Management of Epilepsy during Pregnancy

Fondazione I R C C S Istituto Neurologico Carlo Besta, Milan, Italy.
Drugs (Impact Factor: 4.34). 01/2007; 67(18):2727-46. DOI: 10.2165/00003495-200767180-00007
Source: PubMed


Managing epilepsy during pregnancy is to balance the maternal and fetal risks associated with uncontrolled seizures against the potential teratogenic effects of antiepileptic drugs (AEDs). A rational approach requires knowledge of such risks as well as an understanding of the effects of pregnancy on seizure control and of gestational effects on AED disposition. Uncontrolled tonic-clonic seizures are potentially hazardous to the mother and, although strict evidence is lacking, are generally also assumed to be more harmful to the fetus than are AEDs. However, infants who have been exposed to AEDs in utero run an increased risk of congenital malformations: approximately twice the rate reported in the general population. Earlier literature has largely failed to demonstrate differences in birth defect rates with different treatment regimens, which can be ascribed mainly to insufficient sample sizes. More recent data have indicated higher malformation rates with exposure to valproic acid compared with some other major AEDs. The teratogenic effects of valproic acid appear to be dose dependent, with higher risks at dosage levels >1000 mg/day. Polytherapy involving treatment with more than one AED also seems to be associated with an increased risk of birth defects compared with monotherapy. Recently, a few small-scale studies have investigated the possibility that exposure to AEDs in utero may adversely affect the postnatal cognitive development of the offspring. Some of these studies have suggested that valproic acid poses a higher risk compared with other AEDs in this respect. These signals are important, but must be interpreted with caution because of the methodological shortcomings of the studies and because adequately powered prospective studies are necessary to draw firm conclusions. More reassuring findings have emerged regarding the obstetric outcome of pregnancy and the risk of worsening of epilepsy during pregnancy. In particular, it seems that the risk of obstetric complications is not significantly increased. Furthermore, most of the women with epilepsy have no change in their seizure frequency during pregnancy. The disposition of many AEDs may change during pregnancy, reflected in declining plasma drug concentrations. This seems to be most pronounced for lamotrigine and possibly also for oxcarbazepine, and can result in break-through seizures. The common treatment strategy has been to use the appropriate AED for the woman's seizure disorder as monotherapy in the lowest effective dosage throughout pregnancy, the objective being to use AEDs in such a way that generalised tonic-clonic seizures are avoided but with minimised risks to the fetus, the newborn and the breast-fed infant. Valproic acid should be avoided if possible. Any major change in the treatment of a woman with epilepsy should ideally be completed before conception. Regular monitoring of drug concentrations is recommended during pregnancy, in particular for lamotrigine and oxcarbazepine.

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    • "Epilepsy is the most common neurologic condition that requires continuous management during pregnancy and AEDs are associated with increased risk of teratogenicity in this population [6]. The management of epilepsy during pregnancy requires a balance between minimizing fetal exposure to AEDs and maintaining seizure control [7]. Although it has been reported that ZNM is teratogenic in animals, very limited data are available on the extent of teratogenicity in humans and further clinical investigations are warranted to confirm the preliminary findings [8, 9]. "
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    ABSTRACT: Pregnancy is associated with various physiological changes which may lead to significant alterations in the pharmacokinetics of many drugs. The present study was aimed to investigate the potential effects of pregnancy on the pharmacokinetic profile of zonisamide (ZNM) in the rabbit. Seven female rabbits were used in this study. The pregnant and nonpregnant rabbits received ZNM orally at a dose of 10 mg/kg and blood samples were collected from the animals just before receiving the drug and then serially for up to 24 h. The plasma samples were analyzed using tandem mass spectrometric method. Following a single oral dose of ZNM to the rabbits, the mean values of ZNM plasma concentrations at different times were consistently low in pregnant compared to nonpregnant rabbits. The mean values of ZNM's C max and AUC0-∞ were significantly (P < 0.05) decreased, whereas the CL/F exhibited substantial increase (P < 0.05) in pregnant compared to nonpregnant rabbits. T max, t 1/2abs, t 1/2el, MRT, and Vd/F showed no significant differences between the two groups. The present study demonstrates that pregnancy decreased ZNM plasma concentrations in rabbits and that the decrease could be due to decreased extent of gastrointestinal absorption, induced hepatic metabolism, or enhanced renal elimination of the drug.
    12/2013; 2013:140327. DOI:10.1155/2013/140327
    • "There is a higher risk in children of mothers with polytherapy compared to monotherapy and occasionally a clear relationship between daily dose and risk of malformations has been documented.[7] Selected drugs are thought to be associated with specific malformations.[8] "
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    ABSTRACT: Approximately 1% of all pregnancies are in woman with epilepsy. Although, the majority of children born to women with epilepsy are normal, they are at increased risk for malformations. Notably, the teratogenicity of antiepileptic drugs is a well-defined subject. The incidence of major malformations in offspring of mothers with epilepsy who were treated with AEDs is higher than women with untreated epilepsy and in the general population. These malformations include spina bifida, cleft palate, limb reduction defects, cardiac abnormalities, hypospadias, and gastrointestinal atresia. The exact mechanism by which the AEDs mediate abnormalities in the fetus is uncertain. However, there are several hypotheses to explain them. Some of the most important include folate-related actions, ischemia, reactive intermediates (e.g., free radicals), and genetic susceptibility. Thus, understanding the mechanisms of AED-related abnormalities is of vital importance for the care of epileptic women and their offspring.
    Journal of research in medical sciences 09/2012; 17(9):876-81. · 0.65 Impact Factor
    • "Although both of the seizures and AEDs seem to be risk factors for complications during pregnancy, but there are some controversies about their importance. Some studies shown a little role for epileptic attacks,[3–6] while the others reported that uncontrolled tonic--clonic seizures could be harmful for the mother and the fetus than are AEDs.[16] "
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    ABSTRACT: Epilepsy is a rare neurologic disorder during pregnancy. Despite its rarity, it could cause different clinical problems in this natural phenomenon of a woman's life. The aim of this study was to evaluate and compare the course of pregnancy and labor and their outcome in epileptic and healthy women. This study was performed during years 2009--2011 in Alzahra and Beheshti hospitals affiliated to Isfahan University of Medical Sciences. A total of 51 pregnant women, who were known cases of epilepsy and were on antiepileptic drugs treatment for at least 3 months, were compared with 47 matched healthy pregnant women without epilepsy. They were followed before and during their pregnancy in several visits and all of their neurologic and obstetric information were collected. For statistical analysis of continuous variables, the t-test was used. The chi-square test was used for dichotomous variables. The rate of monotherapy was more than polytheraphy especially during the pregnancy. The epileptic attacks stopped in majority of patients during the pregnancy. Vaginal bleeding (P=0.020) and abortion (P=0.015) were significantly more frequent among epileptic mothers. The gestational age was lower meaningfully (P= 0.010) in epileptic patients' neonates and the first minute Apgar score was lower in these babies too (P=0.028). Antiepileptic drugs could have some unsuitable effects on pregnancy course especially by increasing the rate of abortion, preterm labor, and vaginal bleeding. Their adverse effects on neonates' health could not be neglected.
    03/2012; 1(1):4. DOI:10.4103/2277-9175.94426
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