title: Alteration of bioelectrically-controlled processes in the embryo: a teratogenic mechanism for anticonvulsants.
abstract: Maternal use of anticonvulsants during the first trimester of pregnancy has been associated with an elevated risk of major congenital malformations in the offspring. Whether the increased risk is caused by the specific pharmacological mechanisms of certain anticonvulsants, the underlying epilepsy, or common genetic or environmental risk factors shared by epilepsy and malformations has been controversial. We hypothesize that anticonvulsant therapies during pregnancy that attain more successful inhibition of neurotransmission might lead to both better seizure control in the mother and stronger alteration of bioelectrically-controlled processes in the embryo that result in structural malformations. We propose that development of pharmaceuticals that do not alter cell resting transmembrane voltage levels could result in safer drugs.
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, MA, United States. Electronic address: shernan@hsph.harvard.edu.
authors.forename: Sonia
authors.initials: S
authors.lastname: Hernández-Díaz
authors.affiliation: Department of Biology, and Center for Regenerative and Developmental Biology, Tufts University, Medford, MA, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Levin
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000453:epidemiology / Q000209:etiology*; D000927:Anticonvulsants / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D047108:Embryonic Development / Q000187:drug effects / Q000502:physiology; D004827:Epilepsy / Q000188:drug therapy; D005260:Female; D006801:Humans; D011247:Pregnancy; D009435:Synaptic Transmission / Q000187:drug effects; D013723:Teratogens / Q000494:pharmacology / Q000633:toxicity
chemical_list: D000927:Anticonvulsants; D013723:Teratogens
keywords: Anticonvulsants; Developmental biology; Neurotransmission; Structural malformations