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Epilepsy Management during Pregnancy – Prevention of Birth Defects
Pregnancy Effect on Seizures – Seizure Effects on the Fetus – Epilepsy and Birth Defects – Risk of Mental Development Deficiency
Epilepsy Management during Pregnancy
Treatment of epilepsy during pregnancy is a double edged sword – epilepsy control vs. potential harm to the fetus. Whenever possible, pregnancy in epilepsy has to be planned.
Medication change, initiation, and discontinuation during pregnancy have to be avoided. Epilepsy treatment plan has to be in place before conception. Dramatic physiological changes during pregnancy alter often change the seizure pattern and drug effectiveness.
In the ideal world, there should be no drugs during pregnancy. In reality, it all depends on the type and severity of seizures. Generalized violent seizures have to be controlled because they put both mother and fetus in danger. Treatment in other types of seizures could be less aggressive.
Pregnancy Effect on Seizures
An epilepsy response to pregnancy is variable. The majority experiences no change, about a quarter have increased seizures and around 15% have a reduction of seizure frequency.
Physiological changes during pregnancy, such as change in sex hormone levels, activation of kidney and liver functions, and increased body volume – make anti-epileptic drugs less efficient.
Blood levels of some medication drop as much as 60% (Phenytoin and Levetiracetam). The doses have to be adjusted accordingly. For the same reason doses have to be tapered down after delivery in order to avoid toxicity.
Seizure Effects on the Fetus
Whether seizures may cause birth defects, remains surrounded by controversies. There is no proof that seizures in the first trimester may cause any birth defects.
The major concern remains that fall during seizures may cause a direct damage to the uterus leading to bleeding, premature labor, and fetal death.
Seizures during labor occur in about 5% of women with epilepsy. There is no evidence that those seizures increase the risk of complications.
The reason for epilepsy treatment in pregnant women remains the same as for non-pregnant ones – giving ability to work, drive, avoiding injuries and status epilepticus (persistent life threatening seizures).
Epilepsy and Birth Defects
Babies born to mothers with epilepsy are at increased risk of major birth defects and minor abnormalities. This sub-chapter will address the major causes of the birth defects in children born to mothers with epilepsy.
The first trimester is the most critical for the normal organ development. Insult at a certain time leads to the damage of a particular organ that is being formed at the moment: neural tube defects (brain, spinal cord) day 28, cleft lip day 36, heart septal defect (wall between right and left chambers) day 42, cleft palate days 47-70.
Women with epilepsy who are not receiving anti-epileptic medications do not have increased rate of major birth defects. Babies born to mothers on anti-epileptic medications during pregnancy have the rate of minor and major birth defects 2 to 3 times of the general population. Not all drugs are the same.
Valproate is the worst in this sense, followed by Phenobarbital (5.5%) > Topiramate (4.2%) > Clonazepam (3.2%) > Carbamazepine (3%) > Phenytoin (3%) >Levetiracetam (2.5%) > Oxcarbazepine (2.2%) > Lamotrigine (2%) > Gabapentin (0.5%) > Zonisamide (?).
Valproate carries 6% to 9% chance of birth defects. The most common are spina bifida and other neural tube defects.
Topiramate more often causes cleft palate and lip.
Phenobarbital is more likely to cause heart defects.
Combination of multiple drugs in many cases increases the rate of complications.
In some (but not all) medications, birth defect rate might depend on the dose. For Carbamazepine it is 2% with less than 400 mg per day and 7.7% for doses above 1000 mg per day. Lamotrigine – 1.7% for less than 300 mg per day and 3.6% for higher doses.
Risk of Mental Development Deficiency
Studies prove that the risk of mental deficiency in children of women with epilepsy is real and it is drug related. Cognition is not reduced in children of untreated women with epilepsy.
Valproate is the worst again. Phenytoin, Phenobarbital, and multiple drugs also claim their toll on mental development.
In one study, Valproate is shown to increase autism spectrum disorders almost 10 times that of general population.
Folic acid supplementation during pregnancy appears to lessen negative anti-epileptic drug effect on the brain.
Prevention of Birth Defects in Epilepsy
An individual approach to seizure treatment during pregnancy is a key point for successful outcome. Each patient has an individual pattern, triggers, severity, and types of seizures.
Switching to more fetus friendly medication has to be done prior to conception.
Multiple drugs have to be avoided whenever possible.
Occasional mild epilepsy that is not treated otherwise does not have to be treated during pregnancy either.
Folic acid supplementation during pregnancy is a must (unless contraindicated).
Abrupt withdrawal from anti-epileptic drugs prior to or during pregnancy is not a good idea. It can cause a life threatening status epilepticus which puts the mother and the baby in great danger.
Changing medications during pregnancy has to be avoided.