| Antiepileptic medication during pregnancy: does fetal genotype affect outcome? | |
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MedLine Citation:
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PMID: 17597651 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Congenital abnormalities and impaired development in childhood are attributable to fetal exposure to antiepileptic drugs (AEDs). Pregnancy registries set up to obtain information about the potential risks of fetal exposure to AEDs, in particular major congenital malformations (MCMs), suggest that valproate exposure increases the frequency of congenital malformations more than other AEDs. Furthermore, follow-up studies have drawn attention to cognitive impairments in later childhood after prenatal exposure to valproate. Fetal exposure to AEDs may be influenced by drug transporting proteins in the placenta, including P-glycoprotein (P-gp), multidrug resistance protein (MRP) 1, and breast cancer resistance protein (BCRP). Their location in the syncytiotrophoblast plasma membrane, at the interface of the maternal and fetal circulations, allows these transport proteins to efflux xenobiotics back to the mother and offers the fetus protection from medications taken during pregnancy. Genetic variations in the expression and activity of these transport proteins may influence fetal exposure to AEDs and thus the risk of teratogenicity. Identification of a hierarchy of haplotypes ranging from susceptible to protective of congenital abnormalities could assist genetic counseling, in assessing fetal risks from exposure to AEDs. |
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Authors:
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Diane E Atkinson; Sophie Brice-Bennett; Stephen W D'Souza |
Publication Detail:
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Type: Journal Article; Review |
Journal Detail:
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Title: Pediatric research Volume: 62 ISSN: 0031-3998 ISO Abbreviation: Pediatr. Res. Publication Date: 2007 Aug |
Date Detail:
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Created Date: 2007-08-16 Completed Date: 2007-09-19 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0100714 Medline TA: Pediatr Res Country: United States |
Other Details:
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Languages: eng Pagination: 120-7 Citation Subset: IM |
Affiliation:
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Division of Human Development, The Medical School, University of Manchester, Manchester, M13 OJH, United Kingdom. diane.e.atkinson@manchester.ac.uk |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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ATP-Binding Cassette Transporters
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genetics,
metabolism Abnormalities, Drug-Induced / genetics* Anticonvulsants / adverse effects*, metabolism Epilepsy / drug therapy*, genetics, metabolism, physiopathology Female Fetal Death / chemically induced*, genetics Fetus / drug effects*, metabolism, physiopathology Gene Expression Regulation, Developmental Genetic Predisposition to Disease Genotype Growth and Development / drug effects, genetics Humans Maternal-Fetal Exchange Phenotype Placenta / drug effects*, metabolism, physiopathology Placental Circulation Polymorphism, Genetic Pregnancy Pregnancy Complications / drug therapy*, genetics, metabolism, physiopathology Prenatal Exposure Delayed Effects* Risk Assessment |
| Chemical | |
Reg. No./Substance:
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0/ATP-Binding Cassette Transporters; 0/Anticonvulsants |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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