Researchers have made progress towards a genetic test aimed at enabling mothers with epilepsy to safely take valproic acid (VPA) medication without the risk of causing birth defects in their children.
Valproic Acid and Pregnancy Risks
Valproic acid is an anti-seizure medication that serves as the primary or most effective treatment for many individuals with epilepsy. However, its use is increasingly restricted in several countries. This is due to approximately a 10 percent risk of structural birth defects in babies born to mothers taking VPA during pregnancy. These defects can range from severe neural tube defects to milder conditions like cleft palate.
Research Findings
The study, published in the academic journal Neurology, was led by Monash University in collaboration with Australian and international researchers, and the Raoul Wallenberg Australian Pregnancy Register.
It identified specific DNA sequence variations in mothers that can alter the risk of their child being affected by VPA during pregnancy. The research found that VPA influences the function of molecules that bind to DNA and regulate gene activity during fetal development. Genetic variants within a mother’s DNA can impact this binding process, which helps explain why the drug only elevates the risk of adverse effects in some fetuses.
Towards a Genetic Test
Dr. Alison Anderson, lead researcher and a bioinformatician at Monash’s School of Translational Medicine, stated that the team is developing a genetic test.
This test aims to identify individuals who could safely take VPA during pregnancy because they do not carry the genetic risk for birth defects.
Dr. Anderson emphasized the importance of solving this problem. Clinicians must balance the risks to infants from VPA exposure against the mother's risk of injury or death from uncontrolled seizures if they discontinue or switch to less effective medication. For some women, VPA is the only effective seizure control medication.
The goal is to ensure that individuals without the genetic risk for VPA-related birth defects can continue their treatment.
Importance of Registries and Future Steps
Professor Terence O’Brien, a senior researcher and neurologist at Monash School of Translational Medicine, highlighted the critical role of pregnancy registries in providing data for this research. These registries offer insights into how pregnant women with epilepsy and their babies fare with and without medication.
This information is considered crucial for advancing towards precision medicine, allowing for the prediction of medication responses based on a patient’s genetic makeup rather than relying on trial and error.
A related study by the same Monash University group, published in Neurology in November, utilized deep learning models to integrate genomic and clinical data to predict responses to first-line treatments in newly diagnosed epilepsy patients. The next phase of this research will involve using advanced deep learning tools to predict the effects of genetic variants on drug therapy and adverse effects, supported by the activation of the University’s MAVERIC supercomputer this year.