5-6-09 | Valproate in pregnancy may lower child's IQ

05 June 2009
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A new study published in the New England Journal of Medicine has found that the commonly prescribed epilepsy drug Valproate should not be used in women who may become pregnant.

The recommendation is based on a 3-year analysis of results from the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study. The study found that in utero exposure to valproate is more likely to impair cognitive development than other commonly used antiepileptic drugs.

NEAD is an ongoing study in the US and the UK which aims to determine the long-term neurodevelopmental effects of 4 commonly used antiepileptic drugs: carbamazepine, lamotrigine, phenytoin, and valproate.

In the study, investigators looked at 309 children overall and found that at 3 years of age, children who had been exposed to valproate had significantly lower IQ scores than those who had been exposed to other antiepileptic drugs. This was the case even after adjustments were made for maternal IQ, maternal age, drug dose and gestational age at birth. The effect of the drug on IQ also seemed to be dose-dependent.

The average IQ was 92 for children exposed to valproate but between 98 and 101 for the other three drugs examined.

"The present results, together with other data , suggest that valproate should not be used as a first-line antiepileptic drug in pregnant women or -- since data indicate that half of pregnancies are unplanned -- in women of childbearing potential," the authors state.

In 2006, another study was published in the journal Neurology stating that approximately 20% of babies born after the mother took valproate suffered serious adverse outcomes, including fetal malformations, autism, spina bifida and decreased thinking ability compared with other drugs that had lower rates between 1% and 11%.

Guidelines issued by the American Academy of Neurology and American Epilepsy Society on foot of the new study confirm that pregnancy is relatively safe for women with epilepsy, but they recommended that in addition to avoiding valproate, they may also want to take other precautions including:

  • Avoid taking more than one anti-epileptic drug.
  • Avoid taking phenytoin and phenobarbital, which also have been linked to decreased thinking ability in offspring.
  • Stop smoking
  • Have blood tested regularly to adjust any medications for the risk of seizures
  • Take at least 400 micrograms of folic acid every day

It should be noted that the numbers involved in the study were quite low and that there was no control group involved in the study. As a result, some experts are now calling for additional larger studies to confirm the results.

Nevertheless, the study highlights the importance of pregnancy planning for women with epilepsy. It reinforces the need for women with epilepsy to get advice on the most appropriate AED for them before they become pregnant. The ideal situation is to be on one anti-seizure medication and to be on the lowest dose possible during pregnancy.

For doctors, this study becomes a factor when selecting an antiepileptic-drug for women with epilepsy who are of childbearing potential. The challenge is to find a treatment that is effective in controlling seizures but has minimal associated risks.

Most women with epilepsy need to continue taking medication during pregnancy, since uncontrolled seizures can be harmful. Women should never stop taking epilepsy medication without consulting their doctor as this could be potentially harmful to their health and their unborn child.

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