Global Perspectives
| Review Articles | |
| MANAGEMENT OF WOMEN WITH EPILEPSY -Compiled by Dr (Mrs) C Usha |
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3) Teratogenesis
Seizures during pregnancy have not been linked to malformations in the fetus. The maternal trait of epilepsy and use of AEDs have. Teratogenesis in infants of WWE could range from major congenital defects (such as neural tube and congenital heart defects) to minor anomalies (distal digital aplasia, hypertelorism, epicanthal folds, low hairline etc) [1][2][3]. All these findings have been consistent in several studies ranging over the last 25 years. Also, there was a tendency for developmental delay in infants of WWE as compared to controls. The conventional AEDs such as phenytoin, carbamazepine, valproate and phenobarbital are all teratogenic. Among the newer ones, with the exception of topiramate (which produced limb agenesis in rodents), all the others are rather safe – these have yet to be proved conclusively though [1]. Also, it must be borne in mind that teratogenecity increases with polytherapy [3]. A large dose of a single agent too may prove teratogenic – splitting it into multiple smaller doses can reduce this risk. The proposed mechanism of production of AEDs are reductions in folic acid leading to neural tube defects and production of free radical metabolites of AEDs. These free radicals can disrupt cell functions and structure leading to developmental defects [1][2]. Vitamin K AEDs that induce cytochrome P 450 appear to be associated with vitamin K deficiency in the newborn. This can result in coagulation disorders that can lead to life threatening bleeding disorders in the newborn. Maternal vitamin K supplementation can reduce the level of PIVKA (a protein induced by vitamin K absence). Thus vitamin K supplementation in the mother in the last month of gestation is important [1] [2]. 4) Breast feeding in WWE There are no absolute contraindications for breast feeding of infants born to WWE. In fact, a decision to breast feed should be encouraged after adequate counseling to the mother. AEDs are known to appear in breast milk in an inverse relation to the amount of drug that is protein bound. In infants, impaired hepatic clearance and protein binding may result in serum levels comparable to therapeutic levels. This may result in infant sedation and feeding difficulties (penobarbital and primidone). Rare hematologic consequences such as methemoglobinemia (phenytoin) and thrombocytopenic purpura (valproate) may also occur[1][2]. The long term growth and development of breast fed infants of WWE taking AEDs have not been studied. Management issues during menopause It is uncertain if the age of menopause is altered in WWE and those on AEDs. There is a paucity of data regarding this issue – however, it has been postulated that seizures and AEDs lead to premature ageing of the hypothalamo-pituiatry axis [1] [2]. What is known is that seizure frequency may be aggravated during this time and the woman should be made aware of this possibility. More studies are required to address this issue. WWE are also at an increased risk of metabolic bone disorders such as osteomalacia, osteoporosis and fractures. Theories of pathogenesis include increased metabolism of vitamin D to inactive metabolites by AED induced hepatic enzymes, AED interference with vitamin D absorption and a direct effect of AEDs on bone cell function. Conclusion Available data can be used to formulate guidelines – however, there are a lot of issues that have to be addressed conclusively. These patients should enjoy optimal control of seizures along with minimal risks to their overall health. Physician education surrounding management issues for WWE is required at all levels of training and practice. References
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