Women who take valproic acid for epilepsy while pregnant are twice as likely to have children with autism spectrum disorder, a study has suggested.
The study published in Neurology
, the medical journal of the American Academy of Neurology, also found that taking valproic acid while pregnant increases the risk of having children with attention deficit hyperactivity disorder (ADHD) by nearly two-fold.
Using data from Sweden, the researchers followed 14,613 children, born between 1996 and 2011, until 2013. They found that use of anti-seizure medication during the first trimester had occurred in 22.7% of pregnancies, of which the most common were valproic acid (4.8%), lamotrigine (6.8%) and carbamazepine (9.7%). The researchers then identified cases of autism spectrum disorder and ADHD in the children.
After adjusting for confounding factors, the researchers calculated that use of valproic acid was associated with a more than two-fold increased risk of autism spectrum disorder (hazard ratio = 2.30, 95% confidence interval [CI] 1.53-3.47) and an almost two-fold increased risk of ADHD (HR = 1.74, 95% CI = 1.28-2.38).
A small association was found between carbamazepine and autism spectrum disorder and ADHD, but the link was not statistically significant. For lamotrigine, all of the associations with the two disorders were explained by confounding factors.
The authors said that the findings added to the “growing body of evidence” that suggested that certain anti-seizure medications may be safer than others in pregnancy. However, they said that it was important to interpret the elevated risk of autism and ADHD in children “with caution”, as it was not possible to rule out all sources of confounding in the study.
“Although findings may be consistent with a causal effect, the independent associations could be confounded by the severity of epilepsy or other indications of use which our study was not able to account for.”
In July 2020, a survey by three epilepsy charities found that just under half of pharmacists were not discussing the risks of taking sodium valproate when dispensing the drug to women, and just over half of pharmacists were not providing a patient card warning of the risks.
Both these actions are recommended by the Medicines and Healthcare products Regulatory Agency (MHRA), which introduced the advice in 2018 owing to the risks of birth defects if the antiepileptic drug is taken during pregnancy.
At the same time, the Independent Medicines and Medical Devices Safety Review published a report on the experiences of women who had been given valproate. In the report, it said that the MHRA’s advice needed “substantial revision” in terms of adverse event reporting.
A spokesperson for the MHRA told The Pharmaceutical Journal that it is “taking the findings of the report extremely seriously”.
“The agency is in the process of carefully studying the findings and recommendations of the report, and are working with the Department of Health and Social Care, who are leading the government response to the report.”