"In a Revolution"

Epilepsy in Pregnant Women

In Medical Sciences on May 8, 2011 at 6:55 pm

 In this article I have created a special package for Mr. Felix Xia, who gave positive feedbacks on my previous article and I had promised to write a special article on epilepsy in pregnant women.

I will continue the discussion about epilepsy, but this time related to pregnant women. What are the effects on pregnant women? How about the managements? Let me share here about it all!


The Epilepsy Effect vs Epilepsy Therapy Effect on Pregnancy

According to United States statistics, 0,5% of pregnancy observed in women with epilepsy. Risk in women with epilepsy who become pregnant is higher than normal women who are pregnant. Neonatal mortality rate in patients with epilepsy who become pregnant are three times higher than normal population. Meanwhile, nearly 12000 of women in the United States become pregnant during treatment with Anti Epileptic Drugs (AED). About 6% of infants born to mothers who received therapy AED yamg suffer birth defects anatomically and physiologically.

The influences of pregnancy on epilepsy have a variation. About ¼ of cases will increase the frequency of seizures, especially in the last trimester. About ¼ will decrease and ½ doesn’t change during pregnancy. Why does it happen?

In pregnant women physiological changes occur in their bodies. One is the marked increase in kidney function with creatinine clearance increased by approximately 50%, so will reduce the level of Anti-Epilepsy Drug (AED) in the blood circulation which in turn will increase the demand AED. Besides that, the estrogen hormone is epileptogenik. These hormones continue to rise during pregnancy and reach its peak in the third trimester. These are what cause the seizures frequency of epilepsy increase especially in the last trimester.

Then, what is the impact on pregnancy? The seizures during pregnancy increase the risk of adverse pregnancy outcomes. Seizure in the first trimester is known to increase risk of birth defects in offspring 12.3% vs. 4% with children who are exposed seizures of mother in other time. Generalized tonic-clonic increases risk of hypoxia and acidosis, as well as damage from blunt trauma. Researchers from Canada found that the maternal seizures during pregnancy may increase risk of developmental disorders. It is rare, status epilepticus can cause high levels of mortalias for the mother and the child. In a study of 29 cases reported, 9 women and 14 children died during or shortly after the episode of status epilepticus. A child of a woman who has three times the generalized tonic clonic seizures during pregnancy can cause intracerebral hemorrhage.

            What are the impacts of the anti-epilepsy drug in pregnant women? The impact of the most common in pregnant women with epilepsy is the potential for AED teratogenesis. Teratogenic effects were classified as major malformations or minor anomalies and both are associated with the use of AED. A major abnormality is an abnormality present at birth that may require surgical treatment. Major malformations that may be congenital heart defects, urogenital abnormalities, neural tube defects, and cleft. Minor anomalies such as facial dysmorfism and finger anomalies.

        However, according to the American Academy of Neurology in 2009, it was said that consuming AED does not cause difficulties during pregnancy. Thus there is strong evidence that AED is not a high risk for bleeding during pregnancy. It also said the risk of preterm labor and Caesar delivery is not high enough. Not enough evidence to suggest that the AED was associated with increased blood pressure in pregnancy. However, please be careful if you can not avoid more than one AED during pregnancy! There are some evidences to suggest that the use of multidrug valproic acid can cause birth defects thus forbidden to consume valproic acid, especially in the first trimester.

How About The Treatment of Epilepsy in Pregnant Women?

            Once pregnant, a woman with epilepsy who consumed AED should be followed by obstetricians. A high-risk obstetrician or maternal fetal specialist selected although not always possible. Pregnant women should be checked serologically and the ultrasound in the first trimester to determine the risk of neural tube defects.

        AED level monitoring throughout pregnancy will help to control seizures. AED pharmacokinetics influenced physiological changes of pregnancy. During pregnancy, renal blood flow and glomerular filtration will increase as a function of increased cardiac output and plasma volume, extravascular fluid and increased fatty tissue to create a larger volume of distribution. Decrease in serum albumin levels, which reduce drug binding, increasing the free fraction, and increasing drug clearance. Pharmacokinetics may affect the concentration of AED and the most important for AED is highly protein binding, metabolized in the liver  or renal clearance. AED with high-protein bond in the amount of total and free, including for phenytoin and valproic should be monitored.

        Vitamin K prophylaxis is recommended during the last weeks of pregnancy, starting around week 36. Incidence of haemorragic in newborns reportedly increased in children exposed AED during pregnancy, which stimulates the cytochrome P450 enzyme system. AED which stimulates the enzyme cytochrome P450, include phenobarbital, primidon, phenytoin, carbamazepine stimulate fetal microsomes enzymes that degrade vitamin K.

        American Academy of Neurology and American Academy of Pediatrics to allow women with epilepsy who consume the AED to breastfeed. During breastfeeding, however, the baby will also be affected by AED at a certain concentration. If the mother that receive ethosuximid, phenobarbital, or pirimidon choose to breastfeed, they must be trained to monitor the children looking for signs of sedation and lethargy. In case reports, phenytoin, carbamazepine, and valproic probably safe. These AED are not transferred to the child through breast milk at the same concentration in the mother.


          Now a woman who has epilepsy no longer prohibited for pregnant women and delivery babies. Not taking anti-epileptic drugs is not a good solution, because if the mother experienced seizures during pregnancy also affects for the fetus. Therefore, the necessary cooperation from the patient for routine birth control to see the development of the fetus due to anti-epilepsy drug that is consumed.

Written by CatherineManame Uli

The References

  1. Manajemen Epilepsi pada Kehamilan. Available from the URL: http://journal.uii.ac.id/index.php/JKKI/article/viewFile/547/471
  2. Clinical Management of Pregnant Women with Epilepsy.  Available from the URL : http://www.medscape.com/viewarticle/530483
  3. Women with Epilepsy: Drug Risks and Safety during Pregnancy. Available from the URL : http://www.aan.com/practice/guideline/uploads/338.pdf

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