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

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.

Figure 1. Identification of Cases and Controls

From the original steroid trial, 583 children were discharged alive. Of these, 4 died between discharge and follow-up and 23 were not available because they were born at a center that discontinued participation in the MFMU Network in 2001; cases and controls were selected from the remaining 556 children who were available for follow-up.