Background: Opioid maintenance treatment (OMT) with methadone or buprenorphine during pregnancy is recommended to prevent complications of opioid abuse, addiction and withdrawal, and encourage prenatal care and drug treatment. However, data evaluating long-term effects of OMT on neurodevelopmental outcomes in children remains sparse.
Objectives: To compare risk of childhood neurodevelopmental disorders (NDDs) among children exposed to buprenorphine or methadone OMT during pregnancy.
Methods: A retrospective cohort study using RI Medicaid data linked with vital statistics assessed pregnant women with opioid use disorder (OUD) who had a live birth from 2008 to 2016. Exposure to OMT was assessed in three gestational intervals: early exposure (0-90 days), late exposure (>90 days), or exposure during any gestational time period. Primary outcome was defined as the occurrence of any of the following NDDs: autism spectrum disorder/pervasive developmental disorder, attention deficit disorder or other hyperkinetic syndromes of childhood, developmental speech or language disorder, developmental coordination disorder, intellectual disability, and behavioral disorder(s). Secondary analyses evaluated each incidence of NDD separately. Children were followed up from birth up to 11 years of age to assess incidence of NDDs. Cox proportional-hazard models were fitted to estimate hazard ratios, incorporating propensity score overlapping weights to adjust for potential confounders. Mediation analyses were performed to identify potential mediators for the OMT–NDD pathway. Sensitivity analyses included inverse probability of censoring weighting and dose responses for buprenorphine.
Results: Of 416 mother-child dyads who had OUD, 40% were exposed to methadone and 20% were exposed to buprenorphine during the pregnancy period. NDDs developed in 36% of those children exposed early to methadone compared to 20% of those exposed to buprenorphine (aHR: 2.65; 95%CI: 1.34-5.23), for which low birth weight mediated 11% of the total effect. Late methadone exposure was associated with a higher NDD risk compared to buprenorphine (aHR: 2.07; 95%CI: 1.08-3.95). Compared to the unexposed cohort, children exposed to methadone during early and later trimesters had a higher NDD incidence (aHR: 2.33; 95%CI: 1.51-3.60, aHR: 2.47; 95%CI: 1.57-3.87, respectively).
Conclusions: Buprenorphine was associated with improved long-term childhood outcomes compared to methadone. Further research examining the safety differences of prenatal exposure to both agents and long-term neurodevelopmental outcomes in children is warranted.
