Children with prenatal exposure to buprenorphine do not appear to have an elevated risk of long-term adverse neurodevelopmental outcomes relative to those exposed to methadone, suggests a study.
“Compared with methadone, buprenorphine treatment during pregnancy (alone or combined with naloxone) for opioid use disorder was not associated with an increased risk of any neurodevelopmental disorder,” the investigators said.
A total of 18,612 pregnancies exposed to either buprenorphine or methadone were included in this population-based cohort study. Of these, 587 were excluded from the analysis due to exposure to the comparator drug.
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) served as the primary outcome. Secondary outcomes included individual neurodevelopment disorders.
The investigators obtained the cumulative incidences using Kaplan–Meier analyses and calculated the hazard ratios (HRs) using Cox proportional hazards regression. They applied propensity score overlap weighting to adjust for confounders.
Lower hazards
Overall, 12,635 children had been exposed to buprenorphine and 5,390 to methadone prenatally. [BMJ 2026;393:e087321]
At age 8 years, the crude cumulative incidence of any neurodevelopmental disorder was 34 percent (95 percent confidence interval [CI], 30–38) among children exposed to buprenorphine and 33 percent (95 percent CI, 29–37) among those exposed to methadone.
In adjusted analyses, exposure to buprenorphine vs methadone correlated with a reduced risk of any neurodevelopmental disorder (adjusted [a]HR, 0.81, 95 percent confidence interval [CI], 0.70–0.94).
These results persisted for the individual neurodevelopmental disorders, such as attention deficit/hyperactivity disorder (aHR, 0.89, 95 percent CI, 0.65–1.21) and autism spectrum disorder (aHR, 0.74, 95 percent CI, 0.46–1.21).
With prevalent use, prenatal exposure to buprenorphine vs methadone resulted in a lower risk of any neurodevelopmental disorder (aHR, 0.62, 95 percent CI, 0.51–0.76). However, this finding was not seen with treatment initiation during pregnancy (aHR, 1.13, 95 percent CI, 0.90–1.42).
“Further sensitivity analyses indicated results consistent with no increased risk of neurodevelopmental disorders among pregnancies exposed to buprenorphine versus methadone,” the investigators said.
“The findings of this study suggest no increased risk of long-term adverse neurodevelopmental outcomes among children with prenatal exposure to buprenorphine vs methadone, further supporting buprenorphine as a safe treatment option for opioid use disorder during pregnancy,” they added.
Previous studies
Studies directly comparing neurodevelopmental outcomes among children with prenatal exposure to buprenorphine vs methadone are scarce.
Results of these studies suggest either superior neurodevelopmental outcome following prenatal exposure to buprenorphine or a similar risk between the two drugs. [Addiction 2012;107(Suppl 1):63-73; Pharmacotherapy 2024;44:770-781; Neurotoxicol Teratol 2010;32:280-288; J Addict Res Ther 2016;doi:10.4172/2155-6105.1000263; J Perinatol 2015;35:656-659]
However, the available evidence is limited to the assessment of early neurodevelopmental outcomes, small sample sizes, and poor control of potential confounders. [Drug Alcohol Depend 2018;185:40-49; Eur Addict Res 2015;21:63-70]
“Treatment with opioid agonists during pregnancy is crucial to improve outcomes for both pregnant individuals and their children,” the investigators said.
The conclusion of the current study "coupled with previous findings of a lower risk of adverse neonatal outcomes should provide reassurance for providers and individuals considering treatment with buprenorphine during pregnancy,” they added.