Document Detail


Prenatal antiepileptic exposure associates with neonatal DNA methylation differences.
MedLine Citation:
PMID:  22419127     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Antiepileptic drugs (AEDs) are used to treat a variety of neuropsychiatric illnesses commonly encountered in women during their reproductive years, including epilepsy and bipolar disorder. Despite their widespread use, the impact of prenatal exposure on fetal development remains obscure. To evaluate whether AEDs taken by pregnant mothers influence DNA methylation patterns in their neonates, DNA was extracted from the umbilical cord blood of 201 neonates whose mothers were treated for neuropsychiatric illness during pregnancy and interrogated across 27,578 CpG sites using the Illumina HumanMethylation27 BeadChip. The association of each methylation value with the cumulative duration of prenatal AED exposure was examined using a linear mixed model. The average methylation level across all CpG sites was calculated for each subject, and this global methylation measure was evaluated similarly. Neonates with a longer duration of AED exposure in pregnancy showed a decrease in average global methylation (p = 0.0045). Further, DNA methylation of CpG sites in 14 genes significantly decreased with the duration of prenatal AED exposure even after adjusting for multiple comparisons (FDR < 0.05). For a small subset (n = 19) of these neonates, a second tissue, placenta, was available in addition to cord blood. Methylation of 3 of these 14 CpG sites was also significantly decreased in placental tissue. These novel data suggest decreased DNA methylation in neonates of mothers who took AEDs during pregnancy. The long-term stability and potential impact of these changes warrant further attention, and caution may be warranted before prescribing AEDs to pregnant women.
Authors:
Alicia K Smith; Karen N Conneely; D Jeffrey Newport; Varun Kilaru; James W Schroeder; Page B Pennell; Bettina T Knight; Joseph C Cubells; Zachary N Stowe; Patricia A Brennan
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-05-01
Journal Detail:
Title:  Epigenetics : official journal of the DNA Methylation Society     Volume:  7     ISSN:  1559-2308     ISO Abbreviation:  Epigenetics     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-06-13     Completed Date:  2012-10-11     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  101265293     Medline TA:  Epigenetics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  458-63     Citation Subset:  IM    
Affiliation:
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA. aksmit3@emory.edu
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MeSH Terms
Descriptor/Qualifier:
Anticonvulsants / adverse effects*,  blood,  pharmacology
Carbamazepine / adverse effects,  blood,  pharmacology
CpG Islands
DNA Methylation*
Depressive Disorder, Major / drug therapy,  pathology
Drug Evaluation
Female
Fetal Blood / drug effects*
Genome, Human / drug effects*
Gestational Age
Humans
Infant, Newborn / blood*
Male
Placenta / drug effects,  pathology
Pregnancy
Prenatal Exposure Delayed Effects / chemically induced*
Valproic Acid / adverse effects,  blood,  pharmacology
Grant Support
ID/Acronym/Agency:
K01 MH085806/MH/NIMH NIH HHS; MH085806/MH/NIMH NIH HHS; P50 MH 68,036/MH/NIMH NIH HHS; P50 MH077928/MH/NIMH NIH HHS; RC1 MH088609/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/Anticonvulsants; 298-46-4/Carbamazepine; 99-66-1/Valproic Acid
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