ArticleEpilepsia open2019
Fetal hypoxia and hyperglycemia in the formation of phenytoin-induced cleft lip and maxillary hypoplasia.
Article in Epilepsia open, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
3 citing papers in PubMed, 8 citations in OpenAlex.
- Molecular Regulation of Palatogenesis and Clefting: An Integrative Analysis of Genetic, Epigenetic Networks, and Environmental Interactions.International journal of molecular sciences · 2025Review
- Phenytoin Inhibits Cell Proliferation through microRNA-196a-5p in Mouse Lip Mesenchymal Cells.International journal of molecular sciences · 2021Article
- Fetal hypoxia and hyperglycemia in the formation of phenytoin-induced cleft lip and maxillary hypoplasia.Epilepsia open · 2019Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivePhenytoin exposure during the first trimester of pregnancy increases the risk of maxillary hypoplasia and cleft lip. The etiology of phenytoin embryopathy is unknown. Interestingly, phenytoin is also known to induce hyperglycemia in humans as well as rats. This study uses a rat model of fetal phenytoin syndrome to examine the role of hyperoxia, hyperglycemia, and arachidonic acid deficiency in the development of cleft lip and maxillary hypoplasia.
methodsPregnant rats were dosed with phenytoin during the critical period of lip development (day 11 of pregnancy) with or without supplemental oxygen, insulin, or arachidonic acid. The fetuses from all studies were examined at term.
resultsThe frequency of cleft lip and maxillary hypoplasia was reduced by treating dams at the time of phenytoin exposure with either increased oxygen or insulin. However, in fetuses from phenytoin-treated dams dosed with arachidonic acid, the incidence of severe lip deformities remained the same although there was an increase in normal and mildly affected fetuses. Interestingly, this occurred in embryos from hyperglycemic dams. SIGNIFICANCE: Together, the results from these experiments suggest phenytoin-induced malformations may be a multifactorial process as malformations were not solely linked to a hyperglycemic state of the dam.
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