The fetal valproate syndrome

DiLiberti, John H.; Farndon, Peter; Dennis, N R; Curry, Cynthia J.

doi:10.1002/ajmg.1320190308

Cited by 357 publications

(162 citation statements)

References 12 publications

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“…Developmental delay is one of the main features of the fetal valproate syndrome [54,[65][66][67], which is otherwise characterized by a typical pattern of minor anomalies: trigonocephaly, bifrontal narrowing with indentation of the outer orbital ridge, medial deficiency of eyebrows, long shallow philtrum with long and thin upper lip, and broad or flat nasal bridge. Major malformations, especially neural tube and limb defects, may also occur.…”

Section: Valproatementioning

confidence: 99%

Cognitive/behavioral teratogenetic effects of antiepileptic drugs

Meador

Baker

Cohen

et al. 2007

Epilepsy & Behavior

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The majority of children of mothers with epilepsy are normal, but they are at increased risk for developmental delay. Antiepileptic drugs (AEDs) appear to play a role. Our current knowledge is reviewed, including research design issues and recommendations for future research. In animals, exposure of the immature brain to some AEDs can produce widespread neuronal apoptosis and behavioral deficits. The risks of AEDs in humans are less clear, but recent studies raise concerns, especially for valproate. There is a critical need for well-designed systematic research to improve our understanding of AED effects on the fetal brain. KeywordsAntiepileptic drugs; Anticonvulsant drugs; Pregnancy; Teratogenesis; Development; Cognition; Behavior Animal studies on behavioral effects of in utero AED exposureAnimal studies have demonstrated that in utero antiepileptic drug (AED) exposure can produce behavioral as well as anatomical defects, which can occur at dosages lower than those required to produce somatic malformations [1,2]. Gestational or neonatal exposure to benzodiazepines can affect brain chemistry and behavior causing hyperactivity or learning deficits [3,4]. Despite the common use of carbamazepine in humans, very few neurobehavioral studies in animals have been conducted with this AED. In utero carbamazepine exposure did not produce hyperexcitability in primates [5]. Perinatal phenobarbital exposure in rats reduces brain weight [6]. Mice exposed prenatally to phenobarbital have neuronal deficits, reduced brain weight, and impaired development of reflexes, open-field activity, schedule-controlled behavior, spatial learning, and cate-cholamine brain levels [7][8][9][10][11][12]. Gestational or neonatal exposure to phenytoin reduces brain weight [13,14], alters neuronal membranes in the hippocampus [15], delays neurodevelopment [16], and impairs spatial learning and motor coordination [17][18][19][20][21][22][23][24][25]. Hyperactivity has been observed in rats and primates following prenatal exposure to phenytoin [5,23,25]. Gestational primidone in rats produces learning deficits and reduces open-field activity [26]. In utero valproate exposure can alter neuronal membranes [27], decrease brain weight in mice [28], and result in adverse neurobehavioral effects [29,30].

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Section: Valproatementioning

confidence: 99%

Cognitive/behavioral teratogenetic effects of antiepileptic drugs

Meador

Baker

Cohen

et al. 2007

Epilepsy & Behavior

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“…Although VPA is well tolerated by patients, it can induce birth defects such as neural tube closure and other malformations, if administered during early pregnancy. 7,8 The mechanism responsible for such defects is at yet unclear. 9 Recently, VPA was demonstrated to inhibit corepressorassociated HDACs, acting on class I more efficiently than class II enzymes at therapeutically relevant concentrations mimicking the prototypical histone deacetylase inhibitor, tricostatine.…”

Section: Introductionmentioning

confidence: 99%

Modulation of pro- and anti-apoptotic factors in human melanoma cells exposed to histone deacetylase inhibitors

et al. 2004

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“…optic nerve hypoplasia (Hoyt & Billson 1978), cystic maculae, retinoschisis and Bergmeisters papillae (Wilson et al 1978) as well as anophthalmus, microphthalmus, iris and optic nerve coloboma, persistent hyperplastic primary vitreous (Hampton & Krepostman 1981;Bartoshesky et al 1982;Sutcliffe et al 1998), strabismus, epicanthal folds, ptosis and hypertelorism (Hanson & Smith 1975;Ornoy & Cohen 1996) and nystagmus (DiLiberti et al 1984).…”

mentioning

confidence: 99%

Visual and ocular outcome in children after prenatal exposure to antiepileptic drugs

Fahnehjelm

Wide

Ygge

et al. 1999

Acta Ophthalmologica Scandinavica

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ABSTRACT.Purpose: To prospectively study the incidence of structural and/or functional ophthalmological abnormalities in the offspring to an unselected population of women with epilepsy, subjected to a well controlled antiepileptic drug (AED) treatment during pregnancy. Methods: Forty-three children prenatally exposed to antiepileptic drugs and 47 controls were included. Blinded ophthalmological examinations including fundus photography were performed at a median age of 7 years and 4 months. Results: No major eye anomalies were found except in one child in the exposed group who had nystagmus and low vision. The visual acuity was lower in the eye with lowest acuity among the exposed children (p∞0.05). No other significant difference was found between the two groups. Conclusion:The results suggest that a well-controlled treatment with AEDs, preferably monotherapy, during pregnancy does not have any major adverse effects on the development of the eye and ophthalmological functions.

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The fetal valproate syndrome

Cited by 357 publications

References 12 publications

Cognitive/behavioral teratogenetic effects of antiepileptic drugs

Cognitive/behavioral teratogenetic effects of antiepileptic drugs

Modulation of pro- and anti-apoptotic factors in human melanoma cells exposed to histone deacetylase inhibitors

Visual and ocular outcome in children after prenatal exposure to antiepileptic drugs

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