A Pregnancy Dilemma for a Medication?

Antiepileptic valproate during pregnancy linked to higher risk of autism in children

/ Author:  / Reviewed by: Joseph V. Madia, MD

(RxWiki News) Some medications are linked to disorders such as autism or to birth defects when taken during pregnancy. However, that risk must also be balanced against the medication's benefits.

A recent study found that a medication called valproate was linked to a higher risk of autism in children when the children's mothers took it during pregnancy.

Valproate can be prescribed to treat epilepsy, mood disorders and other conditions.

Taking valproate was linked to higher autism rates even after researchers took into account a mother's epilepsy diagnosis.

"Discuss all meds with your care providers."

The study, led by Jakob Christensen, PhD, of the Department of Neurology at Aarhus University Hospital in Denmark, looked for links between valproate exposure during pregnancy and children's risk of autism.

The researchers looked at national registry data for all children born in Denmark between 1996 and 2006 to identify children born with autism spectrum disorders, including Asperger's syndrome, atypical autism and other or unspecified pervasive developmental disorders.

Out of 655,615 children born during that decade, 5,437 were diagnosed with autism spectrum disorder at some point. Childhood autism was diagnosed in 2,067 of the children.

The researchers also identified all the children whose mothers had taken valproate while pregnant.

Valproate is an anti-epilectic drug that can be used to treat seizures, epilepsy, migraine prevention and both manic and mixed bipolar disorder. It is known by the brand name Depacon or Depakote.

Past research has already found increased risks for spina bifida in children whose mothers took valproate during pregnancy.

The researchers compared the risk of autism spectrum disorders among children who had and had not been exposed to valproate while in the womb.

Overall, 1.53 percent of the children born during that time period were diagnosed with autism spectrum disorder, and 0.48 percent were diagnosed with childhood autism.

Of the 508 children exposed to valproate before being born, 4.42 percent were diagnosed with autism spectrum disorder, and 2.5 percent of them were diagnosed with childhood autism.

The researchers also adjusted their calculations to account for both parents' ages when they conceived their child, both parents' psychiatric history, the pregnancy week when the baby was born, the child's birth weight and sex, whether the child had any birth defects and how many children the mother had previously had.

After this adjustment, children born to women who took valproate during pregnancy were at about three times higher risk for having autism spectrum disorder and five times higher risk for having childhood autism.

The researchers also looked at the rates of autism only among the 6,584 women who had epilepsy, a condition which is often treated with valproate.

Overall, 432 of the mothers with epilepsy had taken valproate, and 4.15 percent of their children had autism spectrum disorder, compared to 2.44 percent of children with autism spectrum disorder born to epileptic mothers who did not take valproate.

The children whose mothers had epilepsy and took valproate were at a 70 percent higher risk (almost twice the risk) of having autism spectrum disorder than children born to mothers who did not take valproate.

Also among the women with epilepsy who took valproate, 2.95 percent of their children had childhood autism, compared to 1.02 percent of children with childhood autism born to epileptic mothers who did not take valproate.

Children born to mothers with epilepsy who took valproate were therefore at a three times higher risk of childhood autism compared to the children whose mothers did not take valproate.

Overall, therefore, the researchers found that a mother's taking valproate during pregnancy was associated with a higher risk of autism in her children, even after taking into account whether she had epilepsy.

“This study is well constructed and makes excellent use of the Scandinavian extensive, essentially complete information related to the health and well-being of its citizens," said dailyRx expert Glen Elliott, MD, PhD, a clinical professor at the Stanford University Department of Psychiatry and Behavioral Sciences.

"A reported five-fold increase from the use of valproic acid during pregnancy in the absolute risk of having a child with an autism spectrum disorder undoubtedly will affect future decision making about the use of this anti-convulsant in pregnant women, especially given that a number of other anti-convulsants also included in the study carried no such increased risk," Dr. Elliott said.

However, he cautioned that using the study to understand the underlying causes of autism may be less helpful.

"Speculation about whether this finding may help bring the field closer to an understanding of one possible [cause] of autism, presumably through effects on folic acid, are intriguing but much less definitive," Dr. Elliott said. "Still, overall, this is a finding that is apt to help both expectant mothers and their physicians to make important treatment decisions.”

This finding also does not mean that women taking valproate should stop after they become pregnant. Some women may require this medication to control their symptoms of epilepsy, bipolar disorder or another condition.

"For women of childbearing potential who use anti-epileptic medications, these findings must be balanced against the treatment benefits for women who require valproate for epilepsy control," the authors wrote.

The study was published April 24 in JAMA.

The research was funded by grants from the European Research Council (the European Union Seventh Framework Programme) and the Danish Medical Research Council. The researchers were also supported by the Danish Epilepsy Association and a Sapere Aude–Postdoctoral grant from the Danish Council for Independent Research.

One author has received honoraria from UCB Nordic and Eisai AB for lectures and serving on the scientific advisory boards; he has also received travel funds from UCB Nordic. Another author has received grants from Autism Speaks and the National Institutes of Health. No other conflicts of interest were reported.

Reviewed by: 
Review Date: 
April 24, 2013
Last Updated:
November 12, 2013