15: Bioinformatics analysis of biomarkers reveal differential maternal-fetal contributions to spontaneous preterm birth pathophysiology


      To document racial disparity between African Americans (AA) and Caucasians (C) in pathophysiologic pathways and underlying disease functions associated with spontaneous preterm birth (PTB) induced by distinct maternal and fetal biomarker response.

      Study Design

      36 candidate biomarkers from PTB pathways were analyzed in maternal and fetal plasma from 191 subjects [105 PTB (<36 weeks): 59 AA and 46 C; 86 term births: 40 AA and 46 C (37-41 weeks)]. The contribution of dysregulated maternal and fetal biomarkers between PTB and term birth to distinct pathways were mapped using Ingenuity Pathway Analysis (IPA). Biomarkers that met the significance p-value cutoff of 0.2 (FDR correction) were matched within the IPA web application to determine attributing biological functions that were most enriched for each compartment and race. Fishers exact tests calculated the significance of the associations between biomarkers and biological functions (5.95E-04 to 2.78E-02).


      In a combined analysis of races, IPA identified both fetal (Eotaxin,ICAM-1,IGF-I,IL-1β,MIP1α,MCP-3,TGFβ1,TNFα, TNFR-I,TNFR-II,VEGF) and maternal (Eotaxin,ICAM-1,IGF-I,IL-1β,IL-2,IL-6R,ANGPT2,FAS ligand,FGF Basic,IL-5,IL-10,IL-13) biomarkers of cellular movement and cell-to-cell interaction associated with PTB. Data stratified by race demonstrated fetal biomarkers (Eotaxin,FGF Basic,ICAM-1,IGF-I,IL-1β,IL8,IL-10 MIP1-α,TGF-β1,TNFα,TNFR-I,TNFR-II,VEGF) contribute to PTB in C (p= 4.53E-03). Fetal contribution was not evident in AA PTB. Maternal biomarkers (IL-1β,IL-6R,IL8,MIP1α,TIMP-1,TNF-α,TNFR-I, ANGPT2,FGF Basic) associated with AA PTB (p = 5.95E-04), and (IL-RA,IL8, TNFR-1,VGEF) associated with C PTB (p=2.78E-02).


      Maternal-fetal biomarker differences result in distinct pathophysiologic pathways leading to PTB in different races. Markers of fetal inflammation and hematologic dysfunctions in C and maternal inflammatory markers in AA contribute to PTB. PTB biomarkers and pathways are not universal and may change based on individuals own risk factors including race.
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