Previous studies have shown that women who have taken certain medications for epilepsy during pregnancy give birth to children with a low birth weight given the gestational week of birth. For some of the medications available the risk has been known and clear, but for others the available knowledge regarding the risks has been somewhat limited or unclear.

Therefore, epileptologists and researchers from Denmark, Finland, Iceland, Norway, and Sweden have compared the birth weight and duration of gestation of 4,494,918 Nordic children with information about whether the mother has been prescribed drugs for epilepsy during their pregnancy.

Over a 20-year timeframe

The study is the world's largest of its kind and is led by chief physician at Aarhus University Hospital and professor at Aarhus University, Jakob Christensen, and senior researcher Julie Werenberg Dreier from the National Centre for Register-based Research at Aarhus University.

This study included 38,714 children of mothers who suffer from epilepsy. The results show that children of mothers who received carbamazepine, oxcarbazepine, clonazepam and topiramate were more likely to be born with a low birth weight given their gestational week of birth. Furthermore, the medicine carbamazepine was also associated with the baby having smaller head circumference when born.

- The results indicate that the use of these drugs in pregnancy is associated with growth restriction of the fetus. This is concerning due to the increased risk of complications during pregnancy and birth associated with fetal growth restriction, as well as a higher risk of disease later in life, says chief physician and professor Jakob Christensen.

Important information for patients and doctors

The researchers could not find any association between the use of lamotrigine, valproate, gabapentin or levetiracetam during pregnancy and the risk of children being born with low birth weight or head circumference for their gestational week of birth. The same was true for nine other epilepsy medications, but the number of children exposed to these nine medications was too small to produce reliable risk estimates.

- In addition to the size of the study, which has made it possible to look at both new and rarely used types of epilepsy medication, the major strengths of this study are that the results are representative of pregnant women across the Nordic countries, and that we were able to adjust the results for potential confounders e.g. socioeconomic conditions and certain lifestyle factors, such as the mother's smoking habits and weight. These are factors that could otherwise potentially distort the results if they are not adequately accounted for, says senior researcher Julie Werenberg Dreier.

- The results provide important information for patients and doctors, helping with decision making and treatment planning when addressing the complex situation involving the medical treatment of pregnant women with epilepsy and the possible risks to the foetus, says Professor Jakob Christensen.

Behind the research results

Type of study: Population-based cohort study

Collaborators: Universities and state research institutes in Reykjavik, Helsinki, Bergen, Stockholm and Sydney.

External funding: NordForsk, Independent Research Fund Denmark, The Danish Epilepsy Association, Central Denmark Region, Novo Nordisk Foundation and Lundbeck Foundation.

Conflicts of interest: The authors' conflicts of interest are declared in the article.

Read the scientific article:

Jakob Christensen, Helga Zoega, Maarit K. Leinonen, Nils Erik Gilhus, Mika Gissler, Jannicke Igland, Yuelian Sun, Torbjörn Tomson, Silje Alvestad, Marte-Helene Bjørk and Julie Werenberg Dreier. Prenatal exposure to antiseizure medications and foetal growth: a population-based cohort study from the Nordic countries. The Lancet Regional Health – Europe. 2024; 38: 100849. Published online: 08. February 2024 https://doi.org/10.1016/j.lanepe.2024.100849

For more information:

Jakob Christensen
Chief Physician, Neurology, Aarhus University Hospital
Professor at the Department of Clinical Medicine, Aarhus University
Phone +45 6086 5899, e-mail: jakob@farm.au.dk                

Julie Werenberg Dreier
Senior researcher at The National Centre for Register-based Research at Aarhus BSS at Aarhus University
Phone +45 2562 1178, e-mail: jwdreier.ncrr@au.dk