Some types of epilepsy medicine taken during pregnancy are associated with an increased risk of severe psychiatric disorders in children.

This is the conclusion of a comprehensive study of 38,000 children of mothers with epilepsy by researchers from Aarhus University.

While it has long been known that some forms of epilepsy medicine used during pregnancy are associated with a risk of birth defects, this new study is the most comprehensive study of children's mental health so far.

Among other things, the researchers found a worrying link between the antiseizure medication valproat and the child’s risk of developing a number of different psychiatric disorders.

"Our study shows that four out of ten children born to mothers with epilepsy who had used valproat during pregnancy were diagnosed with a psychiatric disorder before the age of 18, and that the drug was particularly associated with an increased risk of diseases such as autism, ADHD and intellectual disability," explains Jakob Christensen, a professor at Aarhus University and a consultant at Aarhus University Hospital and one of the researchers behind the study.

Warning against several drugs

In the study, 42 per cent of children of mothers who used valproat during pregnancy developed a psychiatric disorder before the age of 18. By comparison, only 31 per cent of children of mothers with epilepsy who did not take antiseizure medication during pregnancy developed a psychiatric disorder.

The study also shows that children whose mothers took the drugs topiramate or levetiracetam during pregnancy have an increased risk of ADHD and anxiety disorders.

On the positive side, the study shows that frequently used drugs such as lamostrigine, carbamazepine and oxcarbazepine are not associated with an increased risk of psychiatric disorders.

Need for more research

According to Jakob Christensen, the study confirms the existing warning against the use of valproate during pregnancy and also recommends caution with the use of topiramate and levetiracetam.

"Our research emphasises the importance of understanding the potential harmful effects of epilepsy medicine during pregnancy and the continued lack of knowledge about how different types of medicine can affect the child's psychological development,” he says and continues:

"Our study shows that there is a need for more research and more accurate risk estimates to help pregnant women with epilepsy and their doctors make informed decisions about the use of medicine during pregnancy."

The study was carried out across five Nordic countries – Denmark, Sweden, Norway, Finland and Iceland – and it includes children born in the period 1996-2017.

In Denmark, approx. 400 children are born every year to mothers who have taken epilepsy medicine during pregnancy.

The research results - more information

Type of study: Register-based cohort study

Partners: Aarhus University Hospital, University of Bergen, University of Oslo, Karolinska Institute, Western Norway University of Applied Sciences, University of New South Wales, University of Reykjavik, Norwegian Institute of Public Health, Finnish Institute for Health and Welfare.

External funding: NordForsk Nordic Program on Health and Welfare (83796; 83539) and Independent Research Fund Denmark (1133-00026B)

Potential conflicts of interest: The researchers have declared several possible conflicts of interest. Dr Bjørk has received fees from a company that has been approved to sell valproat, as well as remuneration and funding for her research from several pharmaceutical companies. Dr Alvestad has received remuneration for being a speaker for Eisai. Dr Igland has received funding for research from Pfizer and Sanofi. Dr Leinonen has received funding from the Inoovative Medicines Initiative, IMI ConePTION and the Finnish Medicines Agency. Dr Zoega has received funding from AbbVie Australia and is employed at the Center for Big Data Research in Health, University of New South Wales, which is also receiving funding from AbbVie Australia for research unrelated to this study. Dr Cohen and Dr Furu have received funding from the Research Council of Norway during the study. Dr Tomson has received funding from several pharmaceutical companies, and Jakob Christensen has received remuneration from UCB Nordic and personal remuneration from Eisai in connection with the study.

Link to publication: https://jamanetwork.com/journals/jamaneurology/fullarticle/2803245

Contact

Clinical Professor and Consultant Jakob Christensen
Aarhus University, Department of Clinical Medicine and the Department of Neurology at Aarhus University Hospital
jakob@clin.au.dk
Telephone: +45 60865899

Senior Researcher Julie Werenberg Dreier
Aarhus University, National Centre for Register-based Research
jwdreier.ncrr@au.dk
+45 87166204