the analysis, with 12,635 exposed to buprenorphine and 5390 exposed to methadone. The crude cumulative incidence of any neurodevelopmental disorder by age 8 was similar between buprenorphine (33.9%; 95% CI, 29.8%-37.8%) and methadone (33.1%; 95% CI, 28.8%-37.1%). After adjustment, exposure to buprenorphine was associated with a slightly lower hazard of any neurodevelopmental disorder compared with methadone [adjusted hazard ratio (aHR), 0.81; 95% CI, 0.70-0.94]. The 2 most common neurodevelopmental disorders were ADHD (aHR, 0.89; 95% CI, 0.65-1.21) and autism spectrum disorder (aHR, 0.74; 95% CI, 0.46-1.21). Similar findings were obtained in multiple sensitivity and subgroup analyses for individual neurodevelopmental disorders. In conclusion, prenatal exposure to buprenorphine was not associated with an increased risk of long-term neurodevelopmental disorders compared with methadone. (Summarized from 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).