Does opioid replacement therapy for infants with prenatal opioid exposure modify the risk of ADHD in childhood? A matched cohort analysis.

IMPORTANCE

Prenatal opioid exposure (POE) in infants has been associated with increased risk for attention-deficit/hyperactivity disorder (ADHD). Does opioid replacement therapy (ORT) in infants after delivery amplify adverse impact of POE? If so, this should inform clinical decision-making about ORT.

OBJECTIVE

Assess how ORT modifies effects of POE on ADHD risk.

DESIGN

Matched cohort study in a birth cohort (2010-2019). Each POE child is matched to 5 unexposed controls, balancing covariates within ORT and non-ORT POE subgroups.

SETTING

A large integrated Northern California health system.

PARTICIPANTS

Child/mother dyads with children born at 35 weeks or later without congenital anomalies.

EXPOSURE(S): POE was determined by dispensed opioid prescriptions from pharmacy records, urine drug screens, and chart review. ORT was determined using electronic administration records.

MAIN OUTCOME(S) AND MEASURE(S): ADHD, defined as the combination of an ICD-9/ICD-10 diagnosis code and two dispenses of ADHD medication.

RESULTS

Overall ADHD incidence was 1.0% (median event age 7 years, median follow-up time 5.9 years). 280 matched sets comparing infants with ORT to matched controls (without POE) exhibited a 0.1% risk difference for ADHD. 2986 matched sets comparing infants with POE but not ORT to matched controls exhibited a 0.7% risk difference. The difference between these effects was not significant (95% confidence interval: -1.9%,0.8%).

CONCLUSIONS AND RELEVANCE: Our analysis reveals no evidence that ORT modifies detrimental impacts of POE on ADHD susceptibility, although short follow-up times limited outcome ascertainment. These findings suggested cautious optimism in response to concerns about whether ORT may exacerbate effects of POE.