Approximately 5,000 women with epilepsy become pregnant every year in the UK, and the vast of majority of these people, including those taking anti-epileptic drugs (AEDs), will suffer no complications. Research has shown, however, that children exposed to AEDs in the womb have an increased risk of defects such as heart malformation, cleft lip / palate and limb deformity. These are known as congenital abnormalities.

Studies on animals have shown that fetuses exposed to a lower dose of AED than that required to cause congenital abnormalities, have an increased risk of developing problems with behavior and mental processing (cognition). However, the cognitive effects of AED exposure in unborn humans have not been established.

Scientists at the University of Liverpool, the Central Manchester University NHS Foundation Trust and Emory University, in Atlanta, US, are conducting a multi-centre trial to explore this question.

Between 1999 and 2004, they enrolled pregnant women with epilepsy in the UK and US, who were taking one of four AEDs: carbamazepine, lamotrigine, phenytoin, or sodium valproate. Their main objective was to follow the babies from one to six years of age, to compare how their exposure to these AEDs affected their everyday lives. They were particularly interested in IQ, memory and language abilities. The mother's drug dosage, her age, her folic acid consumption and the pregnancy duration were all factored into the analysis.

The team also planned to carry out an interim assessment, looking specifically at 309 children at three years of age. This has been completed and the findings have been published in the New England Journal of Medicine.

The results showed that at three years of age, children who had been exposed to sodium valproate in the womb had significantly lower IQ scores than those who had been exposed to the other AEDs. The mean IQ was 101 for children exposed to lamotrigine, 99 for those exposed to phenytoin, 98 for those exposed to carbamazepine, and 92 for those exposed to sodium valproate.

On average, children exposed to sodium valproate had an IQ score 9 points lower than the score of those exposed to lamotrigine, 7 points lower than the score of those exposed to phenytoin and 6 points lower than the score of those exposed to carbamazepine . In addition, the effect of sodium valproate on IQ appeared to be dependent upon the dose taken by the mother.

Interestingly, the children's IQs were significantly related to their mothers' for those exposed to carbamazepine, lamotrigine and phenytoin, but this was not the case for children exposed to sodium valproate.

Commenting on the results, joint lead author Gus Baker, Professor of Clinical Neuropsychology at the University of Liverpool, said "The answer is not as simple as to take women off AEDs altogether, as the effects of suffering a seizure can also pose a risk for both mother and unborn child. It is vital that the research is now used to educate women with epilepsy before they start to plan for a family. Women need to be aware of the risks so that they can make informed choices with the help and advice of experts. It is also important that women do not stop taking AED treatment without taking advice from their medical practitioner."

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Professor Baker was one of our grant round winners this year, and he and his team will be looking at the effects of exposure to modern AEDs in the womb. To read more about his project, please click here