Analysis of Prenatal Exposure to Opioid Analgesics and Scholastic Skills in Children in Fifth Grade in Norway

Abstract

Importance Few studies have examined the neurodevelopmental consequences of prenatal exposure to opioid analgesics. Therefore, it is necessary to gain knowledge to inform clinical decisions for pregnant women with moderate to severe pain.

Objective To investigate fifth-grade scholastic skills in children with prenatal exposure to opioid analgesics.

Design, Setting, and Participants A cohort study was conducted based on data from the Norwegian Mother, Father, and Child Cohort (1999-2008). These data were linked to the Medical Birth Registry of Norway, and data from Statistics Norway included 64 256 live-born singletons, born to 54 568 mothers who reported pain during pregnancy, were analyzed. The study was conducted from July 1 to December 15, 2021.

Exposures Self-reported exposure to opioid analgesics during pregnancy, characterized in terms of any exposure, the exposure timing, and the exposure duration.

Main Outcomes and Measures Scores from 3 national tests for children in fifth grade. The tests measured scholastic skills in literacy, numeracy, and the English language. Test scores were standardized to z scores. Differences in z scores were compared between children of mothers exposed to opioid analgesics during pregnancy and children of mothers with only prepregnancy opioid exposure.

Results Of the 64 256 children included, 32 521 were boys (50.6%), and 1483 children (2.3%) were exposed to an opioid analgesic at least once during gestation. All test scores were similar between children with any exposure to opioid analgesics in utero and children with only prepregnancy exposure. Children exposed in the first trimester and those exposed in two or three 4-week intervals during pregnancy scored lower than children of mothers with only prepregnancy exposures on tests in literacy (weighted β [wβ], −0.13; 95% CI, −0.25 to −0.01 and wβ, −0.19; 95% CI, −0.35 to −0.04) and numeracy (wβ, −0.14; 95% CI, −0.25 to −0.04 and wβ, −0.19; 95% CI, −0.34 to −0.05). These differences were small and may not be clinically relevant.

Conclusions and Relevance In this large birth cohort, prenatal exposure to opioid analgesics had no substantial negative association with fifth-grade scholastic skills. However, adequate pain management in pregnancy may be addressed on an individual patient level, bearing in mind the benefits and risks of different analgesic therapies.