School Test Results Lower in Kids Exposed Prenatally to AED

Pauline Anderson

May 30, 2016

COPENHAGEN — Teens whose moms took valproate and other antiepileptic drugs (AEDs) during pregnancy lag behind their classmates in math and reading skills, according to preliminary results of a new study.

Previous studies looked at the cognitive effect of being exposed to these drugs prenatally but only up to about preschool age.

The new results were reported here by Lars S. Elkjær, research year student, Department of Neurology, Aarhus University Hospital, Aarhus, Denmark,at the 2nd Congress of the European Academy of Neurology.

For the study, Elkjær and his colleagues took advantage of the many linked Danish registries. From the birth registry, they constructed a cohort of all children born between 1997 and 2007, and from other registries they collected information on epilepsy diagnoses and all prescriptions filled for AEDs.

They also accessed data on school performance among the children. The Danish government introduced national tests in public schools across the country in 2010, said Elkjær. "All children enrolled in Danish public school are obligated to participate in these tests."

Danish reading tests are carried out at in the second grade, fourth grade, sixth grade (when the children are about 13 years old), and eighth grade. Mathematics tests are completed in the third and sixth grades.

Researchers "rescaled" the school test results to present them as standardized z-scores with a mean of 0 and a standard deviation of 1.

Children were considered "exposed" to an AED if their mother had taken one of these drugs between 30 days before conception and 1 day before birth, said Elkjær.

The study cohort includes 479,027 children who were tested from 2010 to 2014 (this doesn't include the youngest kids who were not yet in the second grade — the first year of testing).

The researchers adjusted the results for many possible confounders, including family income and the educational level of the mother, which, according to Elkjær, is one of the most important factors influencing how well kids perform in the school setting. They also adjusted for calendar year and the child's gender.

At the meeting here, Elkjær reported only the results from the sixth grade testing.

"Overall, the AED-exposed children performed significantly worse, especially the children exposed to valproate," compared with an unexposed reference group of children (who after standardization, performed at the mean of 0), said Elkjær.

For valproate, the adjusted mean z-score was –0.28 (95% confidence interval [CI], –0.41 to –0.14).

Interestingly, children exposed to clonazepam also performed significantly worse on these school tests than did unexposed kids.

However, lamotrigine-exposed children "are performing almost identically to the unexposed children," said Elkjær. The adjusted mean z-score for lamotrigine was 0.01 (95% CI, –0.01 to 0.04).

The children whose mothers took an AED during pregnancy did worse than unexposed children, whether or not the mother took the drug because of epilepsy. Elkjær later told delegates that it would be "a good idea" to learn what other diagnoses these women might have had.

Session co-chair Reeta Kälviäinen, MD, PhD, professor of clinical epileptology, University of Eastern Finland, Kuopio, Finland, commented that it's because of the Danish registries that such a study could be carried out. She also emphasized the importance of investigating the effect of prenatal valproate exposure in the teenage years.

"That is very important because, at the moment, we only know the effect of valproate at the preschool age, and there might be some catching up going on" among exposed children, she said.

Asked if a high dose of valproate had an even larger effect on cognitive skills in exposed children, Elkjær noted that not many children in the cohort were exposed to a high level of valproate. His research group has not yet done such an analysis but hopes to do so, he said.

Lars Elkjær has disclosed no relevant financial relationships.

2nd Congress of the European Academy of Neurology. Abstract O1109. Presented May 28, 2016.

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