Differential patterns of 27 cord blood immune biomarkers across gestational age.
OBJECTIVE
Inflammation has been associated with preterm delivery and adverse neonatal outcomes such as cerebral palsy and chronic lung disease. However, no study to date has simultaneously examined a wide range of inflammatory mediators and their relationship to gestational age. We sought to describe the distribution of immune biomarkers in cord blood across gestational age and to investigate the association between biomarker level patterns and preterm birth.


METHODS
As part of a large-scale molecular epidemiological study of preterm birth conducted at Boston Medical Center, this study analyzed both clinical and biomarker data from 927 births. Twenty-seven biomarkers were simultaneously quantified by immunoassay. The associations between the quartiles of 27 biomarkers and 3 gestational groups (< or =32, 33-36, and > or =37 weeks) were analyzed. Biomarkers found to be significant were further analyzed for dose-response correlation with preterm birth by logistic regression, adjusted for pertinent demographic and clinical factors.


RESULTS
The 27 biomarkers could be classified into 1 of 3 groups: (1) biomarkers increased in preterm birth (interleukin [IL]-2, IL-4, IL-5, IL-8, IL-10, monocyte chemoattractant protein 1, macrophage inflammatory protein [MIP]-1alpha, MIP-1beta, soluble IL-6 receptor alpha, tumor necrosis factor alpha, soluble tumor necrosis factor receptor I, and TREM-1 [triggering receptor expressed on myeloid cells 1]); (2) biomarkers decreased in preterm birth (brain-derived neurotrophic factor, IL-1beta, IL-18, matrix metalloproteinase 9, and neurotrophin 3); and (3) biomarkers not associated with preterm birth (IL-6, IL-12, IL-17, granulocyte/macrophage colony-stimulating factor, interferon gamma, macrophage migration inhibitory factor, neurotrophin 4, RANTES [regulated on activation, normal T-cell expressed and secreted], transforming growth factor beta, and tumor necrosis factor beta).


CONCLUSIONS
Biomarkers have different directions of association with prematurity; for significant biomarkers, the strength of association increases with biomarker concentration. Our results provide important information that could be used to guide additional studies aimed at determining mechanisms that contribute to preterm birth.
Matoba
Nana
N
Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA. n-matoba@northwestern.edu
Yu
Yunxian
Y
Mestan
Karen
K
Pearson
Colleen
C
Ortiz
Katherin
K
Porta
Nicolas
N
Thorsen
Poul
P
Skogstrand
Kristin
K
Hougaard
David M
DM
Zuckerman
Barry
B
Wang
Xiaobin
X
D000328:Adult; D015415:Biomarkers / Q000097:blood*; D018932:Chemokine CCL2 / Q000097:blood; D054405:Chemokine CCL3 / Q000097:blood; D054407:Chemokine CCL4 / Q000097:blood; D018946:Chemokine CCL5 / Q000097:blood; D000068800:Etanercept; D005260:Female; D005312:Fetal Blood / Q000737:chemistry / Q000276:immunology*; D005865:Gestational Age; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007231:Infant, Newborn; D007378:Interleukins / Q000097:blood; D016015:Logistic Models; D008263:Macrophage Migration-Inhibitory Factors / Q000097:blood; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008562:Membrane Glycoproteins / Q000097:blood; D009414:Nerve Growth Factors / Q000097:blood; D011247:Pregnancy; D047928:Premature Birth / Q000276:immunology*; D011971:Receptors, Immunologic / Q000097:blood; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D016212:Transforming Growth Factor beta / Q000097:blood; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D055815:Young Adult
D015415:Biomarkers; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D007074:Immunoglobulin G; D007378:Interleukins; D008263:Macrophage Migration-Inhibitory Factors; D008562:Membrane Glycoproteins; D009414:Nerve Growth Factors; D011971:Receptors, Immunologic; D018124:Receptors, Tumor Necrosis Factor; C408842:TREM1 protein, human; D016212:Transforming Growth Factor beta; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D020780:Matrix Metalloproteinase 9; D000068800:Etanercept