Published online April 27, 2009
PEDIATRICS Vol. 123 No. 5 May 2009, pp. 1320-1328 (doi:10.1542/peds.2008-1222)
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ARTICLE

Differential Patterns of 27 Cord Blood Immune Biomarkers Across Gestational Age

Nana Matoba, MDa,b, Yunxian Yu, MD, PhDa,c, Karen Mestan, MDa,b, Colleen Pearson, BAd, Katherin Ortiz, BAd, Nicolas Porta, MDa,b, Poul Thorsen, MD, PhDe, Kristin Skogstrand, MScf, David M. Hougaard, MD, DScf, Barry Zuckerman, MDd and Xiaobin Wang, MD, MPH, ScDa,c

a Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
b Division of Neonatology
c the Mary Ann and J. Milburn Smith Child Health Research Program, Children's Memorial Hospital and Children's Memorial Research Center, Chicago, Illinois
d Department of Pediatrics, Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts
e Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia
f Department of Clinical Biochemistry and Immunology, Statens Serum Institut, Copenhagen, Denmark

OBJECTIVES. 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.

PATIENTS AND 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 (≤32, 33–36, and ≥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]-1{alpha}, MIP-1β, 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-1β, 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 β, and tumor necrosis factor β).

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.

Key Words: cord blood • biomarkers • prematurity

Abbreviations: BDNF—brain-derived neurotrophic factor • FDR—false-discovery rate • GM-CSF—granulocyte/macrophage colony-stimulating factor • IFN-{gamma}—interferon {gamma} • IL—interleukin • MCP-1—monocyte chemoattractant protein 1 • MIF—macrophage migration inhibitory factor • MIP—macrophage inflammatory protein • MMP-9—matrix metalloproteinase 9 • NT—neurotrophin • RANTES—regulated on activation, normal T-cell expressed and secreted • sIL-6r{alpha}—soluble IL-6 receptor {alpha} • sTNF RI—soluble tumor necrosis factor receptor I • TGF-β—transforming growth factor β • TNF-{alpha}—tumor necrosis factor {alpha} • TNF-β—tumor necrosis factor β • TREM-1—triggering receptor expressed on myeloid cells 1 • OR—odds ratio • CI—confidence interval

Accepted Aug 22, 2008.


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