Journal
BRAIN & DEVELOPMENT
Volume 39, Issue 8, Pages 635-643Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.braindev.2017.03.026
Keywords
Antiepileptic drugs; Congenital malformation; Neurodevelopmental disorders; Breastfeeding; Epigenetics
Categories
Funding
- Japan Society for the Promotion of Science (JSPS) [20390299, 23390276, 26293248, 25461560, 22791001]
- Mother and Child Health Foundation
- Japan Epilepsy Research Foundation
- Keio Gijuku Fukuzawa Memorial Fund
- Kawano Masanori Memorial Public Interest Incorporated Foundation
- Japan Foundation for Pediatric Research
- Grants-in-Aid for Scientific Research [20390299, 26293248, 22791001, 17H04232, 23390276, 25461560] Funding Source: KAKEN
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Epilepsy requires the long-term administration of antiepileptic drugs (AEDs), and thus, we must consider the effects of prenatal AED exposure on fetus when treating female patients of child bearing age. Large prospective clinical researches in humans have demonstrated the following: (1) prenatal exposure to valproic acid (VPA), carbamazepine, and phenobarbital increases the risk of congenital malformations in a dose-dependent manner and (2) prenatal exposure to VPA increases the risk of higher brain function impairments including intellectual disabilities and autistic spectrum disorders in the offspring. Furthermore, basic researches in animals have shown that prenatal exposure to specific AEDs causes microscopic structural abnormalities in the fetal brain. Specifically, prenatal exposure to VPA has been reported to inhibit the differentiation of neural progenitor cells during the early to middle phases of neuronogenesis, leading to increased number of projection neurons in the superficial layers of postnatal neocortices in mice. It is indispensable to prescribe AEDs that are associated with lower risk of congenital malformations and impairment of higher brain functions as well as to administer them at requisite minimum doses. (C) 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
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