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

Research output: Contribution to journalArticle

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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
StatePublished - Jul 2010

Fingerprint

Interleukin-6
Inflammation
Genes
Single Nucleotide Polymorphism
Confidence Intervals
Alleles
Odds Ratio
Interleukins
Interleukin-1
Gene Frequency
Adrenal Cortex Hormones
Logistic Models
Genotype
Regression Analysis

Keywords

  • gene polymorphism
  • neurodevelopmental delay
  • single-nucleotide polymorphism

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

Association of fetal inflammation and coagulation pathway gene polymorphisms with neurodevelopmental delay at age 2 years. / Clark, Erin A S; Mele, Lisa; Wapner, Ronald J.; Spong, Catherine Y.; Sorokin, Yoram; Peaceman, Alan; Iams, Jay D.; Leveno, Kenneth J.; Harper, Margaret; Caritis, Steve N.; Miodovnik, Menachem; Mercer, Brian M.; Thorp, John M.; Ramin, Susan M.; Carpenter, Marshall; Rouse, Dwight J.

In: American Journal of Obstetrics and Gynecology, Vol. 203, No. 1, 07.2010.

Research output: Contribution to journalArticle

Clark, EAS, Mele, L, Wapner, RJ, Spong, CY, Sorokin, Y, Peaceman, A, Iams, JD, Leveno, KJ, Harper, M, Caritis, SN, Miodovnik, M, Mercer, BM, Thorp, JM, Ramin, SM, Carpenter, M & Rouse, DJ 2010, 'Association of fetal inflammation and coagulation pathway gene polymorphisms with neurodevelopmental delay at age 2 years', American Journal of Obstetrics and Gynecology, vol. 203, no. 1. https://doi.org/10.1016/j.ajog.2010.01.047
Clark, Erin A S ; Mele, Lisa ; Wapner, Ronald J. ; Spong, Catherine Y. ; Sorokin, Yoram ; Peaceman, Alan ; Iams, Jay D. ; Leveno, Kenneth J. ; Harper, Margaret ; Caritis, Steve N. ; Miodovnik, Menachem ; Mercer, Brian M. ; Thorp, John M. ; Ramin, Susan M. ; Carpenter, Marshall ; Rouse, Dwight J. / Association of fetal inflammation and coagulation pathway gene polymorphisms with neurodevelopmental delay at age 2 years. In: American Journal of Obstetrics and Gynecology. 2010 ; Vol. 203, No. 1.
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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.",
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T1 - Association of fetal inflammation and coagulation pathway gene polymorphisms with neurodevelopmental delay at age 2 years

AU - Clark, Erin A S

AU - Mele, Lisa

AU - Wapner, Ronald J.

AU - Spong, Catherine Y.

AU - Sorokin, Yoram

AU - Peaceman, Alan

AU - Iams, Jay D.

AU - Leveno, Kenneth J.

AU - Harper, Margaret

AU - Caritis, Steve N.

AU - Miodovnik, Menachem

AU - Mercer, Brian M.

AU - Thorp, John M.

AU - Ramin, Susan M.

AU - Carpenter, Marshall

AU - Rouse, Dwight J.

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N2 - 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.

AB - 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.

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