Neurodevelopmental outcomes in children prenatally exposed to opioid maintenance treatment: A population-based study

Opioid maintenance treatment (OMT), with methadone or buprenorphine, is a key approach for managing opioid use disorder (OUD) during pregnancy. Despite buprenorphine's superior short-term outcomes, its long-term effects remain understudied. This study aims to evaluate the effects of prenatal OMT exposure on the incidence of childhood neurodevelopmental disorders (NDDs) considering timing effect.

A retrospective cohort study using Rhode Island Medicaid data linked to vital statistics from 2008 to 2018 was conducted. The study included pregnancies having live birth from 2008 to 2016 with continuous Medicaid insurance and OUD diagnosis within 3 months preceding conception until delivery. At least one buprenorphine dispensing or a claim of methadone was required for exposure definition. Exposure was evaluated during early (0-90 days) or late (>90 days) gestation, or at any pregnancy phase. NDDs, including autism, attention-deficit/hyperactivity disorder (ADHD), learning disabilities, speech/language disorders, developmental coordination disorder, intellectual disability, and behavioral disorders, were identified using validated algorithms. Applying Cox proportional-hazard models with propensity score overlap weighting, adjusted hazard ratios (aHR) were calculated, mitigating potential confounders. Children were followed up from birth until NDD diagnosis, disenrollment, or study end.

Of 416 mother-child dyads with OUD, 40% used methadone and 20% had buprenorphine exposure during pregnancy. NDDs were observed in 36% of children with early methadone exposure compared to 17% in the early buprenorphine exposed group (aHR: 2.75; 95% confidence interval [CI]: 1.42-5.35). Further comparison to late buprenorphine exposure, late methadone exposure was associated with higher NDD risk (aHR: 2.05; 95% CI: 1.09-3.86). Compared to unexposed group, children exposed to methadone during early and late periods showed higher NDD incidences (aHR: 2.33; 95% CI: 1.51-3.60 and aHR: 2.42; 95% CI: 1.54-3.80, respectively).

The study suggests that buprenorphine is a good treatment option for OUD during pregnancy due to minimal long-term neurodevelopmental impacts on children. However, further extensive research is necessary to rule-out potential confounding.