Association of fetal inflammation and coagulation pathway gene polymorphisms with neurodevelopmental delay at age 2 years

Erin A S Clark, Lisa Mele, Ronald J. Wapner, Catherine Y. Spong, Yoram Sorokin, Alan Peaceman, Jay D. Iams, Kenneth J. Leveno, Margaret Harper, Steve N. Caritis, Menachem Miodovnik, Brian M. Mercer, John M. Thorp, Susan M. Ramin, Marshall Carpenter, Dwight J. Rouse

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Abstract

Objective: The purpose of this study was to evaluate the association between fetal inflammation and coagulation gene single-nucleotide polymorphisms (SNPs) and neurodevelopmental delay at age 2 years. Study Design: We conducted a case-controlled secondary analysis of a randomized trial of single- vs multiple-course corticosteroids. Multiplex assay assessed 46 SNPs. Cases had mental developmental and/or psychomotor delay at age 2 years. Control subjects had normal neurodevelopment. Results: One hundred twenty-five cases and 147 control subjects were analyzed. Allele frequencies were different between cases and control subjects for interleukin (IL)1β-511 (P = .009), IL4R-148 (P = .03), IL6-174 (P = .02), and IL6-176 (P = .007). Genotype frequencies were different for IL1β-511 (P = .03) and IL6-174 (P = .04). Results for IL1β-511, IL4R-148, and IL6-176 remained significant after logistic regression analysis. IL1β-511 and IL6-176 minor alleles were associated with increased risk of neurodevelopmental delay (odds ratio, 3.1; 95% confidence interval [CI], 1.2-8.2 and 2.2; 95% CI, 1.2-3.9, respectively). IL4R-148 minor allele was protective (odds ratio, 0.6; 95% CI, 0.4-0.9). Conclusion: Fetal SNPs in IL1β, IL-4R, and IL-6 may be associated with neurodevelopmental delay at age 2 years.

Original languageEnglish (US)
JournalAmerican Journal of Obstetrics and Gynecology
Volume203
Issue number1
DOIs
Publication statusPublished - Jul 2010

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Keywords

  • gene polymorphism
  • neurodevelopmental delay
  • single-nucleotide polymorphism

ASJC Scopus subject areas

  • Obstetrics and Gynecology

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