Increased rate of major malformations in offspring exposed to valproate during pregnancy

Wyszynski, Diego F.; Nambisan, M.; Surve, Talib Y.; Alsdorf, Rachel; Smith, C. R.; Holmes, Lewis B.

doi:10.1212/01.wnl.0000154516.43630.c5

Cited by 369 publications

(217 citation statements)

References 42 publications

(37 reference statements)

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“…This demonstrates a highly specific developmental function (Haberland et al, 2009). Consequently, it has been reported that mothers who take the HDAC inhibitor valproic acid during the first trimester of pregnancy have a significantly increased risk of their fetuses developing craniofacial abnormalities Wyszynski et al, 2005). Even though HDAC1 seems to be no essential for cranial NC differentiation, studies in zebrafish demonstrated the requirement of this protein for the proper repression of the transcription factor FoxD3 necessary for the mitfadependent melanophore development (Ignatius et al, 2008).…”

Section: Acetylationmentioning

confidence: 99%

Epigenetic landscape and miRNA involvement during neural crest development

Strobl-Mazzulla¹,

Marini²,

Buzzi³

2012

Developmental Dynamics

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The neural crest (NC) is a multipotent, migratory cell population that arises from the dorsal neural fold of vertebrate embryos. NC cells migrate extensively and differentiate into a variety of tissues, including melanocytes, bone, and cartilage of the craniofacial skeleton, peripheral and enteric neurons, glia, and smooth muscle and endocrine cells. For several years, the gene regulatory network that orchestrates NC cells development has been extensively studied. However, we have recently begun to understand that epigenetic and posttranscriptional regulation, such as miRNAs, plays important roles in NC development. In this review, we focused on some of the most recent findings on chromatin-dependent mechanisms and miRNAs regulation during vertebrate NC cells development.

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Section: Acetylationmentioning

confidence: 99%

Epigenetic landscape and miRNA involvement during neural crest development

Strobl-Mazzulla¹,

Marini²,

Buzzi³

2012

Developmental Dynamics

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“…Although there have been studies from as early as the 1960s suggesting links between major congenital malformations (MCMs) and the use of AEDs during pregnancy [6][7][8][9], the advent of the large prospective, albeit observational, epilepsy and pregnancy registries have recently added much information on the relative risks associated with the individual AEDs [5,[10][11][12][13][14][15][16][17]. The key to a successful outcome in this respect is knowledge of the individual risks and imparting these risks through preconceptual counseling, enabling women to make informed choices and allowing any alteration in therapy to be made prior to pregnancy.…”

Section: Preconceptual Counselingmentioning

confidence: 99%

“…A common theme emerging from the preliminary data from epilepsy and pregnancy registers is that sodium valproate appears to carry an elevated risk of MCM and perhaps neurodevelopmental delay compared with other AEDs [10,12,13,[15][16][17].…”

Section: Preconceptual Counselingmentioning

confidence: 99%

“…A total of 16 (10.7%; 95% CI: 6.3-16.9%) MCMs were recorded, of which three had lumbosacral spina bifida [12]. In a smaller number of cases, the Australian registry has also suggested an increased risk in mothers taking sodium valproate and reported a dose-effect relationship in that doses in excess of 1100 mg/day were associated with an enhanced rate of malformations [13].…”

Section: Preconceptual Counselingmentioning

confidence: 99%

“…As the older AEDs, which may be more teratogenic [10,12,13,29], are replaced with newer agents, which may be safer to the fetus [10,14,[30][31][32], it is possible if not probable that increased difficulty will be encountered in maintaining seizure freedom and/or control throughout pregnancy [67,68,[70][71][72][73]75].…”

Section: Joint Epilepsy-obstetric Clinicsmentioning

confidence: 99%

See 2 more Smart Citations

Managing epilepsy in pregnancy

Mawhinney

Morrow

2011

Expert Review of Obstetrics & Gynecology

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Aquaporin-4 Antibodies in Neuromyelitis Optica and Longitudinally Extensive Transverse Myelitis

Waters¹,

Jarius²,

Littleton³

et al. 2008

Arch Neurol

270

263

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Background: There is increasing recognition of antibodymediated immunotherapy-responsive neurologic diseases and a need for appropriate immunoassays. Objectives: To develop a clinically applicable quantitative assay to detect the presence of aquaporin-4 (AQP4) antibodies in patients with neuromyelitis optica and to characterize the anti-AQP4 antibodies. Design: We compared a simple new quantitative fluorescence immunoprecipitation assay (FIPA) with both indirect immunofluorescence and an AQP4-transfected cell-based assay, both previously described. We used the cell-based assay to characterize the antibodies for their immunoglobulin class, IgG subclass, and ability to induce complement C3b deposition in vitro. Setting: United Kingdom and Germany. Participants: Serum samples from patients with neuromyelitis optica (n=25) or longitudinally extensive transverse myelitis (n=11) and from relevant controls (n=78) were studied. Main Outcome Measures: Comparison of different assays for AQP4 antibodies and characterization of anti-AQP4 antibodies in patients with neuromyelitis optica. Results: We found antibodies to AQP4 in 19 of 25 patients with neuromyelitis optica (76%) using FIPA, in 20 of 25 patients with neuromyelitis optica (80%) using the cell-based assay, and in 6 of 11 patients with longitudinally extensive transverse myelitis (55%) with both assays; these assays were more sensitive than indirect immunofluorescence and 100% specific. The antibodies bound to extracellular epitope(s) of AQP4, were predominantly IgG1, and strongly induced C3b deposition. Conclusions: Aquaporin-4 is a major antigen in neuromyelitis optica, and antibodies can be detected in more than 75% of patients. Further studies on larger samples will show whether this novel FIPA is suitable for clinical use. The IgG1 antibodies bind to AQP4 on the cell surface and can initiate complement deposition. These approaches will be useful for investigation of other antibody-mediated diseases.

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Increased rate of major malformations in offspring exposed to valproate during pregnancy

Abstract: Maternal exposure to valproic acid during the first trimester of pregnancy significantly increased the risk of major malformations.

Cited by 369 publications

References 42 publications

Epigenetic landscape and miRNA involvement during neural crest development

Epigenetic landscape and miRNA involvement during neural crest development

Managing epilepsy in pregnancy

Aquaporin-4 Antibodies in Neuromyelitis Optica and Longitudinally Extensive Transverse Myelitis

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