The use of anticonvulsants during pregnancy.

Antiepilepsy (AED) medications have revolutionized the treatment of epilepsy, transforming it from a chronic progressive disease with inevitable cognitive and motor decline to a disorder in which most effected persons operate largely in a normal fashion. As with all medications adverse experiences can occur. However, it has been clear that the alternative of uncontrolled seizures are more hazardous than pharmacological therapies. However, physicians are faced with a dilemma when treating fertile or pregnant women with epilepsy. Many AED impair the effectiveness of oral contraceptives. There is evidence that some AED may effect fertility. AED metabolism changes in pregnancy, making management of women with epilepsy more difficult. AED exposure in early pregnancy increases the risk of congenital malformations, and exposure during other phases may increase the risk of developmental delay and neonatal hemorrhage. AED can be secreted in breast milk, thus extending the exposure into infancy. The exclusion of women of childbearing age from clinical trials limits our ability to collect information on the pharmacokinetics and potential adverse experiences of AED in pregnancy. Thus, when new medications are marketed, clinicians and their patients have no information on how to best manage conception, pregnancy, and lactation. This article discusses these issues in detail and describes our current understanding of the use of AED in women of childbearing age.     

Complications during pregnancy in women with epilepsy: population-based cohort study

Objective  To investigate whether women with epilepsy have an increased risk of complications during pregnancy and to explore the impact of antiepileptic drug (AED) use.
Design  Population-based cohort study.
Setting  Data from Medical Birth Registry of Norway based on all births in Norway 1999–2005.
Population  All births ( n  = 372 128) delivered in Norway, ensured through linkage with the National Population Registry run by Statistics Norway. All singleton births and the first child in multiple pregnancies were included, leaving 365 107 pregnancies for analyses.
Main outcome measures  Pre-eclampsia (mild and severe), gestational hypertension, eclampsia, vaginal bleeding (early and late) and preterm birth.
Results  We compared 2805 pregnancies in women with a current or past history of epilepsy (0.8%) and 362 302 pregnancies in women without a history of epilepsy. Women with epilepsy had an increased risk of mild pre-eclampsia, [odds ratio 1.3: 95% confidence interval (1.1–1.5)] and delivery before week 34 [1.2: (1.0–1.5)].
Antiepileptic drugs were used in 33.6% ( n  = 942) of the pregnant women with epilepsy. Compared to women without epilepsy, women with epilepsy and AED use had an increased risk of mild pre-eclampsia [1.8: (1.3–2.4)], gestational hypertension [1.5: (1.0–2.2)], vaginal bleeding late in pregnancy [1.9: (1.1–3.2)], and delivery before 34 weeks of gestation [1.5: (1.1–2.0)]. No significant increase in the risk of these complications was observed in women with epilepsy not using AED. These results remained unchanged after exclusion of multiple pregnancies.
Conclusion  Women with epilepsy have a low complication rate, but special attention should be paid to those using AED during pregnancy.     

The Australian Register of Antiepileptic Drugs in Pregnancy: the first 1002 pregnancies

BACKGROUND: Prospective studies are needed to assess the maternal and fetal hazards of antiepileptic drug (AED) therapy in pregnancy. AIMS: To make the Australian Register of AEDs in Pregnancy better known to the Australian obstetric community by presenting results derived from it. METHODS: Analysis of data collected by the Register between 1999 and December 2006. RESULTS: The Register contained data on 1002 epileptic or AED-treated pregnancies, 992 with known outcomes, 83 not exposed to AEDs in at least their first trimester, and 30 prescribed AEDs for indications other than epilepsy. Statistically significant findings included more frequent folate supplementation and decreased alcohol intake during pregnancy in women with epilepsy; a dose-related increased risk of fetal malformation associated with valproate therapy; a tendency towards lower birthweights in live-born malformed offspring; and a substantially reduced decreased risk of seizures in pregnancy with one year seizure freedom before pregnancy. The small numbers of patients may have prevented other differences from reaching a P<0.05 value. CONCLUSIONS: The Register has already produced important information for the management of pregnant women with epilepsy in Australia, but greater rates of recruitment into the Register are desirable to allow it to achieve its full potential.     

Women with epilepsy planning pregnancy

There are many important health issues for women with epilepsy, in particular for women of childbearing age. Recent surveys have shown that only a minority of such patients received information on important issues concerning pregnancy. Pre-pregnancy counselling should include information on interactions of antiepileptic drugs (AEDs) and oral contraceptives, risk of teratogenicity, use of folic acid, the importance of monotherapy with the lowest effective dosage of an AED, and the safety of breast feeding as well as other special aspects of epilepsy and pregnancy. Planned pregnancy and counselling before conception is crucial. With a multidisciplinary approach the majority of pregnancies will have a favourable outcome. The article addresses these issues and describes practical considerations for the counselling of women with epilepsy who are planning pregnancy.     

EURAP-Register ? Antiepileptika in der Schwangerschaft

In Europe, approximately 0.5% of women suffer from epilepsy. Many of those women are unsure about the risks with antiepileptic treatment during pregnancy. The European Registry of Antiepileptic drugs in Pregnancy (EURAP) is an international project which collects prospective information about pregnancies with exposure to antiepileptic drugs. The aim is to gain more information about the safety and risks of different antiepileptic drugs and to compare them in terms of the frequency of major malformations or prenatal growth retardation. At present there are 7,555 pregnancies registered (May, 2011).The rate of major malformations is about 6% after exposure to antiepileptic drug (AED) monotherapy. Lamotrigine seems to have a relatively lower teratogenic risk and is therefore preferred as an antiepileptic medication during pregnancy. Levetiracetam showed a low malformation rate of 2.5% but the numbers are too low to give a final statement about the safety in pregnancy. Unfortunately, less than 20% of suitable women have been registered in EURAP. As EURAP is a global network, collaboration of the responsible physicians is essential for the growing success of the EURAP registry.     

Current management in pregnancy and epilepsy

Modern treatments make possible uneventful pregnancy and successful delivery for most of the epileptic women. Major risks however remain the teratogenic effects of some antiepileptic drugs and the obstetric complications they may cause. This implies careful planning of pregnancy for women with epilepsy and alertness for possible unwanted or undiagnosed (in the early stages) pregnancy in epileptic women during their reproductive years. The authors summarize current opinions in drug selections, specific treatment regimens and the obstetrics problems during pregnancy and delivery in epileptic women.     

妊娠合并癫痫

癫痫严重影响母胎结局,增加围产期发病率及母胎死亡率,而抗癫痫药物的使用增加胎儿先天畸形发生率。为此,合理使用抗癫痫药物是妊娠合并癫痫管理的关键。应注意尽可能单一用药,避免使用丙戊酸钠及苯妥英钠,以最低有效剂量控制癫痫发作,规律检测血药浓度,适时调整剂量。     

Using ultrogestan for the treatment of spontaneous abortions and complications of climax in women with epilepsy

Epilepsy is a disease, closely connected with sex-hormones and can lead to adverse repercussion on the reproductive health. The ovarial hormones influence excitation of neurocells membranes and have a lot of effects on brain, leading to provoking epileptic activity. The progesteron decrease and the estrogens increase the brain excitation, that's why estrogens (act like a proconvulsant) are proconvulsant and progesteron is anticonvulsant. The aim of this study is to evaluate therapeutic abilities of Utrogestan (micronising progesteron) for treatment of abortions and climacteric amplifications in women with epilepsy. The study is prospectiv and includes 21 women with epilepsy, treated with Utrogestan. The women are divided into two groups: 1-st group --12 pregnant women with symptoms of aborts and 2-nd group--9: 6 with climacteric blooding and 3 with hormone replacement therapy on the occasion of postcastration syndrome. In 13 patients drug is applied through mouth and in 8--through vagina. The vaginal way is used in patients, that accept enzyminductiv antiepilepsy drugs (AED). Utrogestan was applied preventive in 10 pregnant women with symptoms of danger of abortion and in two women with a medicinal aim. In 10 patient pregnancy finished successful with delivery of a healthy child on term, in one--pregnancy is in progress, in one was made interruption. There weren't epilepsy attacks in no one pregnant women, that may be connected with both adequate treatment of epilepsy and with influence of micronising progesteron as anticonvulsant. In the 2-nd group in 4 women with climacteric blooding Utrogestan is applied vaginal from 15-24 day of menstruation to retrieve regularity of cycles. In 3 women with postcastration syndrome Utrogestan is used as a part of hormone substitute treatment (Oestrogel and Utrogestan once a day continuously. The treatment was with very good effect, without changes in the frequency and weight of the epileptic attacks. Results of our study show, that Utrogestan has very good effect in treatment of women with epilepsy. With his natural, herbal origin and micronisation form, as well as possibilities for oral and vaginal application of the same form, Utrogestan tends to take the place of synthetic progesteron analogs, when epilepsy have had a bad influence over reproductive health.     

Use of phenytoin in pregnancy for epileptic seizure prevention: a case report

Epilepsy is the most common neurological disorder in women of reproductive age. Phenytoin is one of the most frequently prescribed antiepileptic drugs. Although the vast majority of women with epilepsy have normal pregnancy outcomes, certain fetal anomalies and pregnancy complications are associated with epilepsy and phenytoin use. Appropriate midwifery care of women with epilepsy includes consultation and co-management with an obstetrician and a neurologist. The clinical course of a woman with epilepsy taking phenytoin is presented.     

Prescribing in pregnancy. Epilepsy in pregnancy

In women with epilepsy, seizure control during pregnancy can be improved by maintaining the serum anticonvulsant drug concentration within the therapeutic range. Treatment with one anticonvulsant drug plus folic acid supplementation 5 mg per day seems appropriate in most cases. This should be achieved before conception whenever possible. No anticonvulsant drug seems free of teratogenic risk. With the commonly used anticonvulsant drugs-phenytoin, phenobarbitone, carbamazepine and sodium valproate-the risk is relatively low and represents less potential harm to the fetus than might occur with uncontrolled seizures.     

A fit in a woman who is 32 weeks pregnant

A fit in pregnancy may be the result of epilepsy, eclampsia or acute systemic illness. In most cases seizures stop rapidly but may be life threatening, particularly if not self-limiting. Obstetricians should be familiar with the causes of fits in pregnancy and have clear guidelines for diagnosis and treatment. In this article the differential diagnosis and management of a fit in pregnancy are discussed. Specific guidelines are proposed for epilepsy, eclampsia and status epilepticus.     

The treatment of neonatal seizures: focus on Levetiracetam

Neonatal crises are a common problem in the first month, where phenobarbital and phenytoin are still the most frequently used medication in treatment. Whereas, Levetiracetam (LEV) is an antiepileptic drug (AED) with an innovative action. Our present review is updated on the current literature regarding the use of LEV in neonatal seizures treatment. The available data is analyzed to assess LEV pharmacokinetics, efficacy and tolerability in neonatal crises treatment. Several clinical trials, prospective and retrospective, comparative and pharmacokinetic studies were evaluated in LEV pharmacokinetics, efficacy, dosage, route of administration and side effects. Many cases were reported on neonatal seizures control in using LEV in certain clinical conditions. In spite of the limitations in current studies available, which have evaluated LEV efficacy and safety in neonatal crises treatment, the authors still believe that LEV seems to be a promising and useful AED in the treatment for neonatal seizures, but likewise further studies are required to better define LEV efficacy and tolerability in term and preterm neonates.     

Anticonvulsants and drugs for neurological disease

The use of anticonvulsant drugs in pregnancy presents unique challenges to clinicians and their patients. The need for control of maternal epilepsy must be balanced with the fetal and neonatal risks associated with anticonvulsant drugs. Anticonvulsant drugs may have potential effects on embryogenesis, neurological development, growth and subsequent paediatric progress. Drug selection and dose adjustment must be appropriate and based on a combination of known maternal and fetal risks as well as the clinical status of the patient. Overall, no one drug can be specifically recommended but monotherapy with most of the recognized first-line drugs will result in a satisfactory outcome. Polytherapy is associated with an increase in congenital malformations and should be avoided if possible. It is possible that newer second-line agents, for example, gabapentin, may be safer as add-on therapy.Neurological disorders such as migraine, and the less common conditions of myasthenia gravis and multiple sclerosis, may require the use of drugs which have not been well studied in pregnancy. Information is provided about the use of drugs to control symptoms and prevent disease progression in these disorders during pregnancy.     

Prenatal vitamin K1 administration in epileptic women to prevent neonatal hemorrhage: is it effective?

OBJECTIVE: To summarize current knowledge on whether prenatal prophylactic vitamin K1 administration to epileptic women receiving enzyme-inducing antiepileptic drugs (AEDs) to prevent neonatal hemorrhage is effective. STUDY DESIGN: A computerized MEDLINE search was conducted using the terms antiepileptic drug, hemorrhagic disease of the newborn, pregnancy and vitamin K since 1966 to July 2004, limited only to human studies. English-language publications were selected based on their relevance to the clinical effectiveness of administration of oral vitamin K to epileptic women exposed to enzyme-inducing AEDs for prevention of hemorrhagic disease of the newborn (HDN). RESULTS: No randomized, controlled trial testing prenatal vitamin K1 administration for reducing the incidence or severity of neonatal hemorrhage was identified. This review summarizes the data from published observational studies. CONCLUSION: There is inadequate evidence to recommend the routine administration of prenatal vitamin K to epileptic women exposed to enzyme-inducing AED therapy in order to prevent HDN.     

Neonatal outcome in infants of epileptic mothers

The effect of epilepsy and anti-epileptic treatment on neonatal outcome was investigated in 86 pregnancies terminating in delivery. Various maternal and neonatal parameters were considered. Each infant born to an epileptic mother was double-matched with two infants born to healthy mothers and the results were sumbitted for statistical analysis. Infants of epileptic mothers had smaller head circumference. Primidone was the only anti-epileptic drug, taken during pregnancy, to have a significant effect on infant head circumference. The results suggest that a drug effect, rather than an association with maternal epilepsy, is responsible for this difference. Hypertelorism is the only congenital anomaly to be significantly more frequent in newborns of epileptics. All drugs, except for primidone, were associated significantly with this anomaly. Further similar studies and prolonged follow-up of the infants of epileptic mothers are necessary before drawing any final conclusions regarding the outcome of these infants.     

Drugs in pregnancy. Anticonvulsants and drugs for neurological disease.

The use of anticonvulsant drugs in pregnancy presents unique challenges to clinicians and their patients. The need for control of maternal epilepsy must be balanced with the fetal and neonatal risks associated with anticonvulsant drugs. Anticonvulsant drugs may have potential effects on embryogenesis, neurological development, growth and subsequent paediatric progress. Drug selection and dose adjustment must be appropriate and based on a combination of known maternal and fetal risks as well as the clinical status of the patient. Overall, no one drug can be specifically recommended but monotherapy with most of the recognized first-line drugs will result in a satisfactory outcome. Polytherapy is associated with an increase in congenital malformations and should be avoided if possible. It is possible that newer second-line agents, for example, gabapentin, may be safer as add-on therapy. Neurological disorders such as migraine, and the less common conditions of myasthenia gravis and multiple sclerosis, may require the use of drugs which have not been well studied in pregnancy. Information is provided about the use of drugs to control symptoms and prevent disease progression in these disorders during pregnancy.     

Do Women with Epilepsy Have More Fear of Childbirth During Pregnancy Compared with Women without Epilepsy? A Case‐Control Study

ABSTRACT: Background: Although anxiety and depression in populations with epilepsy have been studied, no research on fear of childbirth in women with epilepsy have been conducted. The purposes of this study were to examine whether a significant difference occurred in fear of childbirth between pregnant women with epilepsy and pregnant healthy controls and to evaluate the most common fears. Methods: Fifty pregnant women with epilepsy and 50 pregnant women without epilepsy were assessed at a gestational age between 32 and 36 weeks of pregnancy, using two questionnaires for the measurement of fear of childbirth, an open question, and a clinical interview. Results: We found that during pregnancy, women with epilepsy experienced a significantly higher rate of fear of childbirth when compared with healthy controls, whereas after delivery, the experiences and feelings about childbirth are almost the same as those of women without epilepsy. Conclusions: Our findings signify the importance of the assessment of the fear of childbirth, especially in women with epilepsy, and the need to offer professional and ad hoc support to those who suffer from it. (BIRTH 35:2 June 2008)     

Neurological disease in pregnancy

Neurological disease encompasses a broad spectrum of conditions which may be affected by pregnancy, present de novo in pregnancy, or are caused by the pregnancy itself. Neurological diseases remain the second most common cause of indirect maternal deaths in the UK. It is imperative that a thorough history and examination are performed when assessing pregnant women presenting with neurological conditions, and that early specialist advice is sought. Multidisciplinary team working is also integral when caring for these women. These points are highlighted with the aid of case studies, with a particular focus on epilepsy, headaches, stroke, multiple sclerosis and myasthenia gravis in pregnancy.     

Psychiatric and nervous disorders

There has recently been increased occasions to treat patients complicated with psychiatric and nervous disorders, in accordance with the rise of interest in human right and the improved social acceptance of these diseases. In the past, most cases were reluctantly terminated because of the prejudice against diseases and anxiety about the teratogenicity of the drugs. In this paper, the management of pregnancy and delivery including neonatal period are discussed. 1) Epilepsy Epilepsy is one of the most common medical complications of pregnancy with about 0.5%. Pregnancy has no obvious effect on epilepsy. Although the teratogenicity of the antiepileptic drugs has been repeatedly reported, anticonvulsant therapy should be continued during pregnancy. Because the risk of the fetal brain damage from hypoxia under the epileptic convulsion of the untreated patients is higher than that of the teratogenicity of drugs. Phenobarbital or phenytoin are commonly used. Trimethadione which has been used for the petit mal epilepsy should not be used because of the high potent of teratogenicity. The serum concentrations of these drugs tend to decrease in the third trimester. Therefore the frequent monitoring of the serum drug concentration is very important. The monitoring of the blood clotting factors after delivery is also very important to avoid the neonatal vitamin K deficiency bleeding. Vitamin K is administered if required. Breast feeding is not contraindicated. Withdrawal syndrome in the neonatal state should not be overlooked. 2) Schizophrenia Pregnancy has no effect on schizophrenia. The teratogenicity of chlorpromazine or haloperidol in human pregnancy is thought to be negative. The function of the fetal central nervous system is suppressed with antipsychotic drugs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Contraception for Women with Epilepsy

Purpose of Review

The purpose of this review is to summarize the current available literature on contraception for women with epilepsy, and to provide recommendations for women with epilepsy on enzyme-inducing anti-seizure drugs and on non-enzyme-inducing anti-seizure drugs.

Recent Findings

A recent study has confirmed the safety of the levonorgestrel-containing intrauterine device for women with epilepsy, with no effect on seizure control or anti-seizure drug levels. Other recent studies have found low serum etonogestrel or levonorgestrel levels in women on enzyme-inducing anti-seizure drugs and the etonogestrel or levonorgestrel implant, making this an unsuitable method for women on such drugs.

Summary

Women with epilepsy have an especially compelling need to avoid unplanned pregnancy, as some common anti-seizure medications have teratogenic or detrimental neurocognitive effects on exposed children. Women on enzyme-inducing anti-seizure drugs and their physicians must be particularly aware of drug interactions with hormonal contraceptive methods.