Effect of Maternal Epilepsy (Seizure) Over Children and Safety of Drug During Pregnancy

Effect of Maternal Epilepsy (Seizure) Over Children and Safety of Drug During

Pregnancy may affect a patient's epilepsy, the patient's epilepsy may affect the developing fetus, and antiepileptic drugs (AEDs) may affect the developing fetus. Although there are many aspects of importance regarding pregnancy and epilepsy, such as fertility, the biological and social consequences of epilepsy, the impact of the underlying etiology of the epilepsy, genetic factors, etc.


If you have epilepsy and you're considering becoming pregnant, talk to your doctor. Most women with epilepsy can become pregnant and have a healthy baby, but many need to adjust their medications and be carefully monitored throughout pregnancy. It is very important to work with your doctor and to plan your pregnancy.Abruptly stopping your medication during pregnancy is a very bad idea.

Study shows that most antiepileptic drug regimens were associated with an increased risk of major congenital abnormalities in the offspring, in particular valproate (dose-response relationship) and carbamazepine monotherapy, benzodiazepines in polytherapy, and caffeine comedication in combinations with Phenobarbital. Some medications for epilepsy, like Depakote, Depakene, and phenobarbital, may increase the risk of birth defects. The safety of some other medicines in pregnant women hasn't been proven.

A study concluded that the absolute excess in the prevalence of major malformations was 26/1000 births in the offspring of mothers with epilepsy in relation to the offspring of reference mothers. The highest relative risk was observed in spina bifida and congenital anomalies of genital organs. However, these malformations cover only a small proportion of all major malformations.

Recently the FDA issued an alert concerning Lamictal. The Agency noted that women taking the drug during the first three months of pregnancy have a higher chance of giving birth to a child with a cleft lip or cleft palate. Unfortunately, there is no medication that has been proven safe for the developing fetus. Changing or reducing the antiepileptic medication prior to pregnancy may be advised. As children grow up and their body weight increases, their dose may need to be increased. A larger dose may also be advised if seizures are not fully controlled, and also sometimes in late pregnancy.

It is recommended that the ideal AED concentration should be established for each patient before conception and that monitoring of AED concentrations should be performed during each trimester and in the last month of pregnancy. The ideal management of women with epilepsy during pregnancy and the postpartum period involves achieving an optimal balance between minimizing fetal and neonatal exposure to the deleterious influences both of antiepileptic drugs (AEDs) and of seizures.

A 2001 study reported greater mental flexibility and memory capacity in some children with a history of febrile seizures compared to peers who did not have these seizures. A 2000 study suggested, however, that it may affect long-term memory. Patients with seizures originating on the left side of the brain may also have less well-developed language skills than those with right-side epilepsy.

WHO recommends phenobarbital as the treatment of choice in resource restricted countries, but this policy has been questioned because of concerns about adverse behavioral effects, particularly in children. However, a study of children in Bangladesh also published in BMJ, found no significant difference in behavioral problems between phenobarbital and another drug called carbamazepine. Despite some limitations, the study provides more evidence to support the use of phenobarbital in developing countries.

Children with seizures that are not well-controlled are at higher risk for intellectual decline. Another study shown that girls with severe epilepsy had the highest rate of behavioral problems (and they worsened over time) compared to boys and girls with mild or moderate epilepsy and all children with asthma, another chronic illness. They were slightly more likely to be unemployed, unmarried, and childless compared to the general population.

Children of women who took the epilepsy drug valproate during pregnancy appear to be at a greater risk for lower IQ, according to recent research. The study looked at IQ test results for 187 two-year-old children of mothers who took the epilepsy drugs carbamazepine, lamotrigine, phenytoin, or valproate during pregnancy. Children with higher levels of valproate in their blood had lower IQ scores.

Men born to mothers with epilepsy may suffer adverse effects on their intellect that can be seen nearly 20 years later, according to the findings of a new study.

Having a mother with epilepsy and who is receiving treatment for epilepsy may be an early-life factor that has adverse effects on the intelligence in adulthood, Dr. Nina Oyen, of Statens Serum Institute, Copenhagen, Denmark, state. However, the majority of studies on intelligence and fetal exposure to antiepileptic drugs have focused on children younger than 5 years old.

The researchers therefore examined the adult intellectual performance and height in men born to mothers with epilepsy and compared then to those with mothers without epilepsy.

The team linked information on maternal epilepsy reported to the Medical Birth Registry of Norway from 1967 to 1979 with information on 18- to 19-year-old men's IQ scores and body measurements reported in the Norwegian Conscripts Service from 1984 to 1999. The results are reported in the medical journal Epilepsia.

The authors found that the average IQ score on a scale of 1 to 9 - reported by the draft board - was lower in the 1207 conscripts whose mothers had epilepsy compared with the 316,554 conscripts of mothers who did not have the disease, with average scores of 4.8 versus 5.2, respectively. When the researchers took into account the influence of the mother's educational level, the mother's age, birth order, marital status, year of birth, and weight and length at birth did not change the difference in IQ scores.

When the two groups of men were compared, those with epileptic mothers were 60 percent more likely to have a lower IQ score.
The average height of the conscripts with epileptic mothers was also significantly lower, at 178.6 centimeters compared with 179.9 centimeters.

These results illustrate the need for population-based registries with complete long-term information on of infants exposed prenatally to epileptic drugs, such as phenobarbital and phenytoin, which are still widely used in many countries, as well as exposure to newer drugs to control seizures, Oyen and colleagues conclude. "It remains to be seen whether the newer antiepileptic drugs are safer to offspring exposed during fetal life."

Women with epilepsy who have taken the drug valproic acid to control seizures may have an increased risk of having a baby with spina bifida. The malformation pattern associated with phenobarbital is similar to that seen with phenytoin. Carbamazepine was thought to be the safest of the antiepileptic drugs, but recently it too has been associated with spina bifida at a rate of approximately 1%.

The new neurons generated as a result of neural damage due to epilepsy show a reduced excitability that could alleviate the disorder. The researchers suggest that therapies for epilepsy aimed at inducing neurogenesis could prove effective in alleviating the disorder.

While the general consensus is that use of antiepileptic drugs is associated with increased risk for birth defects, physicians weigh this risk against that of uncontrolled epileptic seizures, which can be more harmful to the fetus than the actual drugs. Most women with active epilepsy choose to continue with drug therapy during pregnancy and have more than 90% chance to give birth to a perfectly healthy child. It remains unsolved whether risks for birth defects vary with different drugs.

Another study suggested that a distinctive pattern of physical abnormalities in infants of mothers with epilepsy is associated with the use of anticonvulsant drugs during pregnancy, rather than with epilepsy itself. In most women treated for epilepsy, seizures remain well controlled during pregnancy; such women have uneventful pregnancies and deliver healthy babies.

During pregnancy, metabolic and excretory processes change, however, so that the plasma concentrations of some antiepileptic drugs, particularly phenytoin, can fall. It is important to be alert to this possibility, and pregnant women with epilepsy should therefore be seen more often than those without epilepsy.

Use of the anticonvulsant drug valproate during pregnancy may pose a significantly great risk of birth defects than does use of other anti seizure medications. Massachusetts General Hospital (MGH) reports that the basic message for women who take valproate is to plan ahead if they want to have children. Discuss the risks with their physician and consider taking alternative drugs.

The management of a pregnant woman with epilepsy should start during the pre-pregnancy period. Experts recommended that the physician optimize control of seizures with the lowest possible dose of a single agent; give folic acid supplementation; and counsel the patient about risks. In the prenatal period, serum anticonvulsant levels should be regularly checked to adjust the dose to control seizures. The fetus should also be regularly checked. Finally, during delivery and the postpartum period, the physician should strive to avoid occurrences of convulsions.

A small device implanted in the skull that detects oncoming seizures, then delivers a brief electrical stimulus to the brain to stop them is under study at the Medical College of Georgia. Researchers at MIT are developing a device that could detect and prevent epileptic seizures before they become debilitating.

The similarity between the children exposed prenatally to carbamazepine and those with the fetal hydantoin syndrome is probably related to the fact that both drugs are metabolized through the arene oxide pathway and raises the possibility that it is the epoxide intermediate rather than the specific drug itself that is the teratogenic agent; another study suggested.

Scientists have uncovered that a single gene mutation prevents a specific ion channel from functioning correctly, thus causing excitability which results in epilepsy. This discovery will be helping us to understand how and why this form of epilepsy, known as benign familial neonatal-infantile seizures, appears in these infants. This highlights the complexity of the human brain and how disorders can develop if one single mechanism goes away.

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