Evidence map›Paper›PMID 41985931›Full record

ArticleBMJ (Clinical research ed.)2026

Prenatal exposure to buprenorphine or methadone and adverse neurodevelopmental outcomes: population based cohort study.

Sabine Friedrich, Krista F Huybrechts, Loreen Straub, Sonia Hernandez-Diaz, Yanmin Zhu, Georg Hahn, Helen Mogun, Hendrée E Jones, Hilary S Connery, Jonathan M Davis and 4 more

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In one paragraph

Article in BMJ (Clinical research ed.), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Sabine FriedrichDivision of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02120, USA h4p@bwh.harvard.edu.ORCID https://orcid.org/0000-0002-2272-6318
Krista F HuybrechtsDivision of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02120, USA.
Loreen StraubDivision of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02120, USA.
Sonia Hernandez-DiazDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
Yanmin ZhuDivision of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02120, USA.
Georg HahnDivision of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02120, USA.
Helen MogunDivision of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02120, USA.
Hendrée E JonesUNC Horizons and Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Hilary S ConneryDivision of Alcohol, Drugs, and Addiction, McLean Hospital and Department of Psychiatry, Harvard Medical School, Belmont, MA, USA.
Jonathan M DavisDepartment of Pediatrics, Tufts Medical Center and the Tufts Clinical and Translational Science Institute, Boston, MA, USA.
Kathryn J GrayDepartment of Obstetrics and Gynecology, University of Washington, Seattle, WA, USA.
Barry LesterCenter for the Study of Children at Risk, Departments of Psychiatry and Pediatrics, Alpert Medical School of Brown University, and Women and Infants Hospital, Providence, RI, USA.
Mishka TerplanFriends Research Institute, Baltimore, MD, USA.
Brian T BatemanDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveTo compare the incidence of neurodevelopmental disorders among children with prenatal exposure to buprenorphine versus methadone.

designPopulation based cohort study.

settingUS nationwide Medicaid data on >2.5 million live births from 2000 to 2018.

participants18 612 pregnancies exposed to buprenorphine or methadone, of which 587 were excluded from the analysis owing to exposure to the comparator drug.

main outcome measuresThe primary outcome was a composite of neurodevelopmental disorders (autism spectrum disorder, attention deficit/hyperactivity disorder, developmental speech or language disorder, developmental coordination disorder, behavioural disorder, learning difficulty, or intellectual disability). Individual neurodevelopmental disorders were considered secondary outcomes. Cumulative incidences were obtained using Kaplan-Meier analyses, and hazard ratios using Cox proportional hazards regression. Propensity score overlap weighting was applied to adjust for confounding, including personal characteristics, maternal medical and mental health comorbidities, exposure to medications and other substances, proxies for severity of opioid use disorder, healthcare utilisation, and adequacy of prenatal care utilisation.

results12 635 children were exposed to buprenorphine and 5390 to methadone prenatally. The crude cumulative incidence of any neurodevelopmental disorder at age 8 years among those exposed to buprenorphine was 34% (95% confidence interval (CI) 30% to 38%) and among those exposed to methadone was 33% (29% to 37%). Adjusted analyses suggested slightly lower hazards of any neurodevelopmental disorder associated with exposure to buprenorphine versus methadone (adjusted hazard ratio 0.81, 95% CI 0.70 to 0.94). Similar results were obtained for the individual neurodevelopmental disorders such as attention deficit/hyperactivity disorder (0.89, 0.65 to 1.21) and autism spectrum disorder (0.74, 0.46 to 1.21). With prevalent use, prenatal exposure to buprenorphine was associated with lower hazards of any neurodevelopmental disorder compared with prenatal exposure to methadone (adjusted hazard ratio 0.62, 0.51 to 0.76). This association was not observed with treatment initiation during pregnancy (adjusted hazard ratio 1.13, 0.90 to 1.42). Further sensitivity analyses indicated results consistent with no increased risk of neurodevelopmental disorders among pregnancies exposed to buprenorphine versus methadone.

conclusionsThe 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.

Indexed as

BuprenorphineMethadoneNeurodevelopmental DisordersOpioid-Related DisordersPrenatal Exposure Delayed EffectsAdultAnalgesics, OpioidChildChild, PreschoolCohort StudiesFemaleHumansIncidenceMaleOpiate Substitution TreatmentPregnancyAnalgesics, OpioidBuprenorphineMethadone

Identifiers

PMID41985931
PMCPMC13081224

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.