Does Prenatal Opioid Analgesic Exposure Affect Kids’ Scholastic Outcomes?

Prenatal exposure to opioid analgesics had no substantial impact on the scholastic skills of children by the time they reached fifth grade, findings from a nationwide Norwegian birth cohort suggested.

Compared to children of mothers whose only exposures to opioids were prior to pregnancy, children exposed in the first trimester and those exposed in two or three 4-week intervals during pregnancy scored lower on fifth grade 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; respectively) and numeracy (wβ -0.14, 95% CI -0.25 to -0.04; and wβ -0.19, 95% CI -0.34 to -0.05), reported Johanne Naper Trønnes, MSc, Pharm, of the University of Oslo, and colleagues.

But “these differences were small and may not be clinically relevant,” according to the researchers, writing in JAMA Network Open.

The group noted that scholastic skills are important indicators of cognitive function, but are only rarely assessed in perinatal pharmacoepidemiologic studies, and that most prior studies involving opioids have been conducted with women who used them as maintenance therapy, or for illicit purposes.

“Our results suggest that prenatal exposure to opioid analgesics was not associated with poor fifth-grade scholastic skills,” the investigators wrote. “These findings may be useful for physicians advising pregnant women who need opioid analgesics for pain management.”

Writing in an accompanying editorial, Victor Volovici, MD, PhD, of Erasmus MC University Medical Center in Rotterdam, The Netherlands, and colleagues said the new study provides “the medical community with potentially useful news,” but also sounded a note of caution and questioned the generalizability to U.S. medical practice.

“The substantial population differences and the fact that this study lacks information on the exact type of opioid use and dosage precludes a comparison with the current practice in the U.S.,” the editorialists wrote. “However, this study does convincingly suggest that careful prescription of largely weak opioids in pregnancy need not affect the scholastic performance of the offspring.”

The study included 64,256 children of 54,586 mothers (mean age 30.5) who had reported pain during pregnancy, with data obtained from the Norwegian Mother, Father, and Child Cohort (1999-2008), and then linked to the Medical Birth Registry of Norway and data from Statistics Norway. Opioid analgesic use was reported in 1,483 pregnancies (2.3%).

All children were ages 10-11 years old at the time of their fifth grade assessment. The tests provided to the children were national mandatory standardized tests that focused on numerical, literacy, and English language skills. Children with special language or educational needs were excluded. “Test scores were standardized as z scores over the total population of children taking the tests in each subject and for each test year,” explained Trønnes and colleagues. “A z score of -1 indicated a test score of 1 SD lower than the population mean.”

Only 13% of the children included in the cohort analysis scored 1 SD lower than the national average, with no statistically significant differences between children who were exposed during pregnancy and those whose mothers were exposed prior.

Mothers self-reported their opioid use via both prenatal and postpartum questionnaires, providing information about the timing of when they took the medication, as well as any illnesses. Opioid exposure was categorized by both the timing and duration of medication use.

The most common type of opioid use was a combination of codeine with acetaminophen, ultimately used by 90% of the mothers who reported opioid use in the study.

Study limitations, Trønnes and co-authors said, included that scholastic skills were measured at just one time point. In addition, reporting of opioid medication use is known to be influenced by accuracy of recall and willingness to report and thus may be subject to misclassification.