Document Detail


Teratogenic effects of antiepileptic drugs: implications for the management of epilepsy in women of childbearing age.
MedLine Citation:
PMID:  8174516     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Exposure to antiepileptic drug (AED) treatment in utero occurs in 1 of every 250 newborns. The absolute risk of major malformations in these infants is about 7-10%, approximately 3-5% higher than in the general population. Specific risk factors include high maternal daily dosage or serum concentrations of AED, low folate levels, polytherapy, and generalized seizures during pregnancy. Adverse pregnancy outcomes, including congenital heart malformations, facial clefts, spina bifida aperta, hypospadias, growth retardation, and psychomotor and mental retardation, are associated with, although not necessarily caused by, AED exposure. Specific cognitive defects, hypertelorism, and nail hypoplasia can be causally related to specific AED exposures. To prevent teratogenic side effects, the prospective mother should be treated with AEDs only when absolutely necessary. Monotherapy with the AED that is most effective in the lowest possible daily dose (divided into at least two or three administrations) should be prescribed. High-dose folate supplementation (4-5 mg/day) reduces the risk of a neural tube defect in a child whose sibling had such a defect, but its impact on the specific teratogenic risks of AEDs is unknown. A substantial proportion of fetal malformations may be secondarily prevented by prenatal diagnosis, consisting of a fetal structural ultrasound examination at weeks 18 and 20 of gestation and, with VPA or CBZ administration, an alpha 1-fetoprotein analysis of amniotic fluid at week 16. Determination of a specific defect prevention strategy depends largely on parental attitudes toward prenatal diagnosis and termination of pregnancy, which should be discussed before conception.(ABSTRACT TRUNCATED AT 250 WORDS)
Authors:
D Lindhout; J G Omtzigt
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Epilepsia     Volume:  35 Suppl 4     ISSN:  0013-9580     ISO Abbreviation:  Epilepsia     Publication Date:  1994  
Date Detail:
Created Date:  1994-06-03     Completed Date:  1994-06-03     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  2983306R     Medline TA:  Epilepsia     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  S19-28     Citation Subset:  IM    
Affiliation:
MGC-Department of Clinical Genetics, Erasmus University Rotterdam, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Abnormalities, Drug-Induced / diagnosis,  etiology*,  prevention & control
Adult
Age Factors
Anticonvulsants / adverse effects*,  therapeutic use
Congenital Abnormalities / genetics
Dose-Response Relationship, Drug
Drug Therapy, Combination
Epilepsy / complications,  drug therapy*
Female
Folic Acid / therapeutic use
Genetic Counseling
Humans
Infant, Newborn
Pregnancy
Pregnancy Complications / drug therapy*
Prenatal Diagnosis
Risk Factors
Chemical
Reg. No./Substance:
0/Anticonvulsants; 59-30-3/Folic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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