Document Detail


Association of polymorphisms in neuroprotection and oxidative stress genes and neurodevelopmental outcomes after preterm birth.
MedLine Citation:
PMID:  22914463     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To estimate the associations between polymorphisms in neuronal homeostasis, neuroprotection, and oxidative stress candidate genes and neurodevelopmental disability.
METHODS: This was a nested case-control analysis of a randomized trial of magnesium sulfate administered to women at imminent risk for early (before 32 weeks) preterm birth for the prevention of death or cerebral palsy in their offspring. We evaluated 21 single-nucleotide polymorphisms (SNPs) in 17 genes associated with neuronal homeostasis, neuroprotection, or oxidative stress in umbilical cord blood. Cases included infant deaths (n=43) and children with cerebral palsy (n=24), mental delay (Bayley Mental Developmental Index less than 70; n=109), or psychomotor delay (Bayley Psychomotor Developmental Index less than 70; n=91) diagnosed. Controls were race-matched and sex-matched children with normal neurodevelopment. Associations between each SNP and each outcome were assessed in logistic regression models assuming an additive genetic pattern, conditional on maternal race and infant sex, and adjusting for study drug assignment, gestational age at birth, and maternal education.
RESULTS: The odds of cerebral palsy were increased more than 2.5 times for each copy of the minor allele of vasoactive intestinal polypeptipe (VIP, rs17083008) (adjusted odds ratio 2.67, 95% confidence interval 1.09-6.55, P=.03) and 4.5 times for each copy of the minor allele of N-methyl-D-aspartate receptor subunit 3A (GRIN3A, rs3739722) (adjusted odds ratio 4.67, 95% CI 1.36-16.01, P=.01). The association between the advanced glycosylation end product-specific receptor (AGER, rs3134945) SNP and mental delay was modulated by study drug allocation (P=.02).
CONCLUSION: Vasoactive intestinal polypeptipe and GRIN3A SNPs may be associated with cerebral palsy at age 2 in children born preterm.
Authors:
Maged M Costantine; Erin A S Clark; Yinglei Lai; Dwight J Rouse; Catherine Y Spong; Brian M Mercer; Yoram Sorokin; John M Thorp; Susan M Ramin; Fergal D Malone; Marshall Carpenter; Menachem Miodovnik; Mary J O'Sullivan; Alan M Peaceman; Steve N Caritis
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Obstetrics and gynecology     Volume:  120     ISSN:  1873-233X     ISO Abbreviation:  Obstet Gynecol     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-08-23     Completed Date:  2012-10-29     Revised Date:  2014-08-12    
Medline Journal Info:
Nlm Unique ID:  0401101     Medline TA:  Obstet Gynecol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  542-50     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Case-Control Studies
Cerebral Palsy / genetics*
Child, Preschool
Developmental Disabilities / genetics
Female
Genetic Markers
Homeostasis / genetics
Humans
Infant
Infant, Newborn
Infant, Premature
Infant, Premature, Diseases / genetics*,  mortality
Intellectual Disability / genetics*
Logistic Models
Male
Oxidative Stress / genetics
Polymorphism, Single Nucleotide*
Psychological Tests
Psychomotor Disorders / genetics*
Receptors, Immunologic / genetics
Receptors, N-Methyl-D-Aspartate / genetics*
Vasoactive Intestinal Peptide / genetics*
Grant Support
ID/Acronym/Agency:
HD19897/HD/NICHD NIH HHS; HD21410/HD/NICHD NIH HHS; HD21414/HD/NICHD NIH HHS; HD27860/HD/NICHD NIH HHS; HD27861/HD/NICHD NIH HHS; HD27869/HD/NICHD NIH HHS; HD27905/HD/NICHD NIH HHS; HD27915/HD/NICHD NIH HHS; HD27917/HD/NICHD NIH HHS; HD34116/HD/NICHD NIH HHS; HD34122/HD/NICHD NIH HHS; HD34136/HD/NICHD NIH HHS; HD34208/HD/NICHD NIH HHS; HD34210/HD/NICHD NIH HHS; HD36801/HD/NICHD NIH HHS; HD40485/HD/NICHD NIH HHS; HD40500/HD/NICHD NIH HHS; HD40512/HD/NICHD NIH HHS; HD40544/HD/NICHD NIH HHS; HD40545/HD/NICHD NIH HHS; HD40560/HD/NICHD NIH HHS; HD53907/HD/NICHD NIH HHS; M01-RR-000080/RR/NCRR NIH HHS; U10 HD027869/HD/NICHD NIH HHS; U10 HD053097/HD/NICHD NIH HHS; UL1 RR024989/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/GRIN3A protein, human; 0/Genetic Markers; 0/Receptors, Immunologic; 0/Receptors, N-Methyl-D-Aspartate; 0/advanced glycosylation end-product receptor; 37221-79-7/Vasoactive Intestinal Peptide
Comments/Corrections

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