Adverse effects of prenatal and early postnatal exposure to antiepileptic drugs

Validation from clinical and basic researches

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
JournalBrain and Development
DOIs
Publication statusAccepted/In press - 2016 Dec 31

Fingerprint

Anticonvulsants
Valproic Acid
Research
Brain
Neocortex
Carbamazepine
Phenobarbital
Autistic Disorder
Intellectual Disability
Epilepsy
Fetus
Stem Cells
Neurons

Keywords

  • Antiepileptic drugs
  • Breastfeeding
  • Congenital malformation
  • Epigenetics
  • Neurodevelopmental disorders

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Developmental Neuroscience
  • Clinical Neurology

Cite this

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title = "Adverse effects of prenatal and early postnatal exposure to antiepileptic drugs: Validation from clinical and basic researches",
abstract = "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.",
keywords = "Antiepileptic drugs, Breastfeeding, Congenital malformation, Epigenetics, Neurodevelopmental disorders",
author = "Kimino Fujimura and Takayuki Mitsuhashi and Takao Takahashi",
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AU - Mitsuhashi, Takayuki

AU - Takahashi, Takao

PY - 2016/12/31

Y1 - 2016/12/31

N2 - 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.

AB - 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.

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