Children born to mothers who used buprenorphine for opioid addiction during pregnancy do not have a greater risk of neurodevelopmental disorders, such as ADHD and autism, compared with children whose mothers took methadone, finds a large US study published by The BMJ today.
The researchers say these findings “further support buprenorphine as a safe treatment option for opioid use disorder during pregnancy.”
Buprenorphine and methadone are recommended for the treatment of opioid use disorder during pregnancy. Previous research has shown that buprenorphine is associated with a lower risk of serious health complications for newborns compared with methadone, but evidence on long term safety is lacking.
To address this gap, researchers used Medicaid health insurance data for over 2.5 million live births from 2000 to 2018 to compare the risk of neurodevelopmental disorders in 12,635 children exposed to buprenorphine with 5,390 children exposed to methadone before birth (prenatally).
The children were tracked up to age 8 for conditions including autism, ADHD, speech or language disorder, behavioural disorder, and intellectual disability.
The researchers accounted for a range of potentially influential factors including mother’s age, ethnicity, tobacco and alcohol use, chronic pain, mental health conditions, and use of other medications and healthcare.
After adjusting for these variables, children with prenatal exposure to buprenorphine had a slightly lower (19%) risk of any neurodevelopmental disorder by age 8 compared with those exposed to methadone.
Prenatal exposure to buprenorphine was also associated with a lower risk of specific neurodevelopmental disorders compared with methadone including ADHD (11% lower risk), speech or language disorder (16% lower risk), and autism (26% lower risk).
For women who were already using buprenorphine or methadone before pregnancy (prevalent use), prenatal exposure to buprenorphine was linked to a 38% lower risk of any neurodevelopmental disorder compared with methadone exposure.
However, this association was not observed among women who initiated treatment during pregnancy (new use), a finding the authors suggest requires further study.
Additional analyses to further account for bias also suggested that prenatal buprenorphine exposure does not increase the risk of long term adverse neurodevelopmental outcomes compared with methadone.
This is an observational study, so no firm conclusions can be drawn about cause and effect and the researchers acknowledge some limitations. But they say their use of a large representative health insurance database and extensive sensitivity analyses to examine different sources of bias suggest the findings are robust.
As such, they conclude: “The findings of this study suggest no increased risk of long term adverse neurodevelopmental outcomes among children with prenatal exposure to buprenorphine versus methadone, further supporting buprenorphine as a safe treatment option for opioid use disorder during pregnancy.”
These findings are reassuring and should increase confidence in buprenorphine as an option during pregnancy, say Australian researchers in a linked editorial.
However, they stress methadone’s importance for those with higher opioid tolerance or more complex needs and the need to address stigma, fragmented services, and structural inequities that hinder care for people with opioid use disorder.
Further research is also needed on other outcomes and new formulations, such as long-acting injectable buprenorphine (currently unstudied in pregnancy) and to ensure that clinical recommendations remain evidence-based and responsive to evolving medication options for opioid use disorder, they conclude.
The BMJ
Observational study
People
Prenatal exposure to buprenorphine or methadone and adverse neurodevelopmental outcomes: population based cohort study
15-Apr-2026
All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: this work was supported by the National Institute on Drug Abuse/ National Institutes of Health; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. KFH reported being an investigator on grants to Brigham and Women’s Hospital from UCB, Takeda, and GSK outside the submitted work; LS reported receiving grants to Brigham and Women’s Hospital from GSK outside the submitted work; SH-D reported receiving personal fees from Roche, Vertex, and Biogen and grants to her institution from Takeda Pharmaceuticals, GSK, and UCB outside the submitted work; and YZ reports being an investigator on a research grant from Takeda and GSK to her institution for an unrelated study