Summary: A new study from Aarhus University indicates that certain types of epilepsy medication taken during pregnancy may increase the risk of severe psychiatric disorders in children.
The research found a worrying link between the antiseizure medication valproate and the child’s risk of developing psychiatric disorders such as autism, ADHD and intellectual disability.
The study underscores the need for more research to help pregnant women with epilepsy and their doctors make informed decisions about the use of medicine during pregnancy.
- Children born to mothers who took epilepsy medication during pregnancy have a higher risk of developing severe psychiatric disorders, according to a study by Aarhus University.
- The study found a link between the antiseizure medication valproate and an increased risk of diseases such as autism, ADHD, and intellectual disability.
- The research underscores the need for more accurate risk estimates and further investigation to help pregnant women with epilepsy and their doctors make informed decisions about the use of medicine during pregnancy.
Source: Aarhus University
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.
The research is published in the journal JAMA Neurology.
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 percent of children of mothers who used valproat during pregnancy developed a psychiatric disorder before the age of 18. By comparison, only 31 percent 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 emphasizes 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.
About this neurodevelopment research news
Original Research: Closed access.
“Prenatal Exposure to Antiseizure Medication and Incidence of Childhood- and Adolescence-Onset Psychiatric Disorders” by Julie Werenberg Dreier et al. JAMA Neurology
Prenatal Exposure to Antiseizure Medication and Incidence of Childhood- and Adolescence-Onset Psychiatric Disorders
Prenatal antiseizure medication (ASM) exposure has been associated with adverse early neurodevelopment, but associations with a wider range of psychiatric end points have not been studied.
To examine the association between prenatal exposure to ASM with a spectrum of psychiatric disorders in childhood and adolescence in children of mothers with epilepsy.
Design, Setting, and Participants
This prospective, population-based register study assessed 4 546 605 singleton children born alive in Denmark, Finland, Iceland, Norway, and Sweden from January 1, 1996, to December 31, 2017. Of the 4 546 605 children, 54 953 with chromosomal disorders or uncertain birth characteristics were excluded, and 38 661 children of mothers with epilepsy were identified. Data analysis was performed from August 2021 to January 2023.
Prenatal exposure to ASM was defined as maternal prescription fills from 30 days before the first day of the last menstrual period until birth.
Main Outcomes and Measures
The main outcome measure was diagnosis of psychiatric disorders (a combined end point and 13 individual disorders). Estimated adjusted hazard ratios (aHRs) using Cox proportional hazards regression and cumulative incidences with 95% CIs are reported.
Among the 38 661 children of mothers with epilepsy (16 458 [42.6%] exposed to ASM; 19 582 [51.3%] male; mean [SD] age at the end of study, 7.5 [4.6] years), prenatal valproate exposure was associated with an increased risk of the combined psychiatric end point (aHR, 1.80 [95% CI, 1.60-2.03]; cumulative risk at 18 years in ASM-exposed children, 42.1% [95% CI, 38.2%-45.8%]; cumulative risk at 18 years in unexposed children, 31.3% [95% CI, 28.9%-33.6%]), which was driven mainly by disorders within the neurodevelopmental spectrum. Prenatal exposure to lamotrigine, carbamazepine, and oxcarbazepine was not associated with an increased risk of psychiatric disorders, whereas associations were found for prenatal exposure to topiramate with attention-deficit/hyperactivity disorder (aHR, 2.38; 95% CI, 1.40-4.06) and exposure to levetiracetam with anxiety (aHR, 2.17; 95% CI, 1.26-3.72) and attention-deficit/hyperactivity disorder (aHR, 1.78; 95% CI, 1.03-3.07).
Conclusions and Relevance
Findings from this explorative study strengthen the evidence for the warning against the use of valproate in pregnancy and raise concern of risks of specific psychiatric disorders associated with topiramate and levetiracetam. This study provides reassuring evidence that lamotrigine, carbamazepine, and oxcarbazepine are not associated with long-term behavioral or developmental disorders but cannot rule out risks with higher doses.