In utero exposure to some antiepileptic drugs was linked to decreased educational achievement at the age of 7 years, in results of a matched-case control study.

Compared with controls, children exposed in the womb to sodium valproate alone, or to multiple antiepileptics (AEDs), had lower scores on U.K standardized tests routinely administered to 7-year-olds, according to results published in the Journal of Neurology, Neurosurgery & Psychiatry.

The results provide evidence showing that in utero exposure to some AEDs may lead to developmental issues in children, according to lead author Arron S. Lacey, Wales Epilepsy Research Network, Swansea University Medical School, Swansea, England, and coauthors.

“Women with epilepsy should be informed of this risk, and alternative treatment regimens should be discussed before their pregnancy with a physician that specializes in epilepsy,” Dr. Lacey concluded in a discussion of their study results .

In the United Kingdom, already-stringent guidance on valproate in pregnancy was strengthened on March 23 when the European Medicines Agency announced new measures designed to avoid valproate exposure in pregnancy because of risk of malformations and developmental issues. The measures include a ban on valproate-containing medicines for the treatment of epilepsy during pregnancy unless no other effective treatment in available.

The risks of AEDs, and valproate in particular, in pregnancy have been documented in multiple studies suggesting that exposure may lead to cognitive impairment, neurodevelopmental disorders, and impaired IQ. However, the available data are largely from psychometric studies, Dr. Lacey and colleagues noted in their report. “It is important to know whether the psychometric differences demonstrated in research conditions translate to children in the community,” they wrote.

To address this, Dr. Lacey and coinvestigators conducted a study of standardized academic test results in children in Wales born to mothers with epilepsy who had been prescribed AEDs during pregnancy. They reviewed health records and identified 440 AED-exposed children who had available results for Key Stage 1 tests for mathematics, language and science at the age of 7 years.

Among children whose mothers had been prescribed valproate during pregnancy, the proportion achieving U.K. minimum standards for all subjects was 12.7% lower than a matched control group, investigators said.

Children of mothers who had been prescribed multiple AEDs had an even lower proportion achieving the minimum standard for all subjects, at 20.7% less than the control group, they added.

By contrast, children whose mothers were prescribed carbamazepine did not have any significant differences in educational achievement, compared with controls.

Some previous studies found as association between exposure to carbamazepine and cognitive impairment, while others found no such association. “Our study supports the latter, with no evidence of decreased educational attainment at school age,” the investigators said in their article.

Some study authors reported competing interests related to Eisai, Sanofi, UCB, and others.

SOURCE: Lacey AS et al. J Neurol Neurosurg Psychiatry. 2018 Mar 25. doi: 10.1136/jnnp-201-317515 .


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