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


METHODS
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).


CONCLUSIONS
Fetal SNPs in IL1beta, IL-4R, and IL-6 may be associated with neurodevelopmental delay at age 2 years.
Clark
Erin A S
EA
Department of Obstetrics and Gynecology, School of Medicine, University of Utah, Salt Lake City, UT 84132, USA. erin.clark@hsc.utah.edu
Mele
Lisa
L
Wapner
Ronald J
RJ
Spong
Catherine Y
CY
Sorokin
Yoram
Y
Peaceman
Alan
A
Iams
Jay D
JD
Leveno
Kenneth J
KJ
Harper
Margaret
M
Caritis
Steve N
SN
Miodovnik
Menachem
M
Mercer
Brian M
BM
Thorp
John M
JM
Ramin
Susan M
SM
Carpenter
Marshall
M
Rouse
Dwight J
DJ
D001778:Blood Coagulation Disorders / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D002675:Child, Preschool; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000235:genetics*; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics; D016015:Logistic Models; D008297:Male; D009422:Nervous System Diseases / Q000097:blood / Q000235:genetics*; D010920:Placenta / Q000473:pathology; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy
D007378:Interleukins; D004247:DNA