1. Any exposure to opioid analgesics prenatally was not associated with differences in scholastic performance at the fifth-grade level, compared to those whose mothers had prepregnancy exposure only.
2. Prenatal exposure was associated with small decreases in test scores, for exposures in the first trimester and exposures in 2-3 four-week periods during pregnancy, compared to those whose mothers had prepregnancy exposure only.
Evidence Rating Level: 2 (Good)
While an estimated 3 to 22% of pregnant individuals use prescribed opioid analgesics, there is a lack of understanding about the neurodevelopmental implications of prenatal exposure. One prior study found that high cumulative exposures or exposures longer than 14 days increased the risk for neurodevelopmental disorders, with hazard ratios ranging from 1.22-1.70. The remaining three studies examining prenatal exposure to opioid analgesics found no associations with impaired language or communication skills, although an exposure of 5 weeks or longer was associated with a greater risk of ADHD diagnosis (HR 1.60). Therefore, this current cohort study examined whether any prenatal exposure, exposure timing, or exposure duration were associated with differences in scholastic skills at the fifth-grade level. The study population consisted of 64,256 children from 54,568 mothers, enrolled in a national birth registry between 2002 and 2008. The outcomes were scores from national standardized tests for mathematics, Norwegian literacy, and English language. The study found that 2.3% of pregnancies involved opioid analgesic use, and codeine with acetaminophen was the most common, reported by 90.5% of those with exposures. Of the students who were exempted from test-taking due to special needs, between 2.7% and 3.6% had exposures to opioid analgesics. Overall, children with any exposure did not score lower on any test, compared to children from mothers with only prepregnancy exposures. In terms of exposure timing, exposure in the first trimester was associated with lower literacy (weighted β -0.13, 95% CI -0.25 to -0.01) and lower numeracy (wβ -0.14, 95% CI -0.25 to -0.04) scores, compared to those from mothers with prepregnancy exposures only. Lastly, children of mothers who used opioid analgesics during 2-3 four-week periods in pregnancy had lower literacy (wβ -0.13, 95% CI -0.25 to -0.01) and lower numeracy (wβ -0.14, 95% CI -0.25 to -0.04) scores, compared to those from mothers with prepregnancy exposures only. No significantly lower scores were associated with second or third trimester exposures, or other exposure durations. In conclusion, exposure to opioid analgesics prenatally was associated with statistically significant, but small differences in fifth-grade test scores, for first trimester exposures and exposures in 2-3 four-week periods during pregnancy.
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