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Epilepsy in Pregnant Woman

Introduction

With prevalence rate of about 0.5% epilepsy is found to be one of the most comman neurological disorder in pregnant women. In India alone a total of over 2.5 million woman suffer epilepsy and about half of the incidence occurs among women in the irreproductive age. However, most women with epilepsy during pregnancy are not adequately informed about their optimal management.

According to researchers, pregnancy influences natural history of epilepsy, which is worse in about one-
third of women. Since most antiepileptic drugs (AEDs) are potentially teratogenic, there may be an increase the risk of fetal malformations. The main aim of anticonvulsant treatment in women with pregnancy is to gain the best possible control of seizures with least adverse effects on the foetus.

Several mechanisms, including syndromes such as metabolic derangement, eclampsia, and cerebral venous sinus thrombosis, can induce seizures during pregnancy and postpartum period, epilepsy being the commonest amongst them. Majority of women with have seizures before pregnancy. However, some women may experience seizures only during pregnancy, which is termed gestational epilepsy. Approximately 1 % - 2% of women with epilepsy may experience status epilepticus (SE) during pregnancy, which is associated with high morbidity and mortality.

Effects of hormones on epilepsy
Clinical date indicates that seizures are influenced by the sex hormones such as estrogen and progesterone: Estrogen is found to lower seizure threshold and progesterone elevates it. The threshold for seizures is lowered by the induced by electroshock, kindling, pentylenetetrazol and other agents. Progesterone, on the other hand, reduces spontaneous and induced epileptiform discharges.

Pregnancy and frequency of seizure
Seizure frequency may remain unchanged or decrease in two-third of pregnant women with epilepsy, whereas it may increase in others. These women may have a stable or unstable pattern seizure frequency throughout the pregnancy. According to researchers, about 61% patients have a stable pattern and 39% had an unstable pattern. Several other factors such as noncompliance and decrease in blood levels of free form of AED, may also influence seizures during pregnancy (Table 1).

Epilepsy management during pregnancy
Pregnancy management in women with epilepsy is a critical challenge as seizures may have harmful effect on the fetus. In the first trimester and during the delivery period, the risk of seizures is highest. Conventional AEDs can be effectively use in pregnancy. However, all of the conventional AEDs are associated with an increased risk teratogenicity in the newborn and are categorized as US Food and Drug Administration class C or D. Multiple studies have shown that, therapy with these three drugs carries the highest risk.

The main aim of the anticonvulsants treatment in women with pregnancy is to gain the best possible control of seizures with least adverse effects on both the mother and offspring. Treatment with monotherapy should be achieved, if possible.19 In this regards, recent studies suggest that the newer AEDs given as monotherapy may have a lower teratogenic risk.

The newer AEDs that are devoid of hepatic enzyme induction such as gabapentin, lamotrigine, and levetiracetam, do not appear to significantly alter gonadal hormones. These drugs may be less teratogenic to humans than conventional AEDs, although orofacial clefts have recently been reported.

Recommendations:
It has been observed that the risks can be minimized by the preconceptual use of multivitamins with folate, by using AEDs in monotherapy at the lowest effective dose, and by preventing maternal seizures .

Dose adjustment is made on a clinical basis. Plasma AED concentrations will fall in all pregnant women, but only one-fourth to one-third of pregnant women will have an increase in seizures.

Vitamin supplementation: Folate (0.4 mg/day) is recommended by for all women of childbearing age, whether or not they have epilepsy. Reduction in the risk of malformations in general, and of neural tube defects (NTDs) in particular, in women taking folate prior to conception has been observed.

Conclusion
Women with epilepsy should be given special care as they can have several special problems related to pregnancy. However, it is comforting to know that majority of women with epilepsy can have safe pregnancy and childbirth. Teratogenic effects are attributed to exposure to AEDs, which seems to occur in a small proportion of women. An appropriate preconception management and choice of AEDs can reduce the risk.

     
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