title: Developmental neurotoxicity and anticonvulsant drugs: a possible link.
abstract: In utero exposure to antiepileptic drugs (AEDs) may affect neurodevelopment causing postnatal cognitive and behavioral alterations. Phenytoin and phenobarbital may lead to motor and learning dysfunctions in the pre-exposed children. These disorders may reflect the interference of these AEDs with the development of hippocampal and cerebellar neurons, as suggested by animal studies. Exposure to valproic acid may result in inhibition of neural stem cell proliferation and/or immature neuron migration in the cerebral cortex with consequent increased risk of neurodevelopmental impairment, such as autistic spectrum disorders. A central issue in the prevention of AED-mediated developmental effects is the identification of drugs that should be avoided in women of child-bearing potential and during pregnancy. The aim of this review is to explore the possible link between AEDs and neurodevelopmental dysfunctions both in human and in animal studies. The possible mechanisms underlying this association are also discussed.
authors.affiliation: Department of Pediatrics, University of Perugia, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Verrotti
authors.affiliation: Department of Medicine and Aging Sciences, University "G. d'Annunzio" of Chieti-Pescara, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Scaparrotta
authors.affiliation: Department of Pediatrics, University of Perugia, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Cofini
authors.affiliation: Department of Medicine and Aging Sciences, University "G. d'Annunzio" of Chieti-Pescara, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Chiarelli
authors.affiliation: Department of Medicine and Aging Sciences, University "G. d'Annunzio" of Chieti-Pescara, Italy. Electronic address: tiboni@unich.it.
authors.forename: G M
authors.initials: GM
authors.lastname: Tiboni
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects*; D001942:Breast Feeding; D002220:Carbamazepine / Q000009:adverse effects; D003072:Cognition Disorders / Q000139:chemically induced*; D002658:Developmental Disabilities / Q000139:chemically induced*; D005260:Female; D006801:Humans; D000077213:Lamotrigine; D010634:Phenobarbital / Q000009:adverse effects; D010672:Phenytoin / Q000009:adverse effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced*; D014227:Triazines / Q000009:adverse effects; D014635:Valproic Acid / Q000009:adverse effects
chemical_list: D000927:Anticonvulsants; D014227:Triazines; D002220:Carbamazepine; D014635:Valproic Acid; D010672:Phenytoin; D000077213:Lamotrigine; D010634:Phenobarbital
keywords: Anticonvulsant drug; Childbearing; Children; Developmental neurotoxicity; Pregnancy