Anti-Epilepsy Drug Use During Pregnancy Raises Risk For Autism: Study

Children of women who take an anti-epilepsy medication called valproate during pregnancy may be at a higher risk for autism, a new study suggests.

Danish scientists from Aarhus University Hospital were looking at the effects of maternal use of valproate, an anticonvulsant used in a number of conditions including epileptic seizures, manic episodes associated with bipolar disorder, and migraine headaches. Their results will be published in the Journal of the American Medical Association (JAMA) on Wednesday.

The researchers examined medical records for all children born alive in Denmark from 1996 to 2006 -- more than 655,000 in all. The children’s medical histories were followed for an average of nearly nine years after birth. Of these children, 5,437 were diagnosed with autism, and 2,644 were exposed to anti-epileptics; 508 children were exposed to valproate in the womb.

When the researchers ran the numbers, they found that prenatal valproate exposure was connected with an absolute risk for autism of 4.4 percent, meaning that around 4 out of every 100 children of mothers who took valproate during pregnancy were later diagnosed with autism.

"Children of women who used valproate during pregnancy had a higher risk of autism spectrum disorder and childhood autism compared with children of women who did not use valproate,” the researchers wrote. “Their risks were also higher than those for children of women who were previous users of valproate but who stopped before their pregnancy.”

The U.S. Food and Drug Administration already warns of potential cognitive effects for children of mothers taking valproate. Previous studies have shown that children with prenatal valproate exposure tend to score lower on IQ tests and other cognitive assessments than children born to mothers who took other kinds of antiseizure drugs. The long-term effects of the drug on children are not yet known.

"Because autism spectrum disorders are serious conditions with lifelong implications for affected children and their families, even a moderate increase in risk may have major health importance,” the authors wrote. “Still, the absolute risk of autism spectrum disorder was less than 5 percent, which is important to take into account when counseling women about the use of valproate in pregnancy."

In an accompanying editorial in JAMA, Emory University doctors wrote that doctors should be more proactive about warning pregnant women about the risks of valproate.

“Valproate is an effective drug, but it appears that it is being prescribed for women of child-bearing potential at a rate that does not fully consider the ratio of benefits to risks,” they wrote. In child-bearing women, “alternative medications should be sought. If no alternative effective medications can be found, the lowest effective dose of valproate should be used.”

How exactly could an antiseizure medicine result in autism?

It’s thought that many cases on the autism spectrum stem from some interruption or alteration very early on in development, at the point when an embryo’s neural tube -- the part that eventually gives rise to the brain and spinal cord -- is closing. In one 2005 review paper for the International Journal of Developmental Neuroscience, University of Rochester Medical Center researchers noted that exposing rat embryos to high doses of valproic acid (one of the forms of valproate) at the time of neural tube closure resulted in rodents with anatomic and behavioral similarities to autistic humans.

Other medications might affect early nervous system development too. In a study using data from Sweden’s national medical registry, researchers wrote of a possible link between autism spectrum disorders and antidepressant use during pregnancy.

“Why should it surprise us that medications that can change brain chemistry and function might alter the development of the brain and behavior?” Tufts University obstetrician Adam Urato told the New York Times on Monday.