TeraEpi: Teratogenicity of anti-seizure medication: the roles of epigenetics and folic acid supplements
Many anti-seizure medications (ASMs) are known to be teratogenic, however, underlying mechanisms are not yet fully understood. Throug investigations of cord blood from children born of mothers with epilepsy in the MoBa cohort, the TeraEpi project aims to unravel these mechanisms. The long term aim is to make treatment of pregnant women with epilepsy safer for both mother and child.
Every day thousands of pregnant women worldwide are prescribed medications for which we do not have sufficient information on fetal safety. Pregnant women are not included in randomized clinical trials due to ethical considerations, and medications are being marketed without sufficient information on safety during pregnancy. Epilepsy is a prevalent chronic disease and affects one in 250 pregnant women. Most need daily treatment with at least one anti-seizure medication (ASM) to control seizures. Uncontrolled epilepsy in a pregnant woman is potentially life-threatening for both mother and the unborn child. However, the use of ASMs can be harmful for the fetus. Thus, the clinician is left with a dilemma when weighing risks against benefits for pregnant women and the unborn child.
Although this dilemma has been acknowledged for decades, the underlying mechanisms of the harmful effects of ASMs remain remarkably elusive. The aim of the TeraEpi project is to unravel these mechanisms. One hypothesis is that exposure of the fetus to ASMs leads to changes in epigenetic patterns, i.e., changes in the molecular mechanism for regulating gene expression. Epigenetics is considered a regulator of gene expression, orchestrating both timing and level of gene expression during normal fetal development. We will analyse epigenetic patterns in cord blood samples from the large Norwegian Mother, Father and Child cohort (MoBa). Specifically, we will compare epigenetic patterns in children exposed to ASMs during pregnancy with children who were not exposed. Moreover, we will also investigate the effect of maternal intake of folic acids supplements on epigenetic patterns and its potential preventive effects. Improved understanding of mechanisms of harmful effects of ASMs is a prerequisite for improved follow-up of pregnant women with epilepsy, and for implementation of effective protective measures in the future.
The Regional Committees for Medical and Health Research Ethics (REC). REK-nr: 239237.
Project owner/ Project manager
Oslo Universitetssykehus HF