Association of Fetal Inflammation and Coagulation Pathway Gene Polymorphisms with Neurodevelopmental Delay at Age 2 Years

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Citation

Clark, Erin A. S.; Mele, Lisa; Wapner, Ronald J.; Spong, Catherine Y.; Sorokin, Yoram; Peaceman, Alan M.; Iams, Jay D.; Leveno, Kenneth J.; Harper, Margaret A.; & Caritis, Steve N., et al. (2010). Association of Fetal Inflammation and Coagulation Pathway Gene Polymorphisms with Neurodevelopmental Delay at Age 2 Years. American Journal of Obstetrics & Gynecology, 203(1), 83.e1-10. PMCID: PMC2900538

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)1beta-511 (P = .009), IL4R-148 (P = .03), IL6-174 (P = .02), and IL6-176 (P = .007). Genotype frequencies were different for IL1beta-511 (P = .03) and IL6-174 (P = .04). Results for IL1beta-511, IL4R-148, and IL6-176 remained significant after logistic regression analysis. IL1beta-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 IL1beta, IL-4R, and IL-6 may be associated with neurodevelopmental delay at age 2 years.

URL

http://dx.doi.org/10.1016/j.ajog.2010.01.047

Reference Type

Journal Article

Year Published

2010

Journal Title

American Journal of Obstetrics & Gynecology

Author(s)

Clark, Erin A. S.
Mele, Lisa
Wapner, Ronald J.
Spong, Catherine Y.
Sorokin, Yoram
Peaceman, Alan M.
Iams, Jay D.
Leveno, Kenneth J.
Harper, Margaret A.
Caritis, Steve N.
Miodovnik, Menachem
Mercer, Brian M.
Thorp, John M., Jr.
Ramin, Susan M.
Carpenter, Marshall W.
Rouse, Dwight J., for the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network

PMCID

PMC2900538

ORCiD

Thorp - 0000-0002-9307-6690