Document Detail

Antiepileptic drugs and the fetal epigenome.
MedLine Citation:
PMID:  23016625     Owner:  NLM     Status:  Publisher    
Antiepileptic drugs (AEDs) can lower maternal folate and increase maternal homocysteine levels, which are known to affect the methyl cycle and hence DNA methylation levels. The influence of in utero exposure to AEDs on fetal DNA methylation was investigated. Genome-wide fetal epigenomic profiles were determined using the Infinium 27K BeadArray from Illumina (San Diego, CA, U.S.A.). The Infinium array measures approximately 27,000 CpG loci associated with 14,496 genes at single-nucleotide resolution. Eighteen cord blood samples (nine samples from babies exposed to AEDs and nine controls) from otherwise uncomplicated pregnancies were compared. Unsupervised hierarchic clustering was used to compare the calculated methylation profiles. A clear distinction between the methylation profiles of samples from babies exposed to AEDs in utero compared with controls was detected. These data provide evidence of an epigenetic effect associated with antenatal AED and high-dose folate supplementation during pregnancy. The differences in fetal DNA methylation of those exposed to AEDs shows that a genome-wide effect of methylation is evident. In addition, the epigenetic changes observed appear to be, in this limited sample, independent of extremes of birth weight centiles. These preliminary data highlight possible mechanisms by which AEDs might influence fetal outcomes and the potential of optimizing AED-specific folate supplementation regimens to offset these effects.
Richard D Emes; Harry Clifford; Kim E Haworth; William E Farrell; Anthony A Fryer; William D Carroll; Khaled M K Ismail
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-9-27
Journal Detail:
Title:  Epilepsia     Volume:  -     ISSN:  1528-1167     ISO Abbreviation:  Epilepsia     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-9-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2983306R     Medline TA:  Epilepsia     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 International League Against Epilepsy.
School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, Leicestershire, United Kingdom Institute of Science and Technology in Medicine, Keele University School of Medicine, Stoke-on-Trent, Staffordshire, United Kingdom Department of Paediatrics, Derbyshire Children's Hospital, Derby, United Kingdom School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
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