Antiepileptic Drugs In Pregnancy Research Articles

MANAGING ANTI-EPILEPTIC DRUGS DURING PREGNANCY ; EVOLVING CONCEPT

Epilepsy is one of the few neurological disorders that require a constant treatment during pregnancy.Besides epilepsy Anti-epileptic drugs (AEDs) are also commonly used for psychiatric disorders,pain disorders,and migraines. No Anti-epileptic drugs is safe during pregnancy . Anti-epiletic drugs exposure during pregnancy causing intra- uterine growth retardation,cognitive dysfunction,low IQ,microcephaly,major conjenital anomalies and infant mortality. Use of anti-epileptic drugs (AEDs) in pregnant women with epilepsy requires monitorning and maintaining a balance between limiting seizures and decreasing fetal exposure to the potential teratogenic effects. In this review we analysed the data on the pharmacokinetics of various AEDs in pregnancy, neurological teratogenic effects and providing a basis for management of safety of AEDs during pregnancy

Fetal malformations in successive pregnancies in Australian women with epilepsy

ObjectivesTo utilize data from the Australian Register of Antiepileptic Drugs in Pregnancy (APR) to determine the hazard of fetal malformation in the subsequent pregnancy or pregnancies in women with epilepsy following a pregnancy associated with a fetal malformation, and to identify factors relevant to the hazard. ResultsThere was a 7.4% initial pregnancy fetal malformation rate. The subsequent pregnancy malformation rate was 4.2% if there was no initial pregnancy malformation, but 21.2% if there was an initial pregnancy malformation (O.R. = 6.1448, 95% C.I. 2.3396, 16.1386). For pregnancies where antiseizure medication (ASM) therapy was unchanged between pregnancies (N = 196), the initial pregnancy malformation rate was 10.2%, but 30.0% in the subsequent pregnancy if there was a malformation in the initial pregnancy, and 2.35% if there was none (O.R. = 17.7857, 95% C.I. 4.4847, 70.5361). A cohort comprising 24% of the women with fetal malformations in their initial pregnancies seemed to be intrinsically vulnerable to fetal malformation during successive pregnancies: when their seizure disorder type had been recorded all had genetic generalized epilepsies, compared with a 45.8% generalized epilepsy rate in women with initial but not subsequent pregnancy malformations (P = 0.0121). ConclusionsIf fetal malformation had occurred in an initial ASM-treated pregnancy there was a significantly increased hazard of fetal malformation in the subsequent pregnancy, particularly if the woman involved had a genetic generalized epilepsy.

Association of Prenatal Exposure to Antiseizure Medication With Risk of Autism and Intellectual Disability

Women with epilepsy frequently need antiseizure medication (ASM) to prevent seizures in pregnancy. Risk of neurodevelopmental disorders after prenatal exposure to AMSs is uncertain. To determine whether children exposed prenatally to ASMs in monotherapy and duotherapy have increased risk of neurodevelopmental disorders. The Nordic register-based study of antiepileptic drugs in pregnancy (SCAN-AED) is a population-based cohort study using health register and social register data from Denmark, Finland, Iceland, Norway, and Sweden (1996-2017; analysis performed February 2022). From 4 702 774 alive-born children with available mother-child identities and maternal prescription data, this study included 4 494 926 participants. Children from a multiple pregnancy or with chromosomal disorders or uncertain pregnancy length were excluded (n = 207 848). Prenatal exposure to ASM determined from maternal prescription fills between last menstrual period and birth. We estimated cumulative incidence at age 8 years in exposed and unexposed children. Cox regression adjusted for potential confounders yielded adjusted hazard ratios (aHRs) with 95% CIs for autism spectrum disorder (ASD), intellectual disability (ID), or any neurodevelopmental disorder (ASD and/or ID). A total of 4 494 926 children were included; 2 306 993 (51.3%) were male, and the median (IQR) age at end of follow-up was 8 (4.0-12.1) years. Among 21 634 unexposed children of mothers with epilepsy, 1.5% had a diagnosis of ASD and 0.8% (numerators were not available because of personal data regulations in Denmark) of ID by age 8 years. In same-aged children of mothers with epilepsy exposed to topiramate and valproate monotherapy, 4.3% and 2.7%, respectively, had ASD, and 3.1% and 2.4% had ID. The aHRs for ASD and ID after topiramate exposure were 2.8 (95% CI, 1.4-5.7) and 3.5 (95% CI, 1.4-8.6), respectively, and after valproate exposure were 2.4 (95% CI, 1.7-3.3) and 2.5 (95% CI, 1.7-3.7). The aHRs were elevated with higher ASM doses compared with children from the general population. The duotherapies levetiracetam with carbamazepine and lamotrigine with topiramate were associated with increased risks of neurodevelopmental disorders in children of women with epilepsy: levetiracetam with carbamazepine: 8-year cumulative incidence, 5.7%; aHR, 3.5; 95% CI, 1.5-8.2; lamotrigine with topiramate: 8-year cumulative incidence, 7.5%; aHR, 2.4; 95% CI, 1.1-4.9. No increased risk was associated with levetiracetam with lamotrigine (8-year cumulative incidence, 1.6%; aHR, 0.9; 95% CI, 0.3-2.5). No consistently increased risks were observed for neurodevelopmental disorders after prenatal exposure to monotherapy with lamotrigine, levetiracetam, carbamazepin, oxcarbazepine, gapapentin, pregabalin, clonazepam, or phenobarbital. In this cohort study, prenatal exposure to topiramate, valproate, and several duotherapies were associated with increased risks of neurodevelopmental disorders.

Achieving neurologically desirable outcomes to pregnancy in women with epilepsy

ObjectivesTo investigate possible factors that influenced whether pregnancy in women with epilepsy resulted in the desirable outcome of a live-born non-malformed infant and a mother whose pregnancy had been seizure free. ResultsThe desirable outcome, as defined, occurred in 46.3% of unselected pregnancies in the database of the Australian Register of Antiepileptic Drugs in Pregnancy (APR). The only factor investigated that had a statistically significant (P < 0.05) effect, increasing the chance of such a desirable outcome, was freedom from seizures in the pre-pregnancy year. However, anti-seizure medication (ASM) doses, particularly valproate doses, had been reduced prior to 15.6% of the pregnancies, and this may have concealed factors that otherwise may have adversely affected the desirable outcome rate. Analysis of data for monotherapy with the more commonly used ASMs appears to suggest that employing levetiracetam at the outset of antiseizure therapy may offer a better chance of a desirable outcome to future pregnancies than monotherapy with other ASMs, but this finding is not confirmed statistically. ConclusionsIn pregnancies where valproate use has already been minimized, seizure control throughout the pre-pregnancy year was associated with the best chance of a desirable outcome, as defined above. In most Australian women starting therapy for epilepsy initiating treatment with levetiracetam monotherapy may offer the best chance of such a desirable outcome to a future pregnancy, yet to be confirmed.

Everything you need to know about sodium valproate and other antiepileptic drugs in pregnancy

Sodium valproate is a broad-spectrum anticonvulsant drug that has been on the UK market since 1973​[1]​. In the UK, it is licensed for the treatment of epilepsy and bipolar disorder and can also be considered in patients with episodic or chronic migraine​[2]​. Commonly used brands in the UK include Dyzantil (Aspire Pharma), Epilim (Sanofi), Episenta […]

Pregnancy outcomes in women with surgically treated epilepsy

To ascertain whether epileptic seizure control during pregnancy differed between Australian women with previously surgically treated epilepsy, and those with only medically treated epilepsy. Analysis of data for 74 pregnancies of women with surgically treated focal epilepsy, compared with that from 1013 pregnancies in women with medically treated focal epilepsy, both groups drawn from the Australian Register of Antiepileptic Drugs in Pregnancy between 1999 and 2020. Seizures of all types, and also convulsive seizures, were less well controlled during pregnancy in the previously surgically treated cases, the difference for seizures of all types (68.9% versus 50.1%) being statistically significant (p<.05). This result was contrary to the outcome of a previously published study of the same question carried out in India. At present, it may be premature to conclude that previous epilepsy surgery will be associated with a better chance of seizure-free, or seizure-controlled, pregnancy.

Some antiepileptic drugs are safer than others for use during pregnancy, MHRA review concludes

Lamotrigine and levetiracetam are safer than other antiepileptic drugs in pregnancy because they are not linked with an increased risk of birth abnormalities compared with the general population, according to a safety review by the Medicines and Healthcare products Regulatory Agency (MHRA). Carbamazepine, phenobarbital, phenytoin and topiramate were all found to be associated with an increased […]

Folic acid dose, valproate, and fetal malformations

ObjectiveTo determine whether there is a relationship between folic acid dose and the degree of protection against valproate-associated and other antiepileptic drug (AED)-associated fetal structural malformations in women with AED-treated epilepsy. MethodsStatistical analysis of data from the Raoul Wallenberg Australian Register of Antiepileptic Drugs in Pregnancy involving 2104 folic acid-treated pregnancies in women with epilepsy. ResultsMultiple variable logistic regression failed to demonstrate any statistically significant effect of folic acid dosage in reducing overall fetal malformation rates in women taking folic acid either before and during pregnancy (P = 0.640) or during early pregnancy only (P = 0.801), and in reducing spina bifida occurrence rates (P = 0.409). ConclusionsIn the present state of knowledge, it would seem misguided to hope that a folic acid dose of 5 mg/day taken before and during pregnancy would protect against the occurrence of valproate-associated and other AED-associated fetal structural malformations. Future studies are required to determine whether high-dose periconceptional folate use may decrease the risk of other valproate-associated adverse fetal outcomes, including impaired post-natal neurobehavioral development.

Twin pregnancy in women with epilepsy.

We report data from the Raoul Wallenberg Australian Register of Antiepileptic Drugs in Pregnancy (APR) to see if there are significant differences in relation to the courses and outcomes of the twin pregnancies contained in the register, as compared with the singleton ones. The APR has been under the oversight of Melbourne institutional Human Ethics Research Committees; all women enrolled in the APR have provided written informed consent. Data from the APR were transferred to a spreadsheet and then analyzed using simple statistical techniques including logistic regression. The population studied comprised 44 twin and 2261 singleton pregnancies; thus, twin pregnancies accounted for 1.91% of all pregnancies studied. The women carrying twins tended to be older than the women with singleton pregnancies to a statistically significant extent, their pregnancies more often originated from assisted fertilization techniques, and their babies were more often delivered by cesarean section. There were no statistically significant differences in relation to antiepileptic drug (AED) therapy. Individual twins had statistically significantly lower mean birthweights than singleton babies and they were statistically significantly more often involved structurally malformed foetuses. In the first year of life, the twin pregnancies statistically significantly more often produced offspring that were affected by seizures in infancy. The data suggest that there may be an increased hazard of fetal malformation in the offspring of twin pregnancy in women with epilepsy, but that with contemporary standards of management of epilepsy and pregnancy, there is unlikely to be an increased hazard of seizure-affected pregnancy.

Antiepileptic drugs and depression during pregnancy in women with epilepsy.

To assess the possibility that the occurrence of seizures or the use of antiepileptic drug (AED) therapy might have influenced the rate of occurrence of volunteered histories of patient-recognized depression during pregnancy in women with epilepsy. Analysis of data from 2039 pregnancies in the Raoul Wallenberg Australian Register of Antiepileptic Drugs in Pregnancy (APR) followed during pregnancy and to the end of the year after its end. Patient-recognized depression occurrence rates during pregnancy were a little lower rather than higher in seizure-affected than in seizure-free pregnancies (5.67% vs 6.41%), though higher in AED-treated than AED-untreated pregnancies (6.24% vs 5.26%; RR=1.185, 95% CI 0.612, 2.295). Logistic regression analysis showed that carbamazepine dosage had a statistically significant relationship with a decreasing rate of patient-recognized depression occurring during pregnancy and topiramate dosage with an increasing rate. Carbamazepine and topiramate both have established potentials for causing teratogenesis, and it is possible that replacement of carbamazepine with a less teratogenic AED, for example levetiracetam, might result in any subsequent depression that occurs in pregnancy being inappropriately attributed to the newly introduced agent.

Preexisting illness, fetal malformation, and seizure control rates in pregnant women with epilepsy

Data from 2182 pregnancies in the Australian Register of antiepileptic drugs in pregnancy that were followed to term, with 1965 followed for another year, were analyzed to ascertain whether preexisting illness influenced i. the hazard of fetal malformations, and ii. seizure control during pregnancy. Fetal malformation occurred in 74 of the 842 pregnancies associated with preexisting illness (8.8%) and in 84 of the 1340 comparator pregnancies (6.27%), Relative Risk (R.R.) = 1.402 (95% Confidence Interval (C.I.) = 1.038, 1.893). Logistic regression showed statistically significant effects of preexisting maternal drug-treated psychiatric illness, untreated psychiatric illness, and use of citalopram, carbamazepine, valproate, and topiramate in increasing hazard of fetal malformation. Preexisting nonpsychiatric illness and other antiepileptic drugs and drugs prescribed for psychiatric illness, mainly antidepressants, had no such effect. Seizures occurred during 405 of the 842 pregnancies associated with preexisting illness, and during 593 of 1340 comparison pregnancies (48.1% v 44.3%; R.R. = 1.087; 95% C.I. = 0.991, 1.192). There were no statistically significant relationships between preexisting nonpsychiatric and psychiatric illnesses separately and seizure control during pregnancy.Thus, apart from consequences of antiepileptic drug exposure, preexisting maternal psychiatric illness, in its own right, or when treated with citalopram, appears to be associated with increased hazards of fetal malformation.

Seizures in infancy in the offspring of women with epilepsy.

To assess (a) the incidence of seizures in the first year of life in infants born to mothers with epilepsy and (b) factors that might contribute to the seizure incidence. Analysis of data collected in the Australian Register of Antiepileptic Drugs in Pregnancy during and at the end of the year after pregnancy. By the end of a year following pregnancy, seizures had occurred in the progeny of 47 pregnancies (2.40%), including febrile seizures in 18 (0.92%), the latter rate being higher than the 0.40% and 0.59% rates for the same situation in the general population reported in the recent literature. Seizures in infancy were more likely in the offspring of mothers with generalized as compared with focal epilepsies (3.65% vs 1.56%; RR=2.332; P<.05) and within the generalized epilepsy mothers in those who were not seizure free during pregnancy (4.83% vs 2.89%). Seizures were also more likely in infants with foetal malformations, especially ones not discovered until after the first post-natal month. These findings may help in advising mothers with epilepsy regarding the chance of their offspring experiencing seizures in the first year of life; they also suggest the desirability of achieving maternal seizure control throughout pregnancy.

Are Antidepressant Medications Safe for Pregnant Women With Epilepsy? The Signs Point to Yes.

The Use of Antidepressant Drugs in Pregnant Women With Epilepsy: A Study From the Australian Pregnancy Register Sivathamboo N, Hitchcock A, Graham J, et al. Epilepsia. 2018;59(9):1696-1704. doi:10.1111/epi.14539Objective: To study interactions between first-trimester exposure to antidepressant drugs (ADDs) and antiepileptic drugs (AEDs) and a history of clinical depression and/or anxiety on pregnancy outcomes and seizure control in pregnant women with epilepsy (WWE). Methods: We examined data from the Australian Pregnancy Register of Antiepileptic Drugs in Pregnancy, collected from 1999 to 2016. The register is an observational, prospective database, from which this study retrospectively analyzed a cohort. Among the AED-exposed outcomes, comparisons were made among 3 exposure groups: (1) pregnancy outcomes with first-trimester exposure to ADDs, (2) outcomes with mothers diagnosed with depression and/or anxiety but who were not medicated with an ADD, and (3) those with mothers who were not diagnosed with depression and/or anxiety and were not medicating with ADD. Prevalence data were analyzed using Fisher exact test. Results: A total of 2124 pregnancy outcomes were included in the analysis; 1954 outcomes were exposed to AEDs in utero, whereas 170 were unexposed. Within the group of WWE taking AEDs, there was no significant difference in the prevalence of malformations in infants who were additionally exposed to ADDs (10.2%; 95% confidence interval [CI]: 3.9-16.6), compared to individuals in the non-ADD-medicated depression and/or anxiety group (7.7%, 95% CI: 1.2-14.2), or those without depression or anxiety (6.9%, 95% CI: 5.7-8.1; P = .45). The malformation rates in pregnancy outcomes unexposed to AEDs were also similar in the above groups (P = .27). In WWE medicated with AEDs and ADDs, the frequency of convulsive seizures (P = .78), or nonconvulsive seizures (P = .45) throughout pregnancy, did not differ across comparative groups. Significance: Comedicating with ADDs in WWE taking AEDs does not appear to confer a significant added teratogenic risk, and it does not affect seizure control.

Treatment of Juvenile Myoclonic Epilepsy in Patients of Child-Bearing Potential.

Juvenile myoclonic epilepsy (JME) is both a frequent and a very characteristic epileptic syndrome with female preponderance. Treatment of JME in women of childbearing potential must consider multiple factors such as desire for pregnancy, use of contraception, seizure control and previously used antiepileptic drugs (AEDs). Approximately 85% of cases are well controlled with valproate, which remains the reference AED in JME but is nowadays considered unsafe for the expecting mother and her fetus. The prescription of valproate is now severely restricted in women of childbearing potential but may still be considered, at the lowest possible dose and when pregnancies can be reliably planned, with temporary alternatives to valproate prescribed before fertilization. Alternatives have emerged, especially lamotrigine and levetiracetam, but also topiramate, zonisamide, and recently perampanel, but none of these AEDs can be considered fully safe in the context of pregnancy. In special settings, benzodiazepines and barbiturates may be useful. In some cases, combination therapy, especially lamotrigine and levetiracetam, may be useful or even required. However, lamotrigine may have the potential to aggravate JME, with promyoclonic effects. Carbamazepine, oxcarbazepine and phenytoin must be avoided. Valproate, levetiracetam, zonisamide, topiramate if the daily dose is ≤ 200mg and perampanel if the daily dose is ≤ 10mg do not affect combined hormonal contraception. Lamotrigine ≥ 300mg/day has been shown to decrease levonorgestrel levels by 20% but does not compromise combined hormonal contraception. Patients with JME taking oral contraceptive should be counselled on the fact that the estrogenic component can reduce concentrations of lamotrigine by over 50%, putting patients at risk of increased seizures. Pregnancy is a therapeutic challenge, and the risk/benefit ratio for the mother and fetus must be considered when choosing the appropriate drug. Lamotrigine (< 325mg daily in the European Registry of Antiepileptic Drugs in Pregnancy) and levetiracetam seem to be comparatively safer in pregnancy than other AEDs, especially topiramate and valproate. Plasma concentration of lamotrigine and levetiracetam decreases significantly during pregnancy, and dosage adjustments may be necessary. With persisting generalized tonic-clonic seizures, the combination of lamotrigine and levetiracetam offer the chance of seizure control and lesser risks of major congenital malformations. The risk of malformation increases when valproate or topiramate are included in the drug combination. In one study, the relative risk of autism and autism spectrum disorders (ASD) in children born to women with epilepsy (WWE) treated with valproate were, respectively, 5.2 for autism and 2.9 for ASD versus 2.12 for autism and 1.6 for ASD in WWE not treated with valproate. More studies are needed to assess the risk of autism with AEDs other than valproate. The current knowledge is that the risk appears to be double that in the general population. In patients with JME, valproate remains an essential and life-changing agent. The consequences of a lifetime of poorly controlled epilepsy need to be balanced against the teratogenic risks of valproate during limited times in a woman's life. The management of JME in WWE should include lifestyle interventions, with avoidance of sleep deprivation, and planned pregnancy.

Risk of Cleft Lip and/or Palate Associated With Antiepileptic Drugs: Postmarketing Safety Signal Detection and Evaluation of Information Presented to Prescribers and Patients

The aim was to analyze safety data associated with the maternal use of antiepileptic drugs in pregnancy and to assess the risk of cleft lip and/or palate (CL/P) as an outcome in the neonate. A parallel objective was to assess the completeness of the safety information concerning pregnancy exposures in the Summary of Product Characteristics (SmPCs) and the Patient Information (PI) in the USA and the UK. We analyzed individual case safety reports of CL/P associated with antiepileptic drugs in the FDA Adverse Event Reporting System. For the antiepileptic drugs with signals (EB05 ≥ 2), we reviewed Drug Analysis Prints for CL/P cases in the UK Medicines and Healthcare products Regulatory Agency (MHRA). We performed descriptive analyses of relevant SmPCs and PIs in the UK and the USA using a checklist of recommendations collected from the literature. In total 817 CL/P reports were identified for 12 antiepileptic drugs in the FDA Adverse Event Reporting System. Ten of the 12 antiepileptic drugs were associated with 156 CL/P cases in the MHRA Sentinel. Safety information concerning pregnancy was found to be more comprehensive in UK SmPCs than in the US equivalents. There is statistical disproportionality in individual case safety reports indicative of an increased risk of CL/P with 12 antiepileptic drugs studied. More studies are required to explore the association between in utero exposure to antiepileptic drugs and the risk of CL/P. There are inconsistencies between the UK and US safety labels. CL/P associated with antiepileptic drugs is an important topic and requires providing inclusive, unbiased, up-to-date information to prescribers and women of childbearing age.

513: Obstetric outcomes for women receiving newer generation antiepileptic drugs: retrospective cohort study using claims database

Women with epilepsy are at increased risk for adverse pregnancy outcomes. Since the 1990s, over 11 new antiepileptic drugs (AEDs) have been introduced. We aimed to describe the use of newer AEDs in pregnancy and differences in rates of obstetric outcomes. From the Truven Health MarketScan® Commercial Claims and Encounters Database (years 2011-14), we identified women who had a delivery admission, outpatient pharmacy dispenses for newer generation AEDs (Table) and an indication of epilepsy based on diagnosis codes during the 12 months prior to delivery. Obstetric outcomes included preterm birth, cesarean delivery, postpartum hemorrhage, placental abruption, hypertensive disorders of pregnancy, preterm labor, and severe maternal morbidity (SMM). We described the prevalence of the use of newer AEDs and rates of obstetric outcomes and absolute risk difference compared to women without a diagnosis of epilepsy (Table). In the cohort analyzed (n=1,028,125), the prevalence of epilepsy was 0.44% (n=4,528). Overall, 55% (n=2,508) received any of these AEDs during pregnancy, the most common of which were lamotrigine (49.8%) and levetiracetam (42.5%). Compared to the non-epileptic control group, women on AEDs showed significant increases in the absolute risk of cesarean delivery (5.0%), preeclampsia (0.7%), severe preeclampsia/eclampsia (0.9%) and SMM (1.6%). AEDs with the highest increases in absolute risk were topiramate (6.7%) for cesarean delivery, lamotrigine for pre-eclampsia (1.1%), and lacosamide for severe preeclampsia/eclampsia (8.4%) and SMM (9.3%). Of the 2,508 women, 414 (16.5%) received more than one AED during pregnancy. Compared to women receiving a single AED, those who received multiple AEDs had higher absolute risks of all outcomes except postpartum hemorrhage (Table). Compared to non-epileptic women, women on newer generation AEDs demonstrated an increased absolute risk for cesarean delivery, preeclampsia, severe preeclampsia/eclampsia and severe maternal morbidity. Women receiving multiple medications demonstrated the highest increase in absolute risk for adverse outcomes, similar to findings in older AEDs, possibly also reflecting a more complicated and difficult disease state.

The use of antidepressant drugs in pregnant women with epilepsy: A study from the Australian Pregnancy Register.

To study interactions between first-trimester exposure to antidepressant drugs (ADDs) and antiepileptic drugs (AEDs), and a history of clinical depression and/or anxiety, on pregnancy outcomes and seizure control in pregnant women with epilepsy (WWE). We examined data from the Australian Pregnancy Register of Antiepileptic Drugs in Pregnancy, collected from 1999 to 2016. The register is an observational, prospective database, from which this study retrospectively analyzed a cohort. Among the AED-exposed outcomes, comparisons were made among 3 exposure groups: (1) pregnancy outcomes with first-trimester exposure to ADDs; (2) outcomes with mothers diagnosed with depression and/or anxiety but who were not medicated with an ADD; and (3) those with mothers who were not diagnosed with depression and/or anxiety and were not medicating with ADD. Prevalence data was analyzed using Fisher's exact test. A total of 2124 pregnancy outcomes were included in the analysis; 1954 outcomes were exposed to AEDs in utero, whereas 170 were unexposed. Within the group of WWE taking AEDs, there was no significant difference in the prevalence of malformations in infants who were additionally exposed to ADDs (10.2%, 95% confidence interval [CI] 3.9-16.6), compared to individuals in the non-ADD-medicated depression and/or anxiety group (7.7%, 95% CI 1.2-14.2), or those without depression or anxiety (6.9%, 95% CI 5.7-8.1; P=0.45). The malformation rates in pregnancy outcomes unexposed to AEDs were also similar in the above groups (P=0.27). In WWE medicated with AEDs and ADDs, the frequency of convulsive seizures (P=0.78), or nonconvulsive seizures (P=0.45) throughout pregnancy, did not differ across comparative groups. Co-medicating with ADDs in WWE taking AEDs does not appear to confer a significant added teratogenic risk, and it does not affect seizure control.

Antiepileptic Drugs in Pregnancy—Quick Decisions With Long-term Consequences

Antiepileptic Drugs in Pregnancy—Quick Decisions With Long-term Consequences

Anti-epileptic drug exposure and risk of foetal death in utero.

To clarify whether anti-epileptic drug exposure during pregnancy is associated with an increased risk of intrauterine foetal death. Analysis of data from 2064 pregnancies with known outcomes included in the Australian Register of Antiepileptic Drugs in Pregnancy, 170 of the pregnancies being unexposed to the drugs in at least the first half of pregnancy. The relative risk (6.46; 95% C.I. 0.90, 46.22) of intrauterine death appeared higher, though not statistically significantly higher, in drug-exposed pregnancies compared with unexposed ones (3.44% vs 0.59%). There was no statistically significantly increased hazard associated with AED polytherapy as compared with monotherapy. Logistic regression analysis showed a statistically significantly increased and dose-related hazard of intrauterine death in relation to carbamazepine exposure. Intrauterine exposure to anti-epileptic drugs, particularly carbamazepine, may be associated with an increased risk of foetal death during pregnancy.

Preferences of Pregnant Women for Outcomes Related to Epilepsy and the Use of Antiepileptic Medications in Pregnancy [18N

INTRODUCTION: Women with epilepsy are at risk of higher seizure-frequency in pregnancy and fetal malformations from the use of antiepileptic drugs (AEDs). The trade-offs women are willing to make, to optimize pregnancy outcomes have not been determined. This study elicits preferences of pregnant women with and without epilepsy, for maternal and fetal health states related to epilepsy and the use of AEDs in pregnancy with a view to informing practice and research. METHODS: Cross-sectional study on pregnant women that had epilepsy or another chronic medical disorder requiring medications during pregnancy. Study participants were presented with seven vignettes related to epilepsy and the use of AEDs in pregnancy and asked to assign them values on a visual analogue scale, by the standard gamble and time trade-off methods. Utility values were presented on a scale of 0-100. RESULTS: 52 pregnant women completed the interviews. The median age was 33 (29.5-35) years and the median gestational age was 30 weeks. The epileptic and non-epileptic groups had identical demographic characteristics. Utility values for combined maternal-fetal health states related to epilepsy and the use of AEDs was obtained by three methods, from women with and without epilepsy. There were no differences in utility values obtained between groups regardless of the method used. CONCLUSION: This study provides utility values for combined maternal-fetal health states related to epilepsy and the use of AEDs for use in decision analysis studies and suggests that these preferences could be obtained from pregnant women with any chronic medical disorder taking medications during pregnancy.