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

Maged 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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)542-550
Number of pages9
JournalObstetrics and Gynecology
Volume120
Issue number3
DOIs
StatePublished - Sep 2012

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Premature Birth
Cerebral Palsy
Single Nucleotide Polymorphism
Oxidative Stress
Genes
Homeostasis
Logistic Models
Alleles
Odds Ratio
Mothers
Magnesium Sulfate
N-Methyl-D-Aspartate Receptors
Fetal Blood
Pharmaceutical Preparations
Gestational Age
Parturition
Confidence Intervals
Education
Neuroprotection

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

Costantine, M., Clark, E. A. S., Lai, Y., Rouse, D. J., Spong, C. Y., Mercer, B. M., ... Caritis, S. N. (2012). Association of polymorphisms in neuroprotection and oxidative stress genes and neurodevelopmental outcomes after preterm birth. Obstetrics and Gynecology, 120(3), 542-550. https://doi.org/10.1097/AOG.0b013e318265f232

Association of polymorphisms in neuroprotection and oxidative stress genes and neurodevelopmental outcomes after preterm birth. / Costantine, Maged; Clark, Erin A S; Lai, Yinglei; Rouse, Dwight J.; Spong, Catherine Y.; Mercer, Brian M.; Sorokin, Yoram; Thorp, John M.; Ramin, Susan M.; Malone, Fergal D.; Carpenter, Marshall; Miodovnik, Menachem; O'Sullivan, Mary J.; Peaceman, Alan M.; Caritis, Steve N.

In: Obstetrics and Gynecology, Vol. 120, No. 3, 09.2012, p. 542-550.

Research output: Contribution to journalArticle

Costantine, M, Clark, EAS, Lai, Y, Rouse, DJ, Spong, CY, Mercer, BM, Sorokin, Y, Thorp, JM, Ramin, SM, Malone, FD, Carpenter, M, Miodovnik, M, O'Sullivan, MJ, Peaceman, AM & Caritis, SN 2012, 'Association of polymorphisms in neuroprotection and oxidative stress genes and neurodevelopmental outcomes after preterm birth', Obstetrics and Gynecology, vol. 120, no. 3, pp. 542-550. https://doi.org/10.1097/AOG.0b013e318265f232
Costantine, Maged ; Clark, Erin A S ; Lai, Yinglei ; Rouse, Dwight J. ; Spong, Catherine Y. ; Mercer, Brian M. ; Sorokin, Yoram ; Thorp, John M. ; Ramin, Susan M. ; Malone, Fergal D. ; Carpenter, Marshall ; Miodovnik, Menachem ; O'Sullivan, Mary J. ; Peaceman, Alan M. ; Caritis, Steve N. / Association of polymorphisms in neuroprotection and oxidative stress genes and neurodevelopmental outcomes after preterm birth. In: Obstetrics and Gynecology. 2012 ; Vol. 120, No. 3. pp. 542-550.
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abstract = "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.",
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AU - Costantine, Maged

AU - Clark, Erin A S

AU - Lai, Yinglei

AU - Rouse, Dwight J.

AU - Spong, Catherine Y.

AU - Mercer, Brian M.

AU - Sorokin, Yoram

AU - Thorp, John M.

AU - Ramin, Susan M.

AU - Malone, Fergal D.

AU - Carpenter, Marshall

AU - Miodovnik, Menachem

AU - O'Sullivan, Mary J.

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