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

OBJECTIVE: To compare the incidence of neurodevelopmental disorders among children with prenatal exposure to buprenorphine versus methadone. DESIGN: Population based cohort study. SETTING: US nationwide Medicaid data on >2.5 million live births from 2000 to 2018. PARTICIPANTS: 18 612 pregnancies exposed to buprenorphine or methadone, of which 587 were excluded from the analysis owing to exposure to the comparator drug. MAIN OUTCOME MEASURES: The 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. RESULTS: 12 635 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. CONCLUSIONS: 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.