Anti-epilepsy drug sodium valproate is associated with developmental delay and lower IQ

The anti-epilepsy drug sodium valproate is associated with developmental delay and lower IQ, suggests research in the Journal of Neurology Neurosurgery and Psychiatry.

Around five in every 1000 people will have epilepsy. One in three people with epilepsy is a woman of childbearing age, and one in every 200 women attending antenatal clinics is being treated with anti-epileptic drugs.

The authors base their findings on a study of 375 children, 249 of whom were between the ages of 6 and 16 years. All the children had been born to mothers with confirmed epilepsy in Liverpool and Manchester, North West England.

The authors conducted structured interviews with the mothers about their epilepsy and any behavioural/developmental problems, including additional educational needs in their children, and checked hospital records.

They also clinically assessed the children and tested their intelligence, using a validated scoring system (Wechsler scale). And they assessed the degree of anatomical abnormality (dysmorphic features) from photographs.

All but 80 of the children had been exposed to anti-epilepsy drugs while in the womb: in 41 cases this was sodium valproate and in 52 it was carbamazepine. A further 21 children had been exposed to phenytoin, and the mothers of 49 had taken a mixture of drugs to control their epilepsy.

The children whose mothers had taken valproate alone had an IQ "in the low average range" and one that was significantly lower - an average of 7 points lower - than would have been expected.

A verbal IQ score of 69 or below was more than three times as likely in children exposed to valproate alone compared with those children whose mothers had not taken any anti-epileptic drugs.

Frequent seizures in the mother during pregnancy were also significantly associated with a lower verbal IQ. Valproate is very effective at controlling seizures in specific types of epilepsy, say the authors.

Dysmorphic features were more common among children whose mothers had taken valproate in pregnancy, affecting 44%, compared with 9% of those whose mothers had taken carbamazepine, and 2% among those whose mothers had not taken any drugs for epilepsy, while pregnant. There was a strong link between the degree of dysmorphism and the likelihood of significantly lower IQ.

The authors are quick to point out that there may be biases in their findings because only 40% of the 547 mothers originally approached responded, and they say that it is impossible to draw conclusions about absolute risk based on retrospective data.

Nevertheless, they conclude: "The results of our study are of concern given that valproate was first licensed in the United Kingdom in 1975."

Several new drugs have come on the market since then, they say, adding: "It is essential that adequately controlled prospective studies are established now to identify the level of risk for cognitive impairment in children of women taking both new and established [anti-epileptic drugs] during pregnancy."

An accompanying editorial by Simon Shorvon, of the Institute of Neurology, London, points out that caution is needed in interpreting the results, for the reasons stated by the authors. But he commends the authors for highlighting "what is potentially a major clinical concern," and for advising of the potential for anti-epileptic drugs to have a long term impact on intellectual development. "Further exploration of this vital area is now urgently needed," he says.

Click here to view the paper in full
Click here to view the editorial in full