Dysregulated biomarkers induce distinct pathways in preterm birth

L. Brou, L. M. Almli, B. D. Pearce, G. Bhat, C. O. Drobek, S. Fortunato, Ramkumar Menon

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Objective: To document racial disparity in biomarker concentrations in maternal/fetal plasma and amniotic fluid between African Americans and European Americans with spontaneous preterm birth (PTB; cases) and normal term birth (controls), and their contribution to distinct pathophysiological pathways of PTB. Design Nested case-control study. Setting The Perinatal Research Center, Nashville, Tennessee, USA. Sample Maternal and fetal plasma and amniotic fluid samples were collected from 105 cases (59 African American and 46 European American) and 86 controls (40 African American and 46 European American). Methods Thirty-six biomarkers were analysed using the protein microarray approach. Main outcome measures Differences in biomarker concentrations between cases and controls of different races in maternal, fetal and intra-amniotic compartments, and the risk of PTB. Dysregulated biomarker-induced PTB pathways associated with PTB in each race were determined using ingenuity pathway analysis (IPA). Results Racial disparity was observed in biomarker concentrations in each compartment between cases and controls: amniotic fluid, IL8 and MIP1α differed between case and controls in European Americans, whereas ANGPT2, Eotaxin, ICAM-1, IL-1β, IL1RA, RANTES and TNFα differed between case and controls in African Americans. In both races the FAS ligand, MCP-3 and TNFR-I differed between cases and controls. For fetal plasma, ANGPT2, Eotaxin, FGF basic, ICAM-1, IGF-I, IL10, IL-1β, IL2, IP10 KGF, MCP-3, MIP1α, PDGF-BB, TGFα, TGFβ1, TIMP1, TNFα, TNFR-I, TNFR-II and VEGF differed between cases and controls in European Americans, whereas only MMP7 differed between cases and controls in African Americans. IL-8 differed between cases and controls in both races. For maternal plasma, IL1RA, MMP7 and VEGF differed between cases and controls in European Americans, whereas ANGPT2, FGF basic, IL-1β, IL5, IL6R, KGF, MCP-3, MIP1α, TIMP1 and TNFα differed between cases and controls in African Americans. ANG, IL8 and TNFR-I differed between cases and controls in both races. Conclusions We conclude that: (1) biomarker concentrations in maternal, fetal and intra-amniotic compartments differ between cases and controls; (2) there is racial disparity in the biomarker profile in each of the compartments; (3) substantial numbers of dysregulated fetal plasma biomarkers contribute to PTB in European Americans, whereas maternal plasma biomarkers contribute to PTB in African Americans; and (4) both inflammation and haematological functions are associated with PTB in European Americans, but maternal proinflammatory changes dominate PTB in African Americans. Biomarker analyses document racial disparity and the distinct pathophysiological contributions from different compartments that can determine pregnancy outcome.

Original languageEnglish (US)
Pages (from-to)458-473
Number of pages16
JournalBJOG: An International Journal of Obstetrics and Gynaecology
Volume119
Issue number4
DOIs
StatePublished - Mar 2012

Fingerprint

Premature Birth
Biomarkers
African Americans
Mothers
Receptors, Tumor Necrosis Factor, Type I
Amniotic Fluid
Interleukin-8
Interleukin-1
Intercellular Adhesion Molecule-1
Vascular Endothelial Growth Factor A
Chemokine CCL11
Term Birth
Chemokine CCL5
Protein Array Analysis
Interleukin-5
Pregnancy Outcome
Contraception
Insulin-Like Growth Factor I
Interleukin-10
Interleukin-2

Keywords

  • Bioinformatics
  • cytokines
  • ethnic disparity
  • infection
  • inflammation
  • ingenuity pathway analysis
  • prematurity

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

Dysregulated biomarkers induce distinct pathways in preterm birth. / Brou, L.; Almli, L. M.; Pearce, B. D.; Bhat, G.; Drobek, C. O.; Fortunato, S.; Menon, Ramkumar.

In: BJOG: An International Journal of Obstetrics and Gynaecology, Vol. 119, No. 4, 03.2012, p. 458-473.

Research output: Contribution to journalArticle

Brou, L. ; Almli, L. M. ; Pearce, B. D. ; Bhat, G. ; Drobek, C. O. ; Fortunato, S. ; Menon, Ramkumar. / Dysregulated biomarkers induce distinct pathways in preterm birth. In: BJOG: An International Journal of Obstetrics and Gynaecology. 2012 ; Vol. 119, No. 4. pp. 458-473.
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T1 - Dysregulated biomarkers induce distinct pathways in preterm birth

AU - Brou, L.

AU - Almli, L. M.

AU - Pearce, B. D.

AU - Bhat, G.

AU - Drobek, C. O.

AU - Fortunato, S.

AU - Menon, Ramkumar

PY - 2012/3

Y1 - 2012/3

N2 - Objective: To document racial disparity in biomarker concentrations in maternal/fetal plasma and amniotic fluid between African Americans and European Americans with spontaneous preterm birth (PTB; cases) and normal term birth (controls), and their contribution to distinct pathophysiological pathways of PTB. Design Nested case-control study. Setting The Perinatal Research Center, Nashville, Tennessee, USA. Sample Maternal and fetal plasma and amniotic fluid samples were collected from 105 cases (59 African American and 46 European American) and 86 controls (40 African American and 46 European American). Methods Thirty-six biomarkers were analysed using the protein microarray approach. Main outcome measures Differences in biomarker concentrations between cases and controls of different races in maternal, fetal and intra-amniotic compartments, and the risk of PTB. Dysregulated biomarker-induced PTB pathways associated with PTB in each race were determined using ingenuity pathway analysis (IPA). Results Racial disparity was observed in biomarker concentrations in each compartment between cases and controls: amniotic fluid, IL8 and MIP1α differed between case and controls in European Americans, whereas ANGPT2, Eotaxin, ICAM-1, IL-1β, IL1RA, RANTES and TNFα differed between case and controls in African Americans. In both races the FAS ligand, MCP-3 and TNFR-I differed between cases and controls. For fetal plasma, ANGPT2, Eotaxin, FGF basic, ICAM-1, IGF-I, IL10, IL-1β, IL2, IP10 KGF, MCP-3, MIP1α, PDGF-BB, TGFα, TGFβ1, TIMP1, TNFα, TNFR-I, TNFR-II and VEGF differed between cases and controls in European Americans, whereas only MMP7 differed between cases and controls in African Americans. IL-8 differed between cases and controls in both races. For maternal plasma, IL1RA, MMP7 and VEGF differed between cases and controls in European Americans, whereas ANGPT2, FGF basic, IL-1β, IL5, IL6R, KGF, MCP-3, MIP1α, TIMP1 and TNFα differed between cases and controls in African Americans. ANG, IL8 and TNFR-I differed between cases and controls in both races. Conclusions We conclude that: (1) biomarker concentrations in maternal, fetal and intra-amniotic compartments differ between cases and controls; (2) there is racial disparity in the biomarker profile in each of the compartments; (3) substantial numbers of dysregulated fetal plasma biomarkers contribute to PTB in European Americans, whereas maternal plasma biomarkers contribute to PTB in African Americans; and (4) both inflammation and haematological functions are associated with PTB in European Americans, but maternal proinflammatory changes dominate PTB in African Americans. Biomarker analyses document racial disparity and the distinct pathophysiological contributions from different compartments that can determine pregnancy outcome.

AB - Objective: To document racial disparity in biomarker concentrations in maternal/fetal plasma and amniotic fluid between African Americans and European Americans with spontaneous preterm birth (PTB; cases) and normal term birth (controls), and their contribution to distinct pathophysiological pathways of PTB. Design Nested case-control study. Setting The Perinatal Research Center, Nashville, Tennessee, USA. Sample Maternal and fetal plasma and amniotic fluid samples were collected from 105 cases (59 African American and 46 European American) and 86 controls (40 African American and 46 European American). Methods Thirty-six biomarkers were analysed using the protein microarray approach. Main outcome measures Differences in biomarker concentrations between cases and controls of different races in maternal, fetal and intra-amniotic compartments, and the risk of PTB. Dysregulated biomarker-induced PTB pathways associated with PTB in each race were determined using ingenuity pathway analysis (IPA). Results Racial disparity was observed in biomarker concentrations in each compartment between cases and controls: amniotic fluid, IL8 and MIP1α differed between case and controls in European Americans, whereas ANGPT2, Eotaxin, ICAM-1, IL-1β, IL1RA, RANTES and TNFα differed between case and controls in African Americans. In both races the FAS ligand, MCP-3 and TNFR-I differed between cases and controls. For fetal plasma, ANGPT2, Eotaxin, FGF basic, ICAM-1, IGF-I, IL10, IL-1β, IL2, IP10 KGF, MCP-3, MIP1α, PDGF-BB, TGFα, TGFβ1, TIMP1, TNFα, TNFR-I, TNFR-II and VEGF differed between cases and controls in European Americans, whereas only MMP7 differed between cases and controls in African Americans. IL-8 differed between cases and controls in both races. For maternal plasma, IL1RA, MMP7 and VEGF differed between cases and controls in European Americans, whereas ANGPT2, FGF basic, IL-1β, IL5, IL6R, KGF, MCP-3, MIP1α, TIMP1 and TNFα differed between cases and controls in African Americans. ANG, IL8 and TNFR-I differed between cases and controls in both races. Conclusions We conclude that: (1) biomarker concentrations in maternal, fetal and intra-amniotic compartments differ between cases and controls; (2) there is racial disparity in the biomarker profile in each of the compartments; (3) substantial numbers of dysregulated fetal plasma biomarkers contribute to PTB in European Americans, whereas maternal plasma biomarkers contribute to PTB in African Americans; and (4) both inflammation and haematological functions are associated with PTB in European Americans, but maternal proinflammatory changes dominate PTB in African Americans. Biomarker analyses document racial disparity and the distinct pathophysiological contributions from different compartments that can determine pregnancy outcome.

KW - Bioinformatics

KW - cytokines

KW - ethnic disparity

KW - infection

KW - inflammation

KW - ingenuity pathway analysis

KW - prematurity

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