New research shows that, at an early stage, Danish healthcare registries can identify risk of congenital malformations in children when the mother has taken the epilepsy drug valproate during pregnancy.

Today, we know there is an increased risk of congenital malformations in children if the mother has taken the epilepsy drug valproate during pregnancy. Since 2009, the Danish Medicines Agency has warned not to use valproate during pregnancy and to use the drug only in exceptional cases for women of childbearing age.

Before 2009, could the risk then have been identified earlier and thus prevented children to be  born with congenital malformations due to the mother’s use of valproate? Researchers at Aarhus University Hospital and Aarhus University in Denmark have studied this question by going through registrations of children with major congenital malformations born between 1997 and 2014 and compared this information with the issuing of prescriptions for epilepsy medicine.

Data on pregnancies, consumption of medicine and congenital malformations in children born in 1997 showed an increased risk of congenital malformations if mothers had been exposed to valproate during pregnancy. Over the years and thus an increasing amount of data, this risk became statistically significant.

The risk of malformations was increased both compared with children who had not been exposed to maternal use of epilepsy medicine during pregnancy and compared with children of mothers who had used other types of epilepsy medicine during pregnancy.

- Our research shows that data in the Danish healthcare registries could have made it possible to identify the risk of fetal malformations if the mothers used valproate during pregnancy, says Jakob Christensen, Consultant at Aarhus University Hospital and Associate Professor at Aarhus University. Jakob Christensen is a specialist in both neurology and clinical pharmacology, and he has for many years worked with Danish registries in his research.

- This is an important example of how Danish registries can contribute to identify risks in connection with exposure to medicine during pregnancy faster than traditional follow-up studies. The advantages are obvious if researchers can get fast access to updated data from the registries.

The researchers collected registry data on children born in Denmark between 1 January 1997 and 31 December 2014 and their mothers. Data on use of epilepsy medicine were retrieved from the Danish Prescription Register. Data on children with major congenital malformations were identified in the National Patient Register and the Danish Register of Causes of Death.

Behind the research result:

Study type: Registry study based on health registries

Collaborators: Center for Register-based Research and Centre for Integrated Register-based Research, Aarhus University, Haukeland University Hospital and Karolinska University Hospital

External funding: The Epilepsy Association, Central Denmark Region, the Novo Nordisk Foundation and Danish National Research Foundation

Conflicts of interests: Jakob Christensen has received a fee for being on the Scientific Advisory Board of UCB Nordic and Eisai AB, and a fee for presentations for UCB Nordic and Eisai AB and travel expenses financed by UCB Nordic. Nils Erik Gilhus has received a fee from UCB, Roche; Ra; Argenx, Alexion, Immunovant and Merck. Torbjörn Tomson has received a grant from Eisai, GSK, UCB, Bial, GW Pharma, Teva and Sanofi, as well as a fee to Karolinska from Eisai, Sanofi, Sun Pharma, UCB, Arvelle and GW pharma for projects unrelated to the present study.

Read the scientific article:

Jakob Christensen, Betina Trabjerg, Yuelian Sun, Nils Erik Gilhus, Marte H. Bjørk, Torbjörn Tomson og Julie Werenberg Dreier. Prenatal exposure to valproate and risk of congenital malformations – Could we have known earlier? – a population-based cohort study. EPILEPSIA. 2021 Sep 28. DOI: 10.1111/epi.17085.

Further information:

Jakob Christensen, MD, Consultant
Department of Neurology, Aarhus University Hospital
Associate professor, Department of Clinical Medicine, Aarhus Universitye
Tel.: +45 6086 5899, e-mail: jakob@farm.au.dk