Maternal Valproic Acid and Congenital Neural Tube Defects

Robert, Elisabeth; Guibaud, P

doi:10.1016/s0140-6736(82)90908-4

Cited by 495 publications

(193 citation statements)

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“…The HDAC Inhibitor Trichostatin A Mimics VPA Effects on Embryogenesis-VPA is highly teratogenic in humans, causing spina bifida aperta and other neural tube closure defects in 1-2% of offspring of women taking VPA during the first trimester of pregnancy (5). Similarly, VPA causes neural tube defects in rodents, and this has served as a commonly studied model of teratogenesis.…”

Section: Vpa Activates Tcf/lef-dependent Transcription and Synergizesmentioning

confidence: 99%

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Histone Deacetylase Is a Direct Target of Valproic Acid, a Potent Anticonvulsant, Mood Stabilizer, and Teratogen

Phiel¹,

Zhang²,

Huang³

et al. 2001

Journal of Biological Chemistry

1,579

1,194

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Valproic acid is widely used to treat epilepsy and bipolar disorder and is also a potent teratogen, but its mechanisms of action in any of these settings are unknown. We report that valproic acid activates Wntdependent gene expression, similar to lithium, the mainstay of therapy for bipolar disorder. Valproic acid, however, acts through a distinct pathway that involves direct inhibition of histone deacetylase (IC 50 for HDAC1 ‫؍‬ 0.4 mM). At therapeutic levels, valproic acid mimics the histone deacetylase inhibitor trichostatin A, causing hyperacetylation of histones in cultured cells. Valproic acid, like trichostatin A, also activates transcription from diverse exogenous and endogenous promoters. Furthermore, valproic acid and trichostatin A have remarkably similar teratogenic effects in vertebrate embryos, while non-teratogenic analogues of valproic acid do not inhibit histone deacetylase and do not activate transcription. Based on these observations, we propose that inhibition of histone deacetylase provides a mechanism for valproic acid-induced birth defects and could also explain the efficacy of valproic acid in the treatment of bipolar disorder.

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Section: Vpa Activates Tcf/lef-dependent Transcription and Synergizesmentioning

confidence: 99%

“…VPA is a potent teratogen in humans (5) and is widely studied as a model teratogen in rodents. Although the target of VPA in this setting is unknown, strict structural requirements have been defined for the teratogenic activity of VPA and VPA-related compounds.…”

mentioning

confidence: 99%

Histone Deacetylase Is a Direct Target of Valproic Acid, a Potent Anticonvulsant, Mood Stabilizer, and Teratogen

Phiel¹,

Zhang²,

Huang³

et al. 2001

Journal of Biological Chemistry

1,579

1,194

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“…The natural-occurring folates consist o f a large group o f derivatives derived from the reduc tion and addition to the basic structure. Folates are available in part as small molecules with one to three 40 61 (1995) [39][40][41][42][43][44][45][46][47][48] The stored THF-polyglutamates can be degraded to THF-monoglutamates by intracellular conjugase and released into the circulation. 5-methyl-THF-monoglutamate is the predominant form o f folate in serum and in many tissues.…”

Section: L Structurementioning

confidence: 99%

“…Antiepileptic drugs such as phéno barbital, phenytoin and primidone can reduce folate lev els by inhibiting intestinal absorption, or by increasing folate turn-over due to induction of the cytochrome P-450 glucuronyl transferase enzymes [45,46]. The mater nal use o f valproic acid and carbamazepine is considered to increase the risk of spina bifida in particular [47,48], For both antiepileptic drugs, no strong evidence is avail able for the presence of abnormally low serum folate lev els, but several studies report some form of interference with folate metabolism [49,50]. Recently, in mice, it has been demonstrated that valproic acid interferes with the conversion o f THF into 5-formyl-THF, which is possibly due to inhibition of the enzyme glutamate formyltransferase, through which the teratogenicity of val proic acid may be explained by an altered folate metabolism [49],…”

Section: Rp Sieegers-theunissen/ European Journal O F Obstetrics and mentioning

confidence: 99%

Folate metabolism and neural tube defects: a review

Steegers‐Theunissen¹

1995

European Journal of Obstetrics & Gynecology and Reproductiv

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iThe importance o f folate in norm al fetal developm ent and wellbeing has been recognized only during the past three decades and knowledge concerned is still far from complete. In m an, folate acts as a substrate in the transfer of one-carbon moieties and thereby, plays an essential role in the synthesis o f several am ino acids such as m ethionine and nucleic acids. Consequently, folate require ments are related to the am ount of tissue growth. Epidemiological, clinical and teratological research showed that this B-vitamin is particularly involved in the prevention and pathogenesis o f neural tube defects. Therefore, in this review the metabolism o f folate has been outlined. Furtherm ore, the characteristics of the various genically determ ined folate 'deficiencies5 as well as a possible biochemical explanation o f the relationship between folate and neural tube defects are being discussed. Finally, the new recommen dations launched in N ovem ber 1993 by the D utch H ealth Council as well as the Food and N utrition Council with regard to folate supplementation in the prevention o f neural tube defects are presented.

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“…The teratogenic potential of valproate was first highlighted in the early 1980s. 1 Since then, a variety of congenital malformations, particularly neural tube defects, have been reported in children exposed to valproate in utero. The incidence of neural tube defects is estimated to be around 1-2% of live births, with rates of spina bifida up to 10-20 times those seen in the general population.…”

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confidence: 99%

Improving adherence to NICE guidance for bipolar illness: valproate use in women of childbearing potential

Mace

Taylor

2011

Psychiatrist

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Aims and methodTo assess the impact in the South London and Maudsley NHS Foundation Trust of a 20-month quality improvement programme on adherence with National Institute for Health and Clinical Excellence (NICE) recommendations for the use of valproate for bipolar illness in women of childbearing potential.ResultsSignificant improvement was noted between baseline and final audit in rates of information provision (10% v. 63%, P < 0.0001), contraceptive use (15% v. 38%, P = 0.0003) and folate prescription (3% v. 35%, P < 0.0001).Clinical implicationsAdherence to guidance can be usefully improved by a sustained intervention programme.

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Maternal Valproic Acid and Congenital Neural Tube Defects

Cited by 495 publications

References 1 publication

Histone Deacetylase Is a Direct Target of Valproic Acid, a Potent Anticonvulsant, Mood Stabilizer, and Teratogen

Histone Deacetylase Is a Direct Target of Valproic Acid, a Potent Anticonvulsant, Mood Stabilizer, and Teratogen

Folate metabolism and neural tube defects: a review

Improving adherence to NICE guidance for bipolar illness: valproate use in women of childbearing potential

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