1. Any prenatal exposure to opioid analgesics was not associated with differences in school performance at the grade 5 level, compared with those whose mothers had only prepregnancy exposure.
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 only had exposure before pregnancy.
Evidence Rating Level: 2 (Good)
While an estimated 3 to 22% of pregnant individuals use prescription opioid analgesics, there is a lack of understanding of the neurological implications of prenatal exposure. A previous study found that high cumulative exposures or exposures longer than 14 days increased the risk of neurodevelopmental disorders, with risk ratios ranging from 1.22-1.70. The remaining three studies of prenatal exposure to opioid analgesics found no association with impaired language or communication skills, although exposure of 5 weeks or longer was associated with a greater risk of being diagnosed with ADHD (HR 1.60). Therefore, this current cohort study examined whether prenatal exposure, exposure time, or exposure duration were associated with differences in school skills at the fifth grade level. The study population consisted of 64,256 children born to 54,568 mothers, registered in a national birth registry between 2002 and 2008. The results were scores from national standardized tests for mathematics, Norwegian literacy and English language. The study found that 2.3% of pregnancies involved the use of opioid analgesics, and codeine with acetaminophen was the most common, reported by 90.5% of those with exposures. Of the students who were exempted from taking a test due to special needs, between 2.7% and 3.6% had exposure to opioid analgesics. In general, children with some exposure did not score lower on any test than children of mothers with only pre-pregnancy exposures. In terms of time of exposure, 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), compared to those of mothers with pre-pregnancy exposure alone. Finally, children born to mothers who used opioid analgesics during 2-3 four-week periods during pregnancy had lower literacy (wβ -0.13, 95% CI -0.25 to -0.01) and lower math skills (wβ -0.14, 95% CI -0.25 to -0.04) scores, compared to those of mothers with only pre-pregnancy exposure. No significantly lower scores were associated with second or third trimester exposures or other exposure durations. In conclusion, prenatal exposure to opioid analgesics was associated with statistically significant, but small differences in fifth degree test scores, for exposures in the first trimester and exposures in 2-3 four-week periods during pregnancy.
Click to read the study in JAMA Network Open
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