Association of polymorphisms in neuroprotection and oxidative stress genes and neurodevelopmental outcomes after preterm birth.

MedStar author(s):
Citation: Obstetrics & Gynecology. 120(3):542-50, 2012 Sep.PMID: 22914463Institution: MedStar Health Research InstituteForm of publication: Journal ArticleMedline article type(s): Journal Article | Research Support, N.I.H., ExtramuralSubject headings: *Cerebral Palsy/ge [Genetics] | *Infant, Premature, Diseases/ge [Genetics] | *Intellectual Disability/ge [Genetics] | *Polymorphism, Single Nucleotide | *Psychomotor Disorders/ge [Genetics] | *Receptors, N-Methyl-D-Aspartate/ge [Genetics] | *Vasoactive Intestinal Peptide/ge [Genetics] | Case-Control Studies | Child, Preschool | Developmental Disabilities/ge [Genetics] | Female | Genetic Markers | Homeostasis/ge [Genetics] | Humans | Infant | Infant, Newborn | Infant, Premature | Infant, Premature, Diseases/mo [Mortality] | Logistic Models | Male | Oxidative Stress/ge [Genetics] | Psychological Tests | Receptors, Immunologic/ge [Genetics]Local holdings: Available online from MWHC library: 1995 - present, Available in print through MWHC library: 1999 - 2006ISSN:
  • 0029-7844
Name of journal: Obstetrics and gynecologyAbstract: CONCLUSION: Vasoactive intestinal polypeptipe and GRIN3A SNPs may be associated with cerebral palsy at age 2 in children born preterm.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.OBJECTIVE: To estimate the associations between polymorphisms in neuronal homeostasis, neuroprotection, and oxidative stress candidate genes and neurodevelopmental disability.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).All authors: Caritis SN, Carpenter M, Clark EA, Costantine MM, Lai Y, Malone FD, Mercer BM, Miodovnik M, O'Sullivan MJ, Peaceman AM, Ramin SM, Rouse DJ, Sorokin Y, Spong CY, Thorp JM JrDate added to catalog: 2013-09-17
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Item type Current library Collection Call number Status Date due Barcode
Journal Article MedStar Authors Catalog Article Available 22914463

Available online from MWHC library: 1995 - present, Available in print through MWHC library: 1999 - 2006

CONCLUSION: Vasoactive intestinal polypeptipe and GRIN3A SNPs may be associated with cerebral palsy at age 2 in children born preterm.

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.

OBJECTIVE: To estimate the associations between polymorphisms in neuronal homeostasis, neuroprotection, and oxidative stress candidate genes and neurodevelopmental disability.

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).

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