Should you take anticonvulsants while pregnant? What does the latest research say about anticonvulsants and pregnancy? Sadly there isn't much research on anticonvulsants and being pregnant. Researchers on pregancy and anticonvulsants have repeatedly taken note of the need for good research on this topic. One has to use caution. The following are the lastest research abstracts I have found on anticonvulsants and pregnancy
Am J Obstet Gynecol. 2004 Feb;190(2):371-9. :
Epilepsy and pregnancy: an obstetric perspective.
Richmond JR, Krishnamoorthy P, Andermann E, Benjamin A.
Department of Obstetrics and Gynecology, Women's Pavilion, Royal Victoria Hospital, McGill University, Montreal, Quebec, CanadaOBJECTIVE: The purpose of this study was to determine the obstetric and neonatal outcomes of women with prepregnancy diagnoses of epilepsy. STUDY DESIGN: This was a cohort study of women with epilepsy (n=414 women) who were delivered in a tertiary referral center (1978-2000). Outcomes were compared with women who did not have epilepsy (n=81,759 women) who were delivered during the same period, with the use of t tests or contingency table analyses. RESULTS: Comparison showed increased rates of nonproteinuric hypertension (P<.05), induction of labor (P<.001), and fetal cardiovascular malformations (P<.001) among women with epilepsy. Rates of other antenatal, intrapartum, and neonatal complications and congenital malformations were similar to those of control subjects. There were fewer instrumental vaginal deliveries. There were no live births with neural tube defects. The occurrence of major antepartum seizures did not increase the rate of adverse outcomes significantly. Major congenital malformations increased in proportion to the number of anticonvulsants that were prescribed. CONCLUSION: Women with epilepsy are not at increased risk for obstetric complications, provided that appropriate care is available during preconception, pregnancy, labor, delivery, and after delivery
Bipolar Disord. 2003 Jun;5(3):189-202. Related Articles, Links
Valproate.
Bowden CL.
Department of Psychiatry, The University of Texas Health Science Center at San Antonio, 78229, USA. bowdenc@uthscsa.edu
OBJECTIVES: This article summarizes the role of valproate as a treatment for bipolar disorder and related conditions. METHODS: Published studies and reviews were systematically reviewed. Results from randomized, parallel group, double-blind, placebo-controlled studies that included an active comparator are emphasized. RESULTS: Valproate is an effective treatment for manic patients. Valproate was superior to placebo in one 1-year randomized, parallel group study in rate of recurrence requiring discontinuation, rate of depression requiring discontinuation, total early termination and time to 25% of patients relapsing with mania, and in controlling mild depressive symptoms. On some measures, including time to development of a manic episode, valproate did not differ from placebo. Assessments of maintenance efficacy of valproate and other putative prophylactic treatments for bipolar disorder are problematic, because of the need to analyze multiple indices of efficacy, and practical and ethical issues that limit generalizability of results of placebo-controlled studies. Valproate has some advantages over lithium in treatment of mania for persons with more severe illnesses. Valproate benefits a broader spectrum of bipolar conditions than lithium. Valproate appears at best modestly effective for bipolar depression. Used in combination with several other treatments, additive benefits result, that are greater than with any of the treatments as monotherapy. Side effects are generally mild and manageable, particularly with divalproex. Weight gain and pharmacokinetic interaction with lamotrigine are perhaps the most consistent problems in use. Valproate contributes to neural tube defects if taken during the first trimester of pregnancy, and this risk must be conveyed to women. CONCLUSIONS: Valproate is an effective and useful treatment for bipolar disorder. Studies clarifying its spectrum of efficacy, its safety and efficacy in combination regimens, and its mechanisms of action are warranted.
Acta Neurol Scand. 2004 Jan;109(1):9-13.
Epilepsy and pregnancy: lamotrigine as main drug used.
Sabers A, Dam M, A-Rogvi-Hansen B, Boas J, Sidenius P, Laue Friis M, Alving J, Dahl M, Ankerhus J, Mouritzen Dam A.
Danish Epilepsy Hospital, Dianalund, Denmark.
anns@glostruphosp.kbhamt.dk
OBJECTIVES: To study the risk of teratogenicity in infants of women with epilepsy. MATERIAL AND METHODS: Prospective data from 1996 to 2000 comprised 147 pregnancies. The most frequent antiepileptic drugs (AEDs) used were lamotrigine (LTG) 35% (n = 51), oxcarbazepine (OXC) 25% (n = 37) and valproate (VPA) 20% (n = 30). Seventy-four per cent (n = 109) received monotherapy. Folic acid supplementation was taken during first trimester by 118 patients (80%). RESULTS: The overall risk of malformations among newborns in the AED-exposed group was 3.1% (n = 4). Two children were born with multiple malformations (VPA monotherapy), two children had ventricular septal defects (one OXC monotherapy, and one OXC and LTG). The risk of malformations was 2.0% in women treated with LTG and 6.7% in women treated with VPA (NS). CONCLUSION: Despite the small number of cases in the study these data indicate that treatment with LTG during pregnancy might be relatively safe. Larger prospective studies are needed to obtain adequate power for statistical analysis.
Mutat Res. 2003 Jan 10;534(1-2):197-9.
Valproic acid and lamotrigine treatment during pregnancy. The risk of chromosomal abnormality.
Ozkinay F, Cogulu O, Gunduz C, Yilmaz D, Kultursay N.
Department of Paediatrics, Faculty of Medicine, Ege University, Izmir, Turkey.
egetam@med.ege.edu.tr
A baby born to an epileptic mother had dysmorphological features associated with 47,XXX karyotype. The mother had been treated with valproic acid (1800mg per day) and lamotrigine (100mg per day) throughout pregnancy. Dysmorphological features detected in baby were intrauterine growth retardation, hypertelorism, flattened nasal bridge, low set malformed auriculas, micrognathia, very small an bow-shaped mouth with thin upper lip, cleft palate, arachnodactyly, camptodactyly, secundum atrial septal defect, bilateral hammer toes and decreased creases on the soles. At 6 months old she showed motor retardation. The molecular analysis of parents revealed that extra X chromosome was inherited from the mother. In this case whether the dysmorphological features and 47,XXX karyotype were caused by lamotrigine and valproic acid treatment during pregnancy or coincidence is in question.
Epilepsia. 2002 Oct;43(10):1161-7. :
Preliminary results on pregnancy outcomes in women using lamotrigine.
Tennis P, Eldridge RR; International Lamotrigine Pregnancy Registry Scientific Advisory Committee.
Worldwide Epidemiology Department, GlaxoSmithKline, Research Triangle Park, North Carolina 27709, USA.
PST49347@gsk.com
PURPOSE: In 1992, the International Lamotrigine Pregnancy Registry was initiated to enroll prospectively and to monitor pregnancies exposed to lamotrigine (LTG) for the occurrence of major birth defects. This study presents results as of September 2001 on 168 outcomes exposed to LTG monotherapy and 166 outcomes after pregnancies exposed to LTG polytherapy during the first trimester. METHODS: LTG pregnancy exposures are voluntarily reported to the registry by health care providers before they are aware of each pregnancy outcome. Pregnancy-outcome ascertainment is obtained through subsequent follow-up with the reporting health care provider, and each reported birth defect is reviewed by an expert pediatrician. The percentage with major birth defects in pregnancies with known birth defect status was calculated for LTG monotherapy and for polytherapy stratified by trimester of exposure. RESULTS: The registry identified 334 first-trimester LTG pregnancy outcomes exposed to LTG monotherapy or polytherapy during the first trimester and involving either a live birth with or without a major birth defect or an abortion with a major birth defect. After exposure to LTG monotherapy, the percentage with major birth defects exposed to LTG monotherapy was three (1.8%) of 168 [95% confidence interval (CI), 0.5-5.5%]. There were five (10%) major birth defects observed in 50 outcomes after LTG polytherapy involving valproic acid (VPA; 95% CI, 3.7-22.6%) during the first trimester. The observed proportion of major defects after LTG polytherapy without VPA during the first trimester was five (4.3%) of 116 (95% CI, 1.6-10.3%). No specific patterns of major birth defects in any subgroup or within the registry as a whole were observed. CONCLUSIONS: The sample sizes for individual regimens are too small to rule out small increases in frequency of all major birth defects or even large increases in frequency of rare major birth defects. However, the percentage of outcomes with major birth defects after LTG monotherapy in this study and in another similar pregnancy registry in the United Kingdom did not differ from that reported in the recent literature for women with epilepsy receiving antiepileptic drug monotherapy (4%). The frequency of major malformations after exposures of LTG-VPA is higher than that after the LTG monotherapy or LTG polytherapy regimens without VPA. Although there are published data on frequency of major malformations after VPA exposures in pregnancy, between-study differences in methods and source populations and the wide confidence intervals around the estimate for LTG and VPA limit the utility of comparison with such data, and no conclusions are made at this time about this combination. The continued registration of exposed pregnancies to an exposure registry as early as possible in the pregnancy before any knowledge of the outcome, and before any prenatal testing, will enhance the power of such data.
Eur J Clin Pharmacol. 2003 Feb;58(10):677-82. Epub 2003 Jan 30.
Transplacental passage of lamotrigine in a human placental perfusion system in vitro and in maternal and cord blood in vivo.
Myllynen PK, Pienimaki PK, Vahakangas KH.
Department of Pharmacology and Toxicology, University of Oulu, PO Box 5000, FIN-90014, Oulu, Finland.
paivi.k.myllynen@oulu.fi
OBJECTIVE: We studied transplacental passage of lamotrigine (3,5-diamino-6-[2,3-dichlorophenyl]-1,2,4-triazine; LTG) using an ex vivo human placental perfusion method and in in vivo samples. METHODS: Term placentas from healthy mothers without medications were perfused in a recirculating dual perfusion system. LTG (2.5 microg/ml, n=4; 10 microg/ml, n=4) and reference compound antipyrine (100 microg/ml) were added into the maternal circulation. The disappearance of drugs from the maternal circulation and appearance into the foetal circulation was followed every 15 min up to 2 h. Drug concentrations were analysed using high-performance liquid chromatography. In addition to human placental perfusions, we analysed LTG concentrations in maternal vein and cord blood samples after delivery from two epileptic mothers receiving LTG therapy during pregnancy. RESULTS: LTG was detectable in the foetal circulation at 15 min in all of the perfusions, indicating rapid transfer. Maternal and foetal concentrations reached equilibrium at 60 min with both concentrations used. The feto-maternal ratio was 1.26+/-0.20 with 10 microg/ml LTG and 0.83+/-0.41 with 2.5 microg/ml LTG at the end of the perfusion. The transfer of LTG from the maternal to the foetal compartment at 120 min was 28.9+/-10.7% with 2.5 microg/ml LTG and 37.8+/-3.2% with 10 microg/ml LTG (p>0.05). In the serum samples from epileptic mothers, the cord blood maternal concentration ratio was 1.02 in one pair and 1.55 in the other. CONCLUSIONS: LTG crossed the placenta easily and rapidly, indicating that the maternal treatment leads to a considerable foetal exposure.
Neurology. 2004 Jan 13;62(1):28-32. :
Comment in:
Neurology. 2004 Jan 13;62(1):8-9.
Normal intelligence in children with prenatal exposure to carbamazepine.
Gaily E, Kantola-Sorsa E, Hiilesmaa V, Isoaho M, Matila R, Kotila M, Nylund T, Bardy A, Kaaja E, Granstrom ML.
Hospital for Children and Adolescents, 00029 HUS, Finland.
eija.gaily@hus.fi
OBJECTIVE: To investigate the effect of antiepileptic drugs, especially carbamazepine and valproate, on intelligence in prenatally exposed children of mothers with epilepsy. METHODS: Intelligence of 182 children of mothers with epilepsy (study group) and 141 control children was tested in a blinded setting at preschool or school age using Wechsler Preschool and Primary Scale of Intelligence-Revised or Wechsler Intelligence Scale for Children-Revised. Data on maternal antiepileptic treatment and seizures during pregnancy were gathered prospectively. The study group represented approximately 50% of the children born to mothers with epilepsy in Uusimaa province during 1989 through 1994. One hundred seven children were exposed to antiepileptic monotherapy: 86 to carbamazepine and 13 to valproate. Thirty children were exposed to polytherapy: 23 combinations included carbamazepine, and 17 included valproate. The median maternal doses and blood levels during the second half of pregnancy were 600 mg and 26 micro mol/L for carbamazepine and 950 mg and 300 micro mol/L for valproate. RESULTS: The mean verbal and nonverbal IQ scores in the children exposed in utero to carbamazepine monotherapy were 96 (95% CI, 93-100) and 103 (95% CI, 100-106). They did not differ from control subjects, whose mean verbal and nonverbal IQ scores were 95 (95% CI, 92-97) and 102 (95% CI, CI, 100-105). Significantly reduced verbal IQ scores were found in children exposed to valproate (mean, 82; 95% CI, 78-87) and to polytherapy (mean, 85; 95% CI, 80-90) compared with the other study group children and control subjects. CONCLUSIONS: Carbamazepine monotherapy with maternal serum levels within the reference range does not impair intelligence in prenatally exposed offspring. Exposures to polytherapy and to valproate during pregnancy were associated with significantly reduced verbal intelligence. The independent effects of valproate remain unconfirmed because the results were confounded by low maternal education and polytherapy.
1: Rev Neurol. 2003 Dec 1-15;37(11):1022-8. Related Articles, Links
[Use of anticonvulsive drugs during pregnancy and the risk of malformations in the newborn: a meta-analysis]
[Article in Spanish]
Gutierrez-Alvarez AM.
Oficina de Investigaciones, Facultad de Medicina, Universidad Colegio Mayor de Nuestra Senora del Rosario, Bogota, Colombia. amgutier@claustro.urosario.edu.co
OBJECTIVE: To determine the risk, if any, of anticonvulsants use on the foetus with respect to major malformations. MATERIALS AND METHODS: MEDLINE, EMBASE, SCISEARCH and programs as ProQuest, HINARI and Ovid were searched for human studies. Studies that examined the effects of systematic exposure to any anticonvulsant during pregnancy (any dose, any duration, indicated for any type of epilepsy) were eligible. Studies that assessed major malformations in the infants were eligible. Major malformations were defined using the criteria described by Holmes. The number of neonates exposed to anticonvulsants who did and did not exhibit major malformations, and the number of neonates not exposed to anticonvulsants who did and did not exhibit major malformations, were extracted in the form of 2 x 2 tables. The odds ratio (OR), relative risk and 95% confidence interval (CI) was calculated for each of the studies. RESULTS: Ten cohort studies and four case control studies were included. A total of 2,509 cases and 433,890 controls were included. Major malformations were found in 9.8% among the exposed children and 7.4% among the non exposed. (OR: 2.7; CI 95%: 2.062-3.641; p<0.000). There was no evidence of an association between any anticonvulsant and a specific major malformation. CONCLUSIONS: The available epidemiological data support the hypothesis that anticonvulsants increase the risk of major malformations by an order of 2- to 3-fold.
Obstet Gynecol. 2003 Nov;102(5 Pt 2):1215-7. :
Anticonvulsant hypersensitivity reaction in pregnancy.
Deering SH, Thompson K, Taylor J, Hueppchen N.
Department of Obstetrics and Gynecology, National Naval Medical Center, Bethesda, Maryland, USA.
deering95@hotmail.com
BACKGROUND: Anticonvulsant hypersensitivity reaction is a multisystem disorder that occurs after exposure to aromatic anticonvulsants. It is potentially fatal, with a mortality rate up to 50%. We report a case of an anticonvulsant hypersensitivity reaction that occurred during pregnancy at 10 weeks' gestation. CASE: A grand multipara was being treated with carbamazapine for a seizure disorder. She developed a maculopapular rash, elevated liver enzymes, and pancytopenia. Withdrawal of aromatic anticonvulsants and supportive therapy resulted in resolution of her illness. The remainder of her pregnancy was uneventful, and she delivered a healthy infant at term. CONCLUSION: All pregnant women treated with aromatic anticonvulsants are at risk for anticonvulsant hypersensitivity reaction, and a high degree of clinical suspicion is essential for diagnosis.
Neurology. 2003 Jun 10;60(11 Suppl 4):S31-8. :
The importance of monotherapy in pregnancy.
Pennell PB.
Epilepsy Monitoring Unit, Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA.
The great majority of women with epilepsy who become pregnant have normal pregnancies and healthy infants. However, in utero exposure to antiepileptic drugs (AEDs) can put infants of women with epilepsy at increased risk for a variety of abnormalities, including intrauterine growth retardation, minor anomalies, major congenital malformations, microcephaly, and cognitive dysfunction. Various combinations of these findings can occur in an individual infant and are referred to as the fetal anticonvulsant syndrome (FAS). The most common major malformations are cleft lip/palate, heart defects, neural tube defects, and urogenital defects. Although AEDs have teratogenic risks, withdrawal of all AEDs before pregnancy is not a realistic option for many women with epilepsy. The results of several studies indicate that AED monotherapy reduces the risk for development of FAS compared with polytherapy exposure in utero. Current treatment guidelines advise use of AED monotherapy when possible and folate supplementation beginning before and continuing throughout pregnancy. Prenatal screening for major malformations should be offered. Careful planning and management of any pregnancy in women with epilepsy is essential to increase the likelihood of a healthy outcome for mother and infant.
Ann N Y Acad Sci. 2003 May;993:103-14; discussion 123-4. :
Antiepileptic drugs and apoptosis in the developing brain.
Bittigau P, Sifringer M, Ikonomidou C.
Department of Pediatric Neurology, Children's Hospital, Charite-Virchow Clinics, Humboldt University, Berlin, Germany.
petra.bittigau@charite.de
Epilepsy is the most common neurologic disorder in young humans. Antiepileptic drugs (AEDs), used to treat seizures in children, infants, and pregnant women, cause cognitive impairment, microcephaly, and birth defects by unknown mechanisms. We tested whether common AEDs cause neurodegeneration in the developing rat brain. Rats aged 3-30 days received phenytoin, phenobarbital, diazepam, clonazepam, vigabatrin, or valproic acid. Histologic examination of the brains revealed that these drugs cause widespread and dose-dependent apoptotic neurodegeneration in the developing rat brain during the brain growth spurt period. Apoptotic neurodegeneration was triggered at plasma drug levels relevant for seizure control in humans. Antiepileptic drugs lead to reduced expression of neurotrophins and decreased concentrations of the active forms of ERK1/2, RAF, and AKT. beta-Estradiol, which stimulates pathways that are activated by neurotrophins, ameliorated AEDs-induced apoptotic neurodegeneration. Our findings present one possible mechanism to explain cognitive impairment and reduced brain mass associated with pre- or postnatal exposure of humans to antiepileptic therapy.
Eur J Epidemiol. 2003;18(8):769-71. :
Comment in:
Eur J Epidemiol. 2003;18(8):743-4.
Psychomotor development in children exposed in utero to benzodiazepines, antidepressants, neuroleptics, and anti-epileptics.
Mortensen JT, Olsen J, Larsen H, Bendsen J, Obel C, Sorensen HT.
Department of Clinical Epidemiology, Aarhus University and Aalborg Hospitals, Stengade 10, Box 561, Aalborg, Denmark.
jenstm@dadlnet.dk
We did a follow-up study based upon a regional prescription register in Denmark. We identified all 435 women who in the period 1991-1996 had redeemed a prescription for CNS drugs during pregnancy. Among the rest of the pregnant women we randomly selected 1304 women who also had given birth to a child in the same region and period. We looked up the local health nurses Boel test results which were available for about 80%. Any abnormal test result was seen much more frequently among exposed (16%) than for not exposed (4%). The study has several limitations but raises concern that should be addressed in other and better designed studies.
Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):15089-94. Epub 2002 Nov 04.:
Antiepileptic drugs and apoptotic neurodegeneration in the developing brain.
Bittigau P, Sifringer M, Genz K, Reith E, Pospischil D, Govindarajalu S, Dzietko M, Pesditschek S, Mai I, Dikranian K, Olney JW, Ikonomidou C.
Department of Pediatric Neurology, Children's Hospital, Charite-Virchow Clinics, Humboldt University, Augustenburger Platz 1, 13353 Berlin, Germany.
Epilepsy is the most common neurological disorder of young humans. Each year 150,000 children in the United States experience their first seizure. Antiepileptic drugs (AEDs), used to treat seizures in children, infants, and pregnant women, cause cognitive impairment, microcephaly, and birth defects. The cause of unwanted effects of therapy with AEDs is unknown. Here we reveal that phenytoin, phenobarbital, diazepam, clonazepam, vigabatrin, and valproate cause apoptotic neurodegeneration in the developing rat brain at plasma concentrations relevant for seizure control in humans. Neuronal death is associated with reduced expression of neurotrophins and decreased concentrations of survival-promoting proteins in the brain. beta-Estradiol, which stimulates pathways that are activated by neurotrophins, ameliorates AED-induced apoptotic neurodegeneration. Our findings present one possible mechanism to explain cognitive impairment and reduced brain mass associated with prenatal or postnatal exposure of humans to antiepileptic therapy.
Rev Neurol. 2002 Sep;35 Suppl 1:S135-43. :
[Teratogenic effects of epilepsy and anti epileptic drugs]
[Article in Spanish]
Campistol J.
Servicio de Neurologia, Unitat Integrada de Pediatria Hospital Sant Joan de Deu-Cliinic. Universitat de Barcelona, Barcelona, Espana.
campistol@hsjdbcn.og
OBJECTIVE: In this paper we review the main studies on teratogenicity related to epilepsy and especially use of anti epileptic drugs (AED), with special emphasis on recently acquired knowledge regarding the new AED. DEVELOPMENT: When considering the teratogenic effects of epilepsy and the anti epileptic drugs it should be remembered that there are a series of premises and considerations which undoubtedly play an important part in causing possible damage to the foetus. These factors include changes caused during pregnancy, the passage of drugs across the placenta barrier , malformations occurring in the children and relations of women with epilepsy and finally the effect of seizures on the foetus. We then review the mechanisms of the teratogenicity of the classical AED and the new AED. Little is known about the adverse effects of the new AED, and many are used together as polytherapy. Multicenter studies involving large numbers of participants are therefore necessary to obtain results which can be extrapolated to the whole population. Unfortunately, at present, this is not yet so and there are no clear recommendations for their use during pregnancy. The EURAP was designed for this reason. It is one of the multicenter studies being carried out in Europe at present with many Spanish specialists participating. CONCLUSIONS: Multicenter studies with many participants are necessary to obtain reliable data on the teratogenicity of the various AED, used as monotherapy and bitherapy, particularly regarding the new AED. We conclude by considering measures to try to reduce, as far as possible, the teratogenic effects in pregnant women.
Del Med J. 2002 Mar;74(3):127-35. :
Diazepam use during pregnancy: a review of the literature.
Iqbal MM, Sobhan T, Aftab SR, Mahmud SZ.
Department of Psychiatry & Behavioral Neurobiology, School of Medicine, University of Alabama at Birmingham, USA.
Antianxiety medications such as benzodiazepines (BZDs) are frequently and appropriately used to ameliorate the anxiety symptoms of depression, dysthymic disorder, panic disorder, agoraphobia, obsessive-compulsive disorder, generalized anxiety disorder, eating disorder, and many personality disorders. Pregnancy may be accompanied by anxiety necessitating therapeutic intervention by anxiolytic drugs like BZD. Keeping in view the potential risks of teratogenicity and direct neonatal toxicity, BZDs with established safety records should be used, while avoiding exposure in the first trimester, especially with multidrug regimens, and prescribing the lowest dose for the shortest duration. This literature review highlights information from various sources regarding safety data of exposure of pregnant and lactating mothers to long-acting BZDs, especially diazepam.
Neurol Neurochir Pol. 2002 Mar-Apr;36(2):259-66. :
[Analysis of epileptic pregnant women delivering between 1992-1998 in obstetric departments of the University Medical School in Lublin]
[Article in Polish]
Stelmasiak Z, Semczuk W, Nowicka-Tarach B, Halczuk I, Semczuk-Sikora A, Laskowska M.
Katedry i Kliniki Neurologii Akademii Medycznej w Lublinie.
Pregnancy in woman with epilepsy arouses several serious medical problems and always belongs to the group of high obstetric risks. The aim of the present clinical study was the evaluation of the antiepileptic treatment efficiency during pregnancy, including risk factor, effects on pregnancy and delivery in epileptic patients. The study group consisted of 84 epileptic pregnant women which delivered between 1992-1998 in Obstetric Departments of University Medical School of Lublin. A randomised group 80 healthy pregnant women constituted the control group. The mean age of the analysed patients was 25 years. 51 epileptic patients were pregnant for the first time, 23 patients for the second time and 10 patients for the third time or more. The mean duration time of the disease was 8.6 years. In our study group: 45 (53.8%) patients experienced primary generalized tonic-clonic seizures and 39 (46.6%) patients experienced partial seizures. 26 patients were treated with monotherapy and the rest with polytherapy methods. The estimation of the seizure frequency during pregnancy in 52 (61.9%) patients did not change, in 13 (15.4%) patients increased. Among obstetric complications: urinary tract infections, hypertonia (EPH-gestosis) were observed. In 4 newborn congenital defects have been noted. Mothers of three of them were treated with Phenydantin (heart lesion, developmental anomaly of fingers). The fourth mother used Convulex (meningoarachnided hernia, hydrocephalus).
Rev Neurol. 2002 Mar 1-15;34(5):476-80.
[Malformations in the offspring of pregnant women with epilepsy. Presentation of an international registry of antiepileptic drugs and pregnancy (EURAP)]
[Article in Spanish]
Battino D, Mamoli D, Messina S, Perucca E, Tomson T.
Istituto Neurologico Carlo Besta, Milan, Italia.
dbattino@istituto-besta.it
The interaction between epilepsy and pregnancy has been studied for many years; nonetheless the risk associated with individual antiepileptic drug has not been adequately characterized up to date. Moreover, virtually nothing is known about the possible human teratogenicity of the newer antiepileptic drugs. Because of the complexity of the mechanisms involved, the crucial evidence needed can only come from very large population based studies, and a collaborative European multicentre investigation has been set up to this purpose. Specific objectives include the evaluation of the risk of major foetal malformations and of delay in prenatal growth following exposure to antiepileptic drugs, assessment of the pattern of congenital abnormalities associated with older and newer antiepileptic drugs and their combinations, and identification of possible relationships with dosage and with a variety of other risk factors. All women exposed to antiepileptic drugs at the time of conception are eligible for entry. The protocol is purely observational and does not entail any change in prescribing pattern or management policies, which are left to the discretion of the treating physician. Data obtained during prospective monitoring for up to 1 year after birth are regularly collected in especially designed forms and entered into Regional Registries prior to transfer to a Central European Registry of Antiepileptic Drugs and Pregnancy (EURAP). Evaluations of incidence and prevalence of teratogenic endpoints will be based exclusively on cases enrolled before foetal outcome is known and in any case not after the 16th week of pregnancy. Cases enrolled after birth, after the 16th week of pregnancy or after prenatal diagnosis will only be reported descriptively. The study is being implemented gradually in 19 countries in Western and Eastern Europe. Wide participation from interested physicians is essential for the achievement of the study objectives, which are expected to lead to important advances in pre pregnancy counselling and overall clinical management of women with epilepsy.
CNS Drugs. 2002;16(11):755-64. ;
Teratogenic potential of the newer antiepileptic drugs: what is known and how should this influence prescribing?
Palmieri C, Canger R.
Regional Epilepsy Center, University of Milan Medical School, San Paolo Hospital, Milan, Italy.
The treatment of women of childbearing age who have epilepsy raises many questions because of the interactions between epilepsy, antiepileptic therapy and different aspects of reproductive life. Menstrual cycle disorders and reduced fertility have been partially ascribed to antiepileptic drugs (AEDs). Furthermore, most AEDs induce the cytochrome P450 (CYP) enzymatic system, altering the metabolism of sex hormones and contributing to the failure of oral contraceptives. Pregnancy represents, in this context, the most critical period because of the well known teratogenic potential of all established AEDs. For most of these drugs no specific patterns of malformations have been identified, although during the past few decades basic knowledge has been acquired, particularly concerning the mechanisms of AED-induced teratogenesis and related risk factors. These issues form the basis of the current guidelines for the management of epilepsy in pregnant women. In the past decade, several new AEDs have been introduced into clinical practice. For a number of reasons, these drugs appear to be more favourable than the older ones as treatments for epilepsy in women of childbearing age. They possess a good pharmacokinetic profile that makes them more stable during pregnancy, and they have a low potential for interaction with other drugs. They are also less likely than the older AEDs to be metabolised to compounds that are teratogenic. Furthermore, most of them do not possess antifolate properties. With the exception of topiramate and vigabatrin, the newer AEDs do not appear to be teratogenic in animals when administered in subtoxic doses. However, animal teratology may not be a reliable predictor of human teratogenicity, and there is a significant lack of information regarding the teratogenic profile of these newer agents in humans. Because clinical experience with these agents is limited, it is advisable to avoid exposure of the embryo to these drugs when pregnancy is planned. The establishment of pregnancy registries could allow for the rapid collection of data related to the administration of new AEDs in pregnancy and the outcomes of such exposure.
