Prenatal Prescription Opioid Analgesic Exposure and Academic Performance in Third Grade Children: A Population-Based...

To evaluate the association between prenatal exposure to opioids analgesics and academic performance in third grade children.

Population-based cohort study using linked data from New South Wales birth records, medicine dispensing data, and national standardised test results.

New South Wales, Australia (2003-2011).

Liveborn children of concessional women, excluding those whose mothers lived interstate, were overseas visitors, or had records of opioid dependence.

Exposure was defined as ≥ 1 opioid dispensed during pregnancy stratified by pregnancy timing, dose, and type of monotherapy. Reading and numeracy z-scores were compared between children with and without prenatal opioid exposure using linear mixed-effects models incorporating propensity score weights and accounting for maternal and school clustering.

Standardised national reading and numeracy Z-scores for third-grade children.

Among 85,478 eligible children, 70,882 (82.9%) had test scores, with 7,664 (10.2%) prenatally exposed to opioids analgesics, mainly codeine. Prenatal e.xposure to opioid analgesics was associated with a slight decrease in standardised reading and numeracy test scores (adjusted mean difference [aβ] -0.05, 95% CI -0.06 to -0.03), below the conventional threshold for a small effect (Cohen's d = 0.2). Codeine and oxycodone results were similar to those for any opioid exposure, while a larger difference was observed for tramadol (reading aβ -0.25, 95% CI -0.31 to -0.18; numeracy aβ -0.22, 95% CI -0.29 to -0.16).

Prenatal exposure to codeine and oxycodone do not have meaningful impacts on third-grade academic performance. In contrast, tramadol was associated with lower reading and numeracy scores, though whether this reflects a true effect or is attributable to unmeasured confounding remains unclear and warrants further investigation.