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Further Evidence that Valproate during Pregnancy Increases Autism Risk

Large study links autism and prenatal use of anti-epileptic drug; alternative medicines possible for some but not all women

For over a decade, studies have suggested a link between autism and the use of the anti-epileptic drug valproate during pregnancy. Today, the Journal of the American Medical Association (JAMA) published the results of the largest-ever study to address this concern.

The researchers studied the national health registry records of all Danish children born between 1996 and 2006. Out of a total of 655,615 children, 508 were born to mothers taking valproate during pregnancy.

The study found that prenatal exposure to valproate nearly tripled the risk of autism spectrum disorder (ASD). ASD prevalence was 4.4 percent (just under 1 in 20) among the children whose mothers took valproate during pregnancy. This compared to 1.5 percent (1 in 66) across all the children in the study. The researchers emphasized this increased risk remained relatively low – still under 5 percent. They saw a less-pronounced increase in autism risk among children whose mothers had used valproate but stopped before pregnancy.

Of additional interest, the prenatal valproate exposure appeared to change the ratio of boys to girls affected by autism. In the general population, autism affects four times as many boys as girls. Among those exposed to valproate in this study, autism affected just twice many boys as girls. Further research is needed to understand this effect.

The study did not find increased autism risk with other anti-epilepsy therapies. However, these alternatives don’t work for all patients. As such, the researchers emphasized that the increased risk of autism must be balanced against the benefits to women who need valproate to control their epilepsy. 

Jakob Christensen, Ph.D., of Denmark’s Aarhus University Hospital led the study. The analysis controlled for factors that might skew outcomes. These included parental age and psychiatric history, prematurity, birth weight and birth defects.

JAMA published a related editorial by neurologist Kimford Meador, M.D., and neuropsychologist David Loring, Ph.D., of Emory University, in Atlanta. They noted that prenatal use of valproate has also been linked to birth defects and mental impairments. As such, they urged doctors to discuss valproate’s risks and benefits with their patients and consider alternative medicines. If no effective alternatives can be found, they recommend using the lowest effective dose of valproate.

“As the largest study to date identifying valproate as a risk factor for ASD, this research contributes to our understanding of environmental risk factors associated with autism,” adds Alycia Halladay, Ph.D., Autism Speaks senior director of environmental and clinical research. “Further research is needed. If scientists can identify the mechanism by which valproate affects risk, then prevention measures may be taken.”

The Epilepsy Foundation has more information on pregnancy and epilepsy medications here.