Epilepsy is a common chronic neurological disorder that affects people of all ages. It is caused by abnormal electrical activity in the brain. A person with epilepsy experiences a sudden episode of seizures, which may include sensory disturbance, unconsciousness, and repetitive muscle jerking (Wlodarczyk et al., 2012). The treatment is the daily intake of antiepileptic drugs (AEDs) regimen. More than 90% of pregnancies proceeds without complications in women with epilepsy, although there is the slight increase in adverse effect outcome that is found, it is advised that women with epilepsy should do careful planning of pregnancy, pregnancy counseling and delivery management (Viinikainen et al., 2006). Complications associated with epilepsy during pregnancy include prolonged labor, vaginal bleeding, surgical delivery, preeclampsia (which occurs in 5-6% of all pregnancies), and frequency of seizures (Viinikainen et al., 2006). There are many interactions between epilepsy and pregnancy, but the main concern is the effect of AEDs on the development of the fetus. The maternal is advised to take the AEDs treatment to prevent the detrimental effect of epileptic seizures on themselves and the fetus (Meador et al., 2008). The problem with outcome exposure of these AEDs is that they increase the risk of congenital malformation, fetal death, feeding difficulties, neonatal hemorrhage, low birth weight neurocognitive development, and childhood epilepsy on the child (Viinikainen et al., 2006), these effects make it difficult to manage epilepsy during pregnancy. What also needs to be considered is the risk that is linked with uncontrolled seizures on the maternal and the fetus, the effect of pregnancy on the controlled seizure, the potential development of toxicity of the epilepsy drugs treatment (Battino and Tomson, 2007). The aim of this literature review is to discuss the management of epilepsy during pregnancy with an emphasis on the teratogenic effect of antiepileptic drugs as well as the control of seizures during pregnancy, and the effect of pregnancy on the AEDs.
About 3.8% of women with epilepsy experience epileptic seizures free throughout their pregnancy period of all maternal deaths in the United Kingdom convulsion, this is greatly more than expected from the commonness of epilepsy in pregnancy (Battino and Tomson, 2007). Seizures may be detrimental, causing physical damages and sometimes lead to the death of the patient with epilepsy (Battino and Tomson, 2007). Seizures are not likely to contribute greatly to the increased risk of birth defects. Even though the total risk is low, but many studies have reported that a larger than expected number of maternal deaths in the United Kingdom is caused by epilepsy seizures. Most maternal stops taking their treatment as soon as they realize that they are pregnant. Mortality of maternal and fetus is partly related to the seizure occurrence after stopping AEDs treatments (Battino and Tomson, 2007). The fetus effect depends mainly on the type of seizure the maternal might be experiencing. For instance, some seizures might be harmless on both the maternal and the fetus while others are detrimental and might lead to death. There are convulsive seizures, this includes maternal falls that might lead to injury of both the maternal and the fetus or even abruptio placentae if there is blunt trauma to the abdomen. Most of the uncontrolled convulsive seizure leads miscarriages (There are many anecdotal and case reports of miscarriage following a generalized seizure), intracranial bleeding, and suppression of fetal heart rate (Tomson et al., 2013). While uncontrolled tonic-clonic seizures may have a less harmful effect on the fetus compared to convulsive seizures. But this is still potentially dangerous to the maternal and the fetal, although strict evidence is lacking, this is generally also assumed to be more harmful to the fetus than are antiepileptic drugs (Battino and Tomson, 2007). Even though the absolute risk is very low, it is important to have seizures control for maternal health.
“The physiologic changes that take place during pregnancy can affect any level of the disposition of the drugs from absorption, distribution, metabolism to excretion. Every pregnancy represents a singular occurrence of genetic variation and environmental factors, and AEDs may interact differently with any of these in the individual and, also differently from pregnancy to pregnancy’ (Wlodarczyk et al., 2012). Pregnancy can remarkably affect the pharmacokinetics of the AEDs with the potential consequences for seizure control as well as the drug exposure to the fetus (Tomson et al., 2013). Epilepsy and pregnancy studies have reported that the AEDs differ in their teratogenic potential, some AEDs are less harmful (carbamazepine, phenytoin, or lamotrigine) while others are dangerous (valproic acid) and they increase the risk of congenital malformation, also the harmful effect of these epileptic drugs on the fetus are dose-dependent (Meador et al., 2009). The dose-dependent tells us that the maternal and fetus susceptibility to the teratogenic effect of the AEDs with similar exposure in the type and dose of the drug as well as the normal genetic factors are likely to contribute to the major congenital malformation in children who are a mother is epileptic (Tomson et al., 2015). During pregnancy, the plasma volume progressively increases and affects the drug disposed of within the body. The total drug plasma concentration decline, and in some cases, this may lead to adverse seizure control. The storage of fat increases and the elimination of the fat-soluble drug becomes slow. The duration of fat-soluble accumulates in the system depends on the absorption and elimination of that drug within the system. It was observed that exposure to these drugs during pregnancy leads to cardiac malformation, hypospadias, and facial cleft (Wlodarczyk et al., 2012).
Women with epilepsy are more likely to have obstetrical complications during pregnancy than are women in the general population (Yerby, 1991). Pregnancy has multiple influences on the effect of seizure control in most epilepsy cases. Even though population-based studies stipulate that symptoms decline in 15-30% of women, they improve in a similar proportion of women. This could partly indicate random variation. About one-third of women with epilepsy experience an increase in a seizure. The relationship between seizure frequency before pregnancy and increased seizures during parturition were studied by many clinical studies, as well as epilepsy and pregnancy registries, and it shows that the effect of pregnancy may vary from one patient to another and in different pregnancies of the same patient. It was also found that the seizures were more frequent in pregnancies with a male (64%) as opposed to a female (30%) neonate (Knight and Rhind, 1975). Some women might not experience any seizures during pregnancy, others might have a fluctuation of seizures while others experience unchanged seizures during this period.
The management of epilepsy during pregnancy is difficult because both the maternal and the fetus are at risk (Viinikainen et al., 2006). The seizures control treatment needs to be improved by introducing new and safer AEDs. There is no evidence regarding the non-teratogenic AEDs or that may lack developmental toxicity. Although, independent studies have reported a substantial risk for malformations associated with the valproic acid drug as compared with other AEDs. Women with epilepsy who are planning pregnancy should avoid the use of the valproic acid drug. Although, there are some women with juvenile myoclonic epilepsy, where seizure control is only maintained by the valproic acid drug. In this case, it should be noted that a low dose of this drug may not be harmful compared to other drugs (Battino and Tomson, 2007).