Large study: certain antiseizure medications associated with lower birthweight

Disease and treatment 9. apr 2024 3 min Clinical Professor Jakob Christensen, Senior Researcher Julie Werenberg Dreier Written by Morten Busch

A new comprehensive study analysing health data from 4.5 million children in the Nordic countries found associations between using certain antiseizure medications during pregnancy and lower birthweight. This emphasises the need for carefully assessing antiseizure medications for pregnant women with epilepsy to ensure optimal outcomes for both the mother and the child.

Pregnant women with epilepsy often face the dilemma of which medication to take during pregnancy and how this affects the health of their unborn child. Previous research indicates that some antiseizure medications can affect fetal growth, but data have been limited. A new study of 4.5 million children born in the Nordic countries investigated the associations between maternal use of several antiseizure medications during pregnancy and the child’s birthweight. The results improve decision-making for choosing antiseizure medications in pregnancy.

“The study reveals that the children born to mothers who took different antiseizure medications during pregnancy differed in birthweight. Some medications were not associated with a risk of low birthweight and others were. This suggests that some antiseizure medications may affect fetal growth and development, emphasising the need for individualised treatment based on thorough risk assessment,” explains a lead author, Jakob Christensen, Chief Physician, Aarhus University Hospital and Professor, Department of Clinical Medicine, Aarhus University, Denmark.

Largest study of its kind

Previous studies assessed the risk of children having congenital malformations or developmental disorders when the mother takes antiseizure medications during pregnancy. This has resulted in the European Medicines Agency changing its information on the risks of using antiseizure drugs during pregnancy. This new study provides additional evidence that specific types of antiseizure medication used during pregnancy can result in lower birthweight in relation to gestational age at birth.

“Smaller studies have reported that newborns exposed to specific antiseizure medications have low birthweight. This has been shown for topiramate, which also causes adults to lose weight. But the risk for other antiseizure medications has been limited or uncertain,” says Jakob Christensen.

This was the background for the new comprehensive Nordic study involving researchers and doctors specialising in epilepsy from Denmark, Finland, Iceland, Norway and Sweden. They linked the birthweight and length of pregnancy for 4,494,918 children – including 38,714 children of mothers with epilepsy – with information on these mothers’ use of antiseizure medication during pregnancy.

“The study is the largest of its kind. Children of mothers taking carbamazepine, oxcarbazepine, clonazepam or topiramate had a higher risk of low birthweight in relation to gestational age at birth, and carbamazepine was also associated with the risk of the newborn having a smaller head circumference,” adds Jakob Christensen.

Risk increases later in life

Topiramate has previously been associated with an increased risk of neurodevelopmental disorders among children, which has led to warnings from the European Medicines Agency that pregnant women and women planning to become pregnant should not take topiramate.

“Carbamazepine and oxcarbazepine have previously been standard treatments, but this study raises concerns about their use, since the use in pregnancy was associated with low birthweight. Why these drugs are associated with low birthweight remains unclear,” explains co-author Julie Werenberg Dreier, Senior Researcher, National Centre for Register-based Research, Aarhus BSS, Aarhus University, Denmark.

Restricted fetal growth during pregnancy has been linked to complications at birth but is also associated with other health risks. For example, low birthweight has been associated with an increased risk of diseases later in life, including cardiovascular diseases.

“The great strength of the new study is that the results are representative of pregnant women across the Nordic countries and that we adjusted for potential confounders, including socioeconomic conditions and certain lifestyle-related factors, such as maternal smoking and weight,” she says.

Discussion needed

An important aspect of the study is its size, which enabled the researchers to investigate both new and rarely used types of antiseizure medications. The researchers did not find any risk of low birthweight among children born to mothers who had used other types of antiseizure medication, including lamotrigine, valproate and levetiracetam.

This also applied to nine other types of antiseizure medication, although very few mothers and children were exposed to these.

“For lamotrigine, which is widely used by pregnant women, we did not find any correlation with low birthweight or reduced head circumference. The same applies to levetiracetam, which is also widely used. People planning a pregnancy may consider switching to one of these medications, which we are now reasonably sure are not associated with major risks in pregnancy,” explains Jakob Christensen.

Although several of the common types of antiseizure medication were not associated with increased risk in the study, some women cannot switch to lamotrigine or levetiracetam, for example, because of side-effects. In some cases, where there may be other risks of low birthweight, the risk of low birthweight associated with specific types of antiseizure medication when used in pregnancy should be considered.

“Being aware of the risk of reduced fetal growth is important and should be discussed when you want to become pregnant, including whether anything extra can be done in connection with the pregnancy to ensure that the fetus grows properly – for example, focusing on other modifiable risk factors that can cause low birthweight, such as smoking,” concludes Jakob Christensen.

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