Comparative Risk of Major Congenital Malformations With 8 Different Antiepileptic Drugs: A Prospective Cohort Study of the EURAP Registry

Vossler, David G.

doi:10.1177/1535759719835353

Cited by 27 publications

(32 citation statements)

References 12 publications

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“…In 2019 EURAP reported 7335 pregnancies on monotherapy with eight ASMs). 42 Kerala and the Australian Registry also contribute 40–80% of their pregnancies to EURAP. 43 …”

Section: Management Of Epilepsy During Pregnancy and Anti-seizure Med...mentioning

confidence: 99%

Treatment and care of women with epilepsy before, during, and after pregnancy: a practical guide

Nucera

Brigo

Trinka

et al. 2022

Ther Adv Neurol Disord

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Women with epilepsy (WWE) wishing for a child represent a highly relevant subgroup of epilepsy patients. The treating epileptologist needs to delineate the epilepsy syndrome and choose the appropriate anti-seizure medication (ASM) considering the main goal of seizure freedom, teratogenic risks, changes in drug metabolism during pregnancy and postpartum, demanding for up-titration during and down-titration after pregnancy. Folic acid or vitamin K supplements and breastfeeding are also discussed in this review. Lamotrigine and levetiracetam have the lowest teratogenic potential. Data on teratogenic risks are also favorable for oxcarbazepine, whereas topiramate tends to have an unfavorable profile. Valproate needs special emphasis. It is most effective in generalized seizures but should be avoided whenever possible due to its teratogenic effects and the negative impact on neuropsychological development of in utero-exposed children. Valproate still has its justification in patients not achieving seizure freedom with other ASMs or if a woman decides to or cannot become pregnant for any reason. When valproate is the most appropriate treatment option, the patient and caregiver must be fully informed of the risks associated with its use during pregnancies. Folate supplementation is recommended to reduce the risk of major congenital malformations. However, there is insufficient information to address the optimal dose and it is unclear whether higher doses offer greater protection. There is currently no general recommendation for a peripartum vitamin K prophylaxis. During pregnancy most ASMs (e.g. lamotrigine, oxcarbazepine, and levetiracetam) need to be increased to compensate for the decline in serum levels; exceptions are valproate and carbamazepine. Postpartum, baseline levels are reached relatively fast, and down-titration is performed empirically. Many ASMs in monotherapy are (moderately) safe for breastfeeding and women should be encouraged to do so. This review provides a practically oriented overview of the complex management of WWE before, during, and after pregnancy.

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“…In 2019 EURAP reported 7335 pregnancies on monotherapy with eight ASMs). 42 Kerala and the Australian Registry also contribute 40–80% of their pregnancies to EURAP. 43 …”

Section: Management Of Epilepsy During Pregnancy and Anti-seizure Med...mentioning

confidence: 99%

Treatment and care of women with epilepsy before, during, and after pregnancy: a practical guide

Nucera

Brigo

Trinka

et al. 2022

Ther Adv Neurol Disord

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“…Other important defects include those of cardiovascular (ventricular septal defect (VSD), patent ductus arteriosus (PDA), aortic coarctation), respiratory (tracheomalacia), and urogenital systems (inguinal hernia, hypospadias, cryptorchidism, incomplete fusion of the Müllerian duct). The incidence of meningomyelocele, especially lumbar or lumbosacral, is reported to be 1-2% with in utero fetal exposure during the first trimester [30,31]. Developmental anomalies and autism are other teratogenic effects of VPA described in the literature.…”

Section: Valproic Acidmentioning

confidence: 99%

The Pathogenesis of Congenital Anomalies: Roles of Teratogens and Infections

Demirtas¹

2021

Congenital Anomalies in Newborn Infants - Clinical and Etiopathological Perspectives

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Congenital anomalies present with significant financial, social, and moral issues and questions to the family and society and are difficult to rehabilitate. In utero exposure to teratogenic agents and infection are the two most important causes of nongenetic acquired anomalies presenting at birth. Teratogens such as drugs, adverse maternal conditions, and toxins are environmental factors that cause permanent structural or functional malformations or death of the embryo or fetus. Teratogens may cause significant congenital anomalies if encountered during the organogenesis period of 3-8 weeks of fetal life, which is the stage of tissues and organs formation, whereas minor morphological and functional disorders may occur with exposure during the fetal period of first 2 weeks. TORCH group infections (toxoplasmosis, others, rubella, cytomegalovirus, and herpes) are the most serious infectious diseases during pregnancy due to the severity of possible embryofetal lesions. With expanding scientific knowledge and clinical experience about the association of these toxins and infections with significant, at times crippling congenital anomalies, the avoidance of exposure to pregnant mothers has become the most important part of their prevention and management.

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“…Эти закономерности прослеживаются при анализе большинства регистров беременности. Например, в исследовании D. G. Vossler (2019), сравнивающем тератогенный эффект 8 АЭП по данным регистра EURAP, охватывающего 42 страны, частота пороков развития для ламотриджина и леветирацетама остается наименьшей и составляет 74 (2,9 %) случая из 2514 случаев беременности для ламотриджина, 10 (3,0 %) случаев из 333 для окскарбазепина и 17 (2,8 %) случаев из 599 для леветирацетама [54]. Хотелось бы обратить внимание на то, что число случаев беременности на фоне приеме ламотриджина значительно превышает число наблюдений для других новых АЭП.…”

Section: Ch I Ld Neurology R U S S I a N J O U R N A L O Funclassified

Efficacy and tolerability of Seizar (lamotrigine) in the treatment of epilepsy (experience of Svt. Luka’s Institute of Child Neurology and Epilepsy)

Пылаева¹,

Мухин²

2020

Rus. ž. det. nevrol.

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Background. We have accumulated extensive experience in the use of lamotrigine in patients with epilepsy; its mechanism of action, effectiveness, safety, and tolerability are well known. The results of numerous studies indicate its high efficacy and potentially better tolerability compared to other drugs in the treatment of a wide range of epilepsy forms and epileptic syndromes (focal and generalized seizures). These characteristics of lamotrigine determined its priority administration as initial or alternative monotherapy in women with epilepsy. Objective: to review efficacy and tolerability of Seizar in patients with various forms of epilepsy based on long-term experience of using this drug in our center. Materials and methods. We analyzed therapeutic effects of Seizar in 22 patients aged between 3 and 34 years (mean age 15.3 years) treated in Svt. Luka’s Institute of Child Neurology and Epilepsy. The sample included 8 adults and 14 children (under 18 years of age), including 6 children aged from 3 to 12 years. Ten patients were male and twelve patients were female. Study participants were diagnosed with the following forms of epilepsy: idiopathic (genetic) generalized epilepsy (n = 9), idiopathic (genetic) focal epilepsy (n = 2), focal epilepsy of unknown etiology (n = 1), structural and probably structural focal epilepsy (n = 4), genetic and probably genetic epileptic encephalopathies (n = 6). Seizar was used as monotherapy in 9 patients and as an additional drug in 13 patients. Children aged 3 to 12 years received Seizar only as an additional drug in polytherapy (n = 6); patients aged between 12 and 18 years received it either as monotherapy (n = 4) or in addition to other treatments (n = 4). Five adults received Seizar alone, whereas 3 adults received it as a part of polytherapy. In total, 9 participants received monotherapy with Seizar and 13 participants received Seizar with other treatments. In two patients, combination therapy was successfully changed to monotherapy with Seizar (they are currently receiving it as monotherapy). Seizar dose varied between 75 and 400 mg per day given in 1–2 portions. Importantly, prolonged action of Seizar and convenient dose of 200 mg per tablet allows its administration once a day. Currently, 4 patients (one 15-year-old girl and 3 adults) are receiving Seizar once a day (3 of them at bedtime and one of them in the morning). The follow-up period was between 4 months and 5 years. Results. Therapeutic remission with Seizar was achieved in 7 out of 22 patients (31.8 %); 10 patients (45.5 %) demonstrated at least 50 % reduction in seizure frequency; 5 patients (22,7 %) had no effect. None of the participants had seizure aggravation. Seizar was ceased in 2 patients (9 %) due to its inefficacy. Therefore, therapeutic effect (clinical remission or more than 50 % reduction in seizure frequency) was achieved in 17 out of 22 patients (77 %), which is a very good result considering the fact that all participants had severe forms of epilepsy. Seizar was most effective in patients with idiopathic epilepsy (≥50 % reduction in seizure frequency/clinical remission was observed in 9 out 11 patients (81 %), including 5 patients receiving Seizar as monotherapy) and structural focal epilepsy or focal epilepsy of unknown etiology (≥50 % reduction in seizure frequency/clinical remission was observed in 4 out of 5 patients (80 %)). Positive effect was achieved in 4 out of 6 participants (66 %) with epileptic encephalopathies; this group included patients with extremely severe forms of epilepsy and resistance to many antiepileptic drugs (AED). Seizar was well tolerated by patients: 72.8 % of them had no side effect and only 5 patients (22.7 %) had transient disorders of the central nervous system and gastrointestinal tract (nausea, loss of appetite) that did not require discontinuation of the drug. Only one patient (4.5 %) required its cessation. In 4 female patients of reproductive age, Seizar was used to optimize therapy as a part of preparation for pregnancy. High efficacy and good tolerability of Seizar are confirmed by patients’ adherence to treatment: 19 of 22 patients included into the study (86 %) still continue to receive Seizar (the duration of follow-up period varies between 4 months and 5 years). Only 3 participants required drug discontinuation due to skin rash (n = 1; 4.5 %) and low efficacy (n = 2; 9 %). Conclusions. Over the past decades, clinicians have accumulated evidence of good safety and tolerability of lamotrigine, including such aspects as its positive effect on cognitive functions, behavior, mood (including that in children), and particularly good safety profile in women of reproductive age. Lamotrigine and levetiracetam are currently considered the safest AED for women of reproductive age in terms of their impact on the neuroendocrine system of women, fertility, and potential teratogenic effect. The number of pregnancies among women receiving lamotrigine is significantly higher than that among women receiving other AED. Thus, the safety of lamotrigine during pregnancy (as well as other aspects of its safety and tolerability) are studied much better compared to other AED. It is very important that lamotrigine is considered a safe drug.

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Comparative Risk of Major Congenital Malformations With 8 Different Antiepileptic Drugs: A Prospective Cohort Study of the EURAP Registry

Cited by 27 publications

References 12 publications

Treatment and care of women with epilepsy before, during, and after pregnancy: a practical guide

Treatment and care of women with epilepsy before, during, and after pregnancy: a practical guide

The Pathogenesis of Congenital Anomalies: Roles of Teratogens and Infections

Efficacy and tolerability of Seizar (lamotrigine) in the treatment of epilepsy (experience of Svt. Luka’s Institute of Child Neurology and Epilepsy)

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