title: Antiepileptic medication during pregnancy: does fetal genotype affect outcome?
abstract: 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.
authors.affiliation: Division of Human Development, The Medical School, University of Manchester, Manchester, M13 OJH, United Kingdom. diane.e.atkinson@manchester.ac.uk
authors.forename: Diane E
authors.initials: DE
authors.lastname: Atkinson
authors.forename: Sophie
authors.initials: S
authors.lastname: Brice-Bennett
authors.forename: Stephen W
authors.initials: SW
authors.lastname: D'Souza
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000014:Abnormalities, Drug-Induced / Q000235:genetics*; D000927:Anticonvulsants / Q000009:adverse effects* / Q000378:metabolism; D004827:Epilepsy / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D005313:Fetal Death / Q000139:chemically induced* / Q000235:genetics; D005333:Fetus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D018507:Gene Expression Regulation, Developmental; D020022:Genetic Predisposition to Disease; D005838:Genotype; D048788:Growth and Development / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008431:Maternal-Fetal Exchange; D010641:Phenotype; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D021041:Placental Circulation; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D011297:Prenatal Exposure Delayed Effects; D018570:Risk Assessment
chemical_list: D018528:ATP-Binding Cassette Transporters; D000927:Anticonvulsants