Ph.D. student - Clinical Psychology Indiana University-Bloomington, United States
Background: Few studies have examined associations between prenatal exposure to prescribed opioid analgesics (POAs) and offspring neurodevelopmental disorders. Existing research suggests risk increases with amount of exposure during pregnancy, but limitations, like inadequate confounding control, preclude strong inferences regarding the degree to which POAs cause these conditions.
Objectives: To evaluate the associations between exposure to POAs during pregnancy and risk for autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) in offspring, independent of measured covariates.
Methods: This retrospective cohort study included a population-based sample of 473,417 offspring, born 2007-2011 and followed up through 2013. Swedish national registers included information on 96-99% of births, as well as maternal, paternal, and socioeconomic characteristics. Key exclusion criteria included multiple births, stillbirths, maternal opioid use disorder diagnosis and use of methadone or buprenorphine. The exposure was maternal POA dispensations (Anatomical Therapeutic Chemical codes starting with N02A, N02BE51) during pregnancy, defined as any exposure and 1, 2, or ≥3 prescriptions. The offspring outcomes, ASD and ADHD, were identified by clinical diagnoses (ICD-10 codes F84, F90) and dispensed ADHD medications. Inverse probability of treatment weighting accounted for covariates in Cox proportional hazards regression. Multiple imputation was used to address missing (≤4%) on covariates.
Results: The cumulative incidence of diagnosis by age 5 was higher among exposed offspring for ASD [Kaplan-Meier estimate (KM)=0.75%] and for ADHD (KM=0.47%) compared to unexposed offspring (ASD KM=0.45%; ADHD KM=0.14%). 4.38% of births were exposed to POAs at any point during pregnancy. After covariate adjustment, receiving more POA prescriptions was associated with greater risk of ASD [Hazard Ratio (HR; # prescriptions), 95% Confidence Interval (CI); HR(1) 1.40, 95% CI: 1.1-1.8; HR(2) 3.07, 95% CI: 2.1-4.5; HR(≥3) 1.44, 95% CI: 0.8-2.6] and ADHD [HR(1) 1.89, 95% CI: 1.4-2.6; HR(2) 3.91, 95% CI: 2.3-6.5; HR(≥3) 4.76, 95% CI: 2.9-7.7].
Conclusions: These preliminary analyses support previous findings that risk of offspring neurodevelopmental disorders increases as amount of exposure to POAs increases. Results will be updated ahead of presentation with data through 2021. The larger sample will increase precision when estimating risks. Updated analyses will include a sibling comparison to account for confounding by genetic and environmental factors. This work has important clinical implications, as it will help to define the risks associated with POA exposure during pregnancy in relation to offspring neurodevelopmental disorders.
