Outcomes of pregnancy associated with antiepileptic drugs. Maternal and obstetric outcome of women with epilepsy Pregnancy outcome in women exposed to antiepileptic drugs: teratogenic role of maternal epilepsy and its pharmacologic treatment. Population based, prospective study of the care of women with epilepsy in pregnancy Community-based, prospective, controlled study of obstetric and neonatal outcome of 179 pregnancies in women with epilepsy. In utero antiepileptic drug exposure Factors influencing the risk of abnormal pregnancy outcome in epileptic women: A multi-centre prospective study [Evaluation of antiepileptic therapy during pregnancy]. Epilepsy, pregnancy, and major birth anomalies: an Italian prospective, controlled study.
OBJECTIVE To determine whether exposure to antiepileptic drugs during pregnancy is associated with poor fetal outcomes ( anomalies and death ) and to assess the relative risks with phenobarbital , phenytoin sodium , and carbamazepine . DESIGN The design was a prospect i ve case-control cohort study of pregnant women with epilepsy and their offspring . Outcomes were compared with those of a control group of 355 healthy women and their offspring . SETTING The obstetrics service at Los Angeles County/University of Southern California Medical Center , Los Angeles , a large , inner-city , teaching hospital . PATIENTS Two hundred eleven subjects who were pregnant during the years 1987 through 1990 , 174 of whom were delivered of infants , were available for analysis . A control group of 355 healthy women and their offspring from the same hospital were r and omly selected from a computerized data base . INTERVENTION None . MAIN OUTCOME MEASURE Anomalies and fetal death were the primary outcome measures . RESULTS Offspring of women with epilepsy who were exposed to antiepileptic drugs had a higher rate of fetal death and anomalies than did the control population ( P = .001 ) . Abnormal outcomes were associated with the three major antiepileptic drugs ( carbamazepine , phenytoin , and phenobarbital ) . In terms of abnormal outcome ( death and anomalies ) , phenobarbital was associated with the highest relative risk , phenytoin with intermediate relative risk , and carbamazepine with the lowest relative risk ( P = .019 ) . Numbers were insufficient for assessment of risk associated with valproic acid . CONCLUSION All three major antiepileptic drugs ( phenobarbital , phenytoin , and carbamazepine ) are associated with an increased risk of fetal death and anomalies . We found phenobarbital to be most associated with poor pregnancy outcome UNLABELLED Medical professionals and public are concerned about the complications of pregnancy and delivery in women with epilepsy ( WWE ) . PURPOSE Our aim was to prospect ively ascertain occurrence of these complications in a cohort of WWE enrolled in a pregnancy registry . METHODS All complications during pregnancy , delivery and first 48 h of postpartum period were recorded according to the registry protocol . This data were compared with similar statistics ( for women without epilepsy ) from a large teaching hospital . RESULTS Between April 1998 and March 2005 , there were 643 completed pregnancies in this registry . ( Mean age 25.7+/-4.43 years ; generalized epilepsy 46 % ; localization related epilepsy 54 % ; primigravida 53 % . ) Their complications are compared with those of 18,272 pregnancies managed in the teaching hospital ( in parentheses ) . Spontaneous abortions 4.2 % ( 2.38 % ) ; medical termination of pregnancies 2.64 % ( 7.71 % ) ; anemia 0.62 % ( 0.22 % ) ; gestational diabetes 1.56 % ( 3.09 % ) ; pregnancy induced hypertension 3.89 % ( 6.45 % ) ; antepartum hemorrhage 0.93 % ( 1.64 % ) ; preterm labor 1.87 % ( 6.12 % ) ; obstructed labor 0.62 % ( 3 % ) ; cesarean section 33.4 % ( 29.5 % ) ; assisted delivery 2.8 % ( 2.68 % ) ; postpartum hemorrhage 0.31 % ( 0.64 % ) ; peripartum seizures 1.4 % ( 0.04 % ) ; intrauterine death 1.56 % ( 2.2 % ) ; fibroid uterus or ovarian cyst 2.33 % ( 0.53 % ) ; other medical illness 2.5 % ( 2.15 % ) ; TORCH infection 0.31 % ( 0.01 % ) ; birth weight < 2.0 kg 4.19 % ( 7.66 % ) . CONCLUSIONS There was no significant increase in the risk of complications of pregnancy or delivery except for spontaneous abortions , anemia , ovarian cyst , fibroid uterus , and seizures in the peripartum period which were more frequent in WWE . Frequency of cesarean section is not increased in WWE . There is no undue risk to pregnancy and childbirth in most WWE Infants born to epileptic women treated with antiepileptic drugs ( AEDs )  have an increased risk of major congenital malformations ( MCMs ) . In order to determine the role of maternal epilepsy we conducted a prospect i ve cohort study on three cohorts of pregnant women : ( i ) 385 epileptic women treated with AEDs , ( ii ) 310 non-epileptic women treated with AEDs , ( iii ) 867 healthy women not exposed to AEDs ( control group ) . The rate of MCMs in the epileptic group ( 7.7 % ) was not statistically higher than in the non-epileptic one ( 3.9 % ) ( p=0.068 ) . The rate in the first group was higher compared to the control group ( p=0.001 ) , while the rate in the second one was not ( p=0.534 ) . Our data confirm that AEDs therapy is the main cause of the increased risk of malformations in the offspring of epileptic women ; however a teratogenic role of the maternal epilepsy itself can not be excluded This prospect i ve , population based study in the former Northern health region was design ed to establish the proportion of pregnant women with a history of epilepsy ; doctors supervising their care ; effectiveness of preconceptional counselling and control of epilepsy ; and use of medication and pregnancy outcomes . The project had approval from regional ethics committees . Pregnant women with epilepsy were recruited to the study , predominantly by community midwives . Women who consented were interviewed by using a st and ard question naire . Hospital notes were review ed after the women had given birth . General practice and hospital notes were checked in one area to confirm the women 's response regarding preconceptional advice . Between 1 January 1997 and 31 December 1998 , 400 notifications of pregnancies to women with epilepsy were received ( the total number of livebirths , stillbirths , and medical terminations for this period was 65 478 , giving a proportion of all pregnancies to women with epilepsy of 6.1/1000 ) . View this table : Malformations seen in relation to use of drugs Three hundred women were interviewed , 60 did not consent PURPOSE This study evaluated obstetric and neonatal outcome in a community-based cohort of women with active epilepsy ( WWAE ) compared with the general pregnant population receiving modern obstetric care . METHODS We review ed the total population who gave birth between January 1989 and October 2000 at Kuopio University Hospital . Obstetric , demographic , and epilepsy data were collected prospect ively from 179 singleton pregnancies of women with epilepsy and from 24,778 singleton pregnancies of unaffected controls . The obstetric data from the pregnancy register was supplemented with detailed neurologic data retrieved from the medical records . The data retrieved were comprehensive because of a follow-up strategy according to a predecided protocol . RESULTS During pregnancy , the seizure frequency was unchanged , or the change was for the better in the majority ( 83 % ) of the patients . We found no significant differences between WWAE and controls in the incidence of preeclampsia , preterm labor , or in the rates of caesarean sections , perinatal mortality , or low birth weight . However , the rate of small-for-gestational-age infants was significantly higher , and the head circumference was significantly smaller in WWAE . Apgar score at 1 min was lower in children of WWAE , and the need for care in the neonatal ward and neonatal intensive care were increased as compared with controls . The frequency of major malformations was 4.8 % ( -0.6 - 10.2 % ; 95 % confidence interval ) in the 127 children of WWAE . CONCLUSIONS Pregnancy course is uncomplicated and neonatal outcome is good in the majority of cases when a predecided protocol is used for the follow-up of WWAE in antenatal and neurologic care . Long-term follow-up of the neurologic and cognitive development of the children of WWAE is still needed Background : Pregnancy outcomes following in utero exposure to antiepileptic drugs ( AEDs ) are uncertain , limiting an evidence d-based approach . Objective : To determine if fetal outcomes vary as a function of different in utero AED exposures . Methods : This ongoing prospect i ve observational study across 25 epilepsy centers in the USA and UK enrolled pregnant women with epilepsy from October 1999 to February 2004 to determine if differential long-term cognitive and behavioral neurodevelopmental effects exist across the four most commonly used AEDs . This initial report focuses on the incidence of serious adverse outcomes including major congenital malformations ( which could be attributable to AEDs ) or fetal death .  A total of 333 mother/child pairs were analyzed for monotherapy exposures : carbamazepine ( n = 110 ) , lamotrigine ( n = 98 ) , phenytoin ( n = 56 ) , and valproate ( n = 69 ) . Results : Response frequencies of pregnancies result ing in serious adverse outcomes for each AED were as follows : carbamazepine 8.2 % , lamotrigine 1.0 % , phenytoin 10.7 % , and valproate 20.3 % . Distribution of serious adverse outcomes differed significantly across AEDs and was not explained by factors other than in utero AED exposure . Valproate exhibited a dose-dependent effect . Conclusions : More adverse outcomes were observed in pregnancies with in utero valproate exposure vs the other antiepileptic drugs ( AEDs ) . These results combined with several recent studies provide strong evidence that valproate poses the highest risk to the fetus . For women who fail other AEDs and require valproate , the dose should be limited if possible We studied pregnancy outcome in preconceptionally recruited epileptic and control women in a multi-centre prospect i ve non-intervention study at two university hospitals and three general hospitals . We evaluated 225 singleton pregnancies : 119 pregnancies of epileptic women who received either antiepileptic drugs ( AEDs ) ( n = 99 ) or not ( n = 20 ) , and 106 pregnancies of controls . The main outcome measures were abnormal pregnancy outcome : major and minor congenital malformations , ectopic pregnancies , abortions ; neonatal headcircumference ; birth weight and birth length .  Epileptic women had a two-fold risk of having an abnormal pregnancy outcome or an infant with minor malformations compared to healthy controls ( odds ratio , with 95 % confidence interval , respectively 2.1 ( 1.1 , 4.0 ) and 2.0 ( 1.0 , 4.0 ) ) . A significant correlation between the prevalence of abnormal pregnancy outcome and duration of epilepsy and AED treatment was found ( risk increased by 9 % ( 6 % , 16 % ) per annum ) . No significant effect in terms of the type , the number or the serum level of the AEDs could be established . The head circumference of infants of epileptic mothers was significantly smaller ( 0.7 ( 1.2 , 0.28 cm ) compared to controls . An effect on the outcome of pregnancy of maternal folate supplementation or of folate blood concentrations during the periconceptional period and first trimester of pregnancy could not be determined . The severity of maternal epilepsy and /or AED treatment influences pregnancy outcome OBJECTIVE The aim of the study was to analyse the course of pregnancy and labour in women with epilepsy . MATERIAL AND METHODS The study was carried out on 53 pregnant women with epilepsy who delivered in the Department of Obstetrics and Perinatology of the University School of Medicine in Lublin ( group E ) . RESULTS In the group of women with epilepsy there were observed more pregnancy complications . The mean birth weight of infants and the condition of the infant after birth evaluated were lower in the study group E according to Apgar score . The increased risk of congenital malformations and intrauterine foetal growth retardation were observed in children exposed to valproate or carbamazepine in monotherapy or combination of phenobarbital and phenytoin and the combination of phenobarbital , phenytoin and primidone in polytherapy . CONCLUSION Women with epilepsy require appropriate pregnancy planning and appropriate neurologic and obstetric care preconceptionally and during pregnancy We followed prospect ively 97 women with epilepsy during 138 pregnancies and 88 women without epilepsy , matched for age , during 140 pregnancies . We evaluated seizure frequency , pregnancy outcome , and presence of major congenital malformations , and correlated them with the type of epilepsy , antiepileptic drugs ( AEDs ) implicated , plasma AED levels during pregnancy , and maternal age . We compared the two groups regarding type and number of pregnancies ; complications during gestation , labor , and delivery ; prevalence of abortions ( spontaneous or induced ) ; perinatal deaths ; and type and prevalence of major malformations . No change in seizure frequency during pregnancy was seen in 79.7 % of cases . Pregnancy complications and incidence of major congenital malformations were only slightly higher in women with epilepsy than in women without epilepsy . No single AED used as monotherapy correlated with increased risk of malformations , but polypharmacy with phenobarbital and phenytoin seemed to represent a risk factor . Low socioeconomic status , older age at delivery , and family history of malformations were other risk factors for neonatal malformations
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