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

Am J Obstet Gynecol. 2010 Jul;203(1):83.e1-83.e10. doi: 10.1016/j.ajog.2010.01.047. Epub 2010 Apr 24.

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Blood Coagulation Disorders / blood
  • Blood Coagulation Disorders / genetics*
  • Case-Control Studies
  • Child, Preschool
  • DNA / chemistry
  • DNA / genetics
  • Female
  • Genetic Variation
  • Genotype
  • Humans
  • Inflammation / blood
  • Inflammation / genetics*
  • Interleukins / biosynthesis
  • Interleukins / genetics
  • Logistic Models
  • Male
  • Nervous System Diseases / blood
  • Nervous System Diseases / genetics*
  • Placenta / pathology
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide
  • Pregnancy

Substances

  • Interleukins
  • DNA

Grants and funding