Valproate is a prescription medication sold under the name of Depakene in the US, Epilim in Great Britain, and other names elsewhere. It was introduced as a drug for seizure disorders, and is widely used especially for absence seizures and partial seizures.
Already Known To Be Teratogenic
Valproate is known to increase the risk of neural tube and other defects in babies of pregnant women taking the drug. Drug companies are required to include a “Black Box Warning” in the packaging about the risk to the fetus, and also about risk of liver damage to anyone taking it.
How Valproate Works
Valproate is believed to act primarily by affecting GABA, a brain chemical. GABA generally is an inhibitory neurotransmitter. Valproate also blocks folate, which is probably its mechanism for causing neural tube defects.
The Study
This study from Great Britain was reported in the December 2, 2008 journal Neurology. Scientists at the University of Liverpool followed about 250 very young children whose mothers had taken medications for epilepsy, and about 300 control children (whose mothers did not take anti-epilepsy drugs). The children were evaluated regularly. Of the children who were found to have autism, the mothers were more likely to have taken valproate. Results so far are considered interim, as the study is not over.
Implications
The study is not complete yet, so it’s value so far is only cautionary. It describes another possible risk from valproate use in pregnancy. But the risk is just that—a risk, a small chance. In this particular study, 64 children had been exposed to valporate and four of those developed autism, about a 6% chance. Women need to weigh the risks against the risk of a seizure in pregnancy. It can be a difficult risk vs. risk decision
Signs of autism may include repetitive behaviors, social difficulties, restricted interests, and mental retardation Autism occurs in about one in 150 births, and is thought to have a genetic component. The autistic children in this study did not have a family history of autism, which may make the findings less likely to be by chance alone.
In utero exposure to other teratogenic drugs such as thalidomide and alcohol are known to increase the risk of autism. Animal studies and case reports suggest that anti-epilepsy drugs may, also. This study is possibly the first systematic examination of the risk.
Source: Bromley RL, et al. Neurology Dec 2, 2008; 71:1923-24
