Epilepsy is a common neurological condition characterized by recurrent seizures. It is common for women of childbearing age to require continued drug treatment during pregnancy in order to prevent seizures that could be dangerous to both themselves and their unborn child. It is however believed that these drugs may adversely affect the normal development of the fetus. Some drugs have been demonstrated to be teratogenic (the ability to cause birth defects) such as Daflapt, Phenobarbital, and Tegretol, however, there are relatively few studies examining the effects of anticonvulsant therapy during pregnancy on neurocognitive development, ADHD, and autism risk among children, especially with relatively new drugs such as Lamictal and Topamax.
Tompax and Deflate – the known and what has yet to be discovered
Studies indicate that exposure to Depalept during pregnancy, even at low doses, significantly increases the risk of a wide variety of congenital disorders, such as heart defects and spina bifida. Moreover, Depalept was associated with a decrease in the intellectual and cognitive function of these children, and an over two times greater risk of developing autism and attention deficit disorders. Due to these concerning data, the use of Depalept in women of childbearing potential is restricted to exceptional and particularly severe cases only.
Topamax is a drug known to somewhat increase the risk of cleft lip in infants who were exposed to it during the first half of pregnancy. However, there is still little information about the effects of Topamax on fetal neurological development. While a large Nordic study published in July 2022 indicated the risk of autism among infants exposed to Topamax during pregnancy increased by 2.8 times, these data were preliminary, and the exact scope of exposure to the drug, particularly during the second and third trimester of pregnancy, was unclear.
What is behind the increase in risk?
To thoroughly examine the relationship between treatment with Topamax, Depalept and Lamictal (a relatively safe antiepileptic drug) during pregnancy and the risk of autism, a new and broad-scope study was conducted in the US, including data on over 4 million births and an 8-year follow-up of the children born to women who took said drugs during the second half of their pregnancies.
Researchers found that among mothers with epilepsy, compared to mothers who had never been treated with anti-epileptic drugs, the risk of autism increased by 2.7 times in children exposed to Depalept, consistent with previous findings. However, no significant difference in the risk of autism was found among children exposed to Lamictal or Topamax during pregnancy. Moreover, for Topamax, no increased risk of autism was observed in separate analyses of infants who were exposed to high or low doses of the drug, or who were only exposed to the drug during the first half of the pregnancy, while taking into account important intervening variables such as a background of mental illnesses and other neurologic disorders in the mother. The percentage of autism observed in children of mothers who took Lamictal or Topamax without this type of background was found to be even lower.
Researchers speculate in this study that part of the increase in the risk of autism among children of mothers treated with anticonvulsants is not a result of the drugs themselves – but rather, they are a result of common genetic mechanisms between epilepsy and the tendency for developing autism, or a result of the effects of the illness and seizures during pregnancy on child development. However, it appears that Depalept specifically impairs the proper development of fetal brain tissue by a different mechanism – apparently, through direct toxicity during the synapse-formation period in the fetal brain, starting in the second half of pregnancy. The damage to the structure and function of the brain apparently underlies the substantial cognitive and behavioral impairment observed in children exposed to the drug, even many years after their birth.
Use of antiepileptic drugs responsibly and carefully
Despite the initial excitement around these encouraging and reassuring results regarding Topamax, it is important to remember that available information is still limited, and that further study is required to establish the fetal safety of the drug during pregnancy. Additionally, one should remember that Topamax was associated with other fetal risks, such as low birth weight and cleft lip. Lamictal, which is considered to be the safest drug to use during pregnancy, may also have mild effects on infant weight and growth.
The decision to start or continue antiepileptic treatment during pregnancy must be made after a discussion between the patient and the attending physician.
The pros and cons of each drug must be carefully weighed, and the known and unknown risks to the fetus must be taken into account. This, while understanding that uncontrolled and untreated convulsions during pregnancy are a real and proven danger to the health of the mother and the fetus, and therefore the most suitable treatment for the patient must be found.
In conclusion, while this topic requires further consideration and research, it is important that doctors, genetic counselors and women with epilepsy who are planning a pregnancy know the various risks of the existing medications, in order to be able to make an informed decision and choose the most balanced, optimal and safest treatment for them and their future children.
