In utero exposure to antiepileptic drugs (AEDs) in combination, or sodium valproate alone, is associated with a significant decrease in attainment in national educational tests for 7-year-old children, according to a study published in the Journal of Neurology, Neurosurgery, and Psychiatry.

Arron S. Lacey, from the Wales Epilepsy Research Network, Swansea University Medical School at Swansea University in the UK, and colleagues, used a databank to access routinely collected healthcare records and identify women who had been diagnosed with epilepsy before becoming pregnant. The authors defined a person as having a diagnosis of epilepsy if their general practitioner record contained an epilepsy diagnosis code, as well as a record of repeat AED prescriptions.

Between 1999 and 2011, children in Wales were assessed in 5 Key Stages (KS) tests between 7 and 16 years of age. All children were tested in mathematics, language (English or Welsh), and science and were awarded a level between 1 (lowest) and 3 (highest). The researchers linked these children to their national attainment KS1 tests at the age of 7 and compared them with matched children born to mothers without epilepsy, and with the national KS1 results. The core subject indicator (CSI) was used as an outcome measure (the proportion of children achieving a minimum standard in all subjects), as well as the results in individual subjects.

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The researchers identified 440 children with KS1 results available between 2003 and 2008 who had mothers with epilepsy diagnosed before their pregnancy. The authors defined 5 groups of mothers prescribed the following AEDs: monotherapy with carbamazepine, lamotrigine or sodium valproate, multiple AEDs, as well as no AED prescription.

Compared with a matched control group, fewer children with mothers being prescribed sodium valproate during pregnancy achieved the national minimum standard in CSI (-12.7% less than the control group), mathematics (-12.1%), language (-10.4%), and science (-12.2%). Even fewer children with mothers being prescribed multiple AEDs during pregnancy achieved a national minimum standard: CSI (by -20.7% less than the control group), mathematics (-21.9%), language (-19.3%), and science (-19.4%). The researchers did not observe any significant difference in children whose mothers were prescribed carbamazepine or were not taking an AED when compared with the control group.

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“Our results add to the growing evidence that in utero exposure to certain AEDs can cause developmental problems in children,” the authors concluded. “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.”


Lacey AS, Pickrell WO, Thomas RH, Kerr MP, White CP, Rees MI. Educational attainment of children born to mothers with epilepsy. J Neurol Neurosurg Psychiatry. [published online March 27, 2018]. doi: 10.1136/jnnp-2017-317515.