Women with epilepsy who consider having children have a difficult dilemma. Unmedicated, they can experience epileptic seizures and risk serious injury. Conversely, antiseizure medication may be associated with the development of autism and intellectual disability among children. The largest study so far has now scrutinised individual types of antiseizure medication. Two of the most common types are associated with an increased risk of autism and intellectual disability, and a combination of two others is largely not associated. The researcher behind the study says that using the new knowledge can ensure the health of both the mother and her child.
Women with epilepsy need medication to prevent seizures – even during pregnancy. Previous studies have shown a 3- to 5-fold increased risk of developing autism spectrum disorder and intellectual disability among children after prenatal exposure to valproate. However, these studies have not clarified whether other types of antiseizure medication and combinations thereof are associated with the same level of risk. A new study has clarified this.
“Our new study includes more than 4 million mother-child pairs from health registries in Norway, Sweden, Finland, Iceland and Denmark. The results show that children exposed to certain types of antiseizure medication have a 2- to 4-fold increased risk of autism spectrum disorder and intellectual disability compared with other children. This is important new knowledge for doctors and for women with epilepsy,” explains Jakob Christensen, a consultant at Aarhus University Hospital and Associate Professor at Aarhus University.
No elevated risk for type most commonly used during pregnancy in Denmark
The fact that antiseizure medication can strongly affect the children of mothers who take it during pregnancy has long been known. Taking valproate during pregnancy is clearly associated with physical disorders among children. However, researchers have also been scrutinising an association with an increased risk of autism and other neurodevelopmental disorders.
“Pregnant women with epilepsy often need antiseizure medication to prevent seizures. Data from health registries from the Nordic countries show a more nuanced picture of the risk associated with all types and combinations of antiseizure medication used by pregnant women with epilepsy between 1996 and 2017,” says Jakob Christensen.
The researchers collected registry data on almost 4.5 million children: 24,825 were born to mothers who used antiseizure medication during pregnancy, and 2,892 of these were born to mothers who specifically used topiramate and valproate.
“These types of antiseizure medication were associated with a 2- to 4-fold increased risk of developing autism spectrum disorders and intellectual disabilities. The study also confirms results from previous studies that the drug pregnant women with epilepsy most commonly use in Denmark – lamotrigine – is not associated with these risks,” explains Jakob Christensen.
Switch drugs early
The new study is the largest so far and strongly confirms the association between prenatal exposure to antiseizure medication and an increased risk of autism and intellectual disability. The new knowledge confirms previous studies and is important knowledge for doctors and for women with epilepsy.
“Five in 1000 pregnant women take antiseizure medication. Previous studies have shown that pregnant women with epilepsy have higher mortality than those without epilepsy. Women with epilepsy who do not take medication during pregnancy risk seizures, which have been associated with increased mortality. This is why understanding the risk to the child and the types of antiseizure medication to which a woman can switch to ensure her health and that of her child is so important,” says Jakob Christensen.
Combining two types of epilepsy medication in duotherapy may be a good solution since some women still have seizures when using only one type. Duotherapy can therefore protect the mother and help to ensure that the child is not exposed to increased risk.
“Unfortunately, some of the common duotherapies, including levetiracetam + carbamazepine and lamotrigine + topiramate, are associated with an increased risk similar to valproate. However, duotherapy with levetiracetam + lamotrigine was not associated with increased risk, so good alternatives exist,” adds Jakob Christensen.
The researchers do not fully understand the reasons for the specific effects. Although valproate has been one of the most widely used antiseizure drugs for decades, its effect has not been fully elucidated. However, it is known to affect DNA molecules when cells divide, which could explain the strong effects in early fetal development.
“Our study emphasises that women of reproductive age with epilepsy should only use valproate if no other treatment has an equivalent effect. Based on our results, we would clearly recommend that fertile women avoid using valproate if possible and that if they do, before a planned pregnancy, switch to a safer drug because switching drugs in pregnancy can be problematic and can have strong effects,” concludes Jakob Christensen.
