Maternofetal carnitine transport through the placenta is the main route of fetal carnitine uptake. Decreased free carnitine levels discovered by newborn screening has identified many asymptomatic adult women with systemic primary carnitine deficiency (PCD). Here, we presented amplitude integrated electroencephalogram (aEEG) and magnetic resonance imaging (MRI) findings from a neonate with epilepsy whose mother was carnitine deficient. A one-day-old female newborn was admitted after experiencing seizures for half a day; status epilepticus was found on the continuous normal voltage background pattern with immature sleep-wake cycling during aEEG monitoring. On T1-weighted, T2-weighted, FLAIR, and DWI head MRI, there were various degrees of hyperintense signals and diffusion restrictions in the deep white matter of the right hemisphere. Tandem mass spectrometry discovered carnitine deficiency on the second day, which elevated to normal by the 9th day before L-carnitine supplementation was started. The patient was treated with phenobarbital after admission. No further seizures were noted by day 5. It was confirmed that the patient's mother had a low level of serum-free carnitine. Gene analyses revealed that the newborn had heterozygote mutations on c.1400C > G of the SLC22A5 gene, and her mother had homozygous mutations on c.1400C > G. The patient had a good outcome at the 8-month follow up. Maternal carnitine deficiency that occurs during the perinatal period may manifest as secondary epilepsy with cerebral injury in neonates. The short-term neurodevelopmental outcomes were good. Early diagnosis of asymptomatic PCD in female patients can provide guidance for future pregnancies.

We review data on the comparative teratogenicity of antiepileptic drugs (AEDs), focusing on major congenital malformations (MCMs), intrauterine growth restriction, impaired cognitive development, and behavioral adverse effects following prenatal exposure. Prospective registries and meta-analyses have better defined the risk of MCMs in offspring exposed to individual AEDs at different dose levels. Valproate is the drug with the highest risk, whereas prevalence of MCMs is lowest with lamotrigine, levetiracetam, and oxcarbazepine. For valproate, phenobarbital, phenytoin, carbamazepine, and lamotrigine, the risk of MCMs is dose-dependent. Prenatal exposure to valproate has also been confirmed to cause an increased risk of cognitive impairments and autistic traits. In a population-based study, the risk of AED-induced autistic traits was attenuated by periconceptional folate supplementation. The risk of adverse fetal effects differs in relation to the type of AED and for some AEDs also the daily dose. Although for MCMs the risk is primarily associated with the first trimester of gestation, influences on cognitive and behavioral development could extend throughout pregnancy. Available information now permits a more rational AED selection in women of childbearing potential, and evidence-based counseling on optimization of AED treatment before conception.

This review of literature is devoted to contemporary issues of antiepileptic therapy in pregnancy, with identifying the most effective drug according to publications from 2006 to 2016 (PUBMED, MEDline, The Cochrane Lb.). The review presents the current published data on the incidence of seizures in pregnant women, specificity of therapy with antiepileptic drugs (AEDs), frequency of fetal malformations in pregnant women taking AEDs regularly and their dependence on the frequency, dosage and nature of therapy. The authors studied and analyzed the literature on antiepileptic therapy with AED for the last ten years and selected AED with the least teratogenic effect and less side-effects. Lamotrigine, phenytoin, carbamazepine, valproic acid, phenobarbital were studied. In addition to classic AEDs, new AEDs (vigabatrin, gabapentin, topiramate, tiagabine, oxcarbazepine, levetiracetam, pregabalin) were investigated. Over the past decade, the use of new-generation AEDs has increased. It has been found that the risk of birth defects in children is associated with high doses of drugs and polytherapy compared to monotherapy. New data of recent studies showed the effect of psychotropic drugs on the fetus allowing to assess the 'risk/benefit' ratio and develop recommendations on rational pharmacotherapy of epilepsy in pregnancy. Обзор литературы посвящен современным вопросам противоэпилептической терапии беременных различными препаратами с выявлением наиболее эффективного из них по данным научных публикаций с 2006 по 2016 г. (PubMed, Medline, The Cochrane Lb.). Представлены современные данные литературы по встречаемости судорожного синдрома у беременных, особенностям терапии противоэпилептическими препаратами (ПЭП), по частоте внутриутробных пороков развития среди беременных, регулярно принимавших ПЭП, и их зависимость от частоты, дозировки и характера проводимой терапии. Изучены и проанализированы данные литературы за последние 10 лет по противоэпилептической терапии различными ПЭП с определением препаратов с наименьшим тератогенным эффектом и с меньшим развитием побочных эффектов. Были изучены такие ПЭП, как ламотриджин, фенитоин, карбамазепин, вальпроевая кислота, фенобарбитал. Помимо классических ПЭП, авторами были исследованы новые препараты (вигабатрин, габапентин, топирамат, тиагабин, окскарбазепин, леветирацетам, прегабалин). За последнее 10-летие увеличилось использование ПЭП нового поколения. При этом было установлено, что риск развития врожденных пороков у детей чаще наблюдается при применении высоких доз препаратов и политерапии, чем при монотерапии. В исследованиях последних лет выявлены новые данные о влиянии психотропных препаратов на плод, позволяющие оценивать их соотношение 'польза/риск' и разрабатывать рекомендации по рациональной фармакотерапии эпилепсии у беременных.

We present an atypical association of SCN2A epileptic encephalopathy with severe cortical dysplasia. SCN2A mutations are associated with epileptic syndromes from benign to extremely severe in absence of such macroscopic brain findings. Prenatal MRI (Magnetic Resonance Imaging) in a 32 weeks fetus, with US (Ultrasonography) diagnosis of isolated ventriculomegaly showed CNS (Central Nervous System) dysplasia characterized by lack of differentiation between cortical and subcortical layers, pachygyria and corpus callosum dysgenesis. Postnatal MRI confirmed the prenatal findings. On day 6 the baby presented a focal status epilepticus, partially controlled by phenobarbital, phenytoin, and levetiracetam. After three weeks a moderate improvement in seizure control has been achieved with carbamazepine. Exome sequencing detected a de novo heterozygous mutation in the SCN2A gene, encoding the αII-subunit of a sodium channel. The patient findings expand the phenotype spectrum of SCN2A mutations to epileptic encephalopathies with macroscopic brain developmental features.

Antiepileptic drugs (AEDs) are among the most common teratogenic drugs prescribed to women of childbearing age. AEDs can induce both anatomical (malformations) and behavioral (cognitive/behavioral deficits) teratogenicity. Only in the last decade have we begun to truly discriminate differential AED developmental effects. Fetal valproate exposure carries a special risk for both anatomical and behavioral teratogenic abnormalities, but the mechanisms and reasons for individual variability are unknown. Intermediate anatomical risks exist for phenobarbital and topiramate. Several AEDs (e.g., lamotrigine and levetiracetam) appear to possess low risks for both anatomical and behavioral teratogenesis. Despite advances in the past decade, our knowledge of the teratogenic risks for most AEDs and the underlying mechanisms remain inadequate. Further, the long-term effects of AEDs in neonates and older children remain uncertain. The pace of progress is slow given the lifelong consequences of diminished developmental outcomes, exposing children unnecessarily to potential adverse effects. It is imperative that new approaches be employed to determine risks more expediently. Our recommendations include a national reporting system for congenital malformations, federal funding of the North American AED Pregnancy Registry, routine meta-analyses of cohort studies to detect teratogenic signals, monitoring of AED prescription practices for women, routine preclinical testing of all new AEDs for neurodevelopmental effects, more specific Food and Drug Administration requirements to establish differential AED cognitive effects in children, and improved funding of basic and clinical research to fully delineate risks and underlying mechanisms for AED-induced anatomical and behavioral teratogenesis.