title: Inflammatory and Angiogenic Factors at Mid-Pregnancy Are Associated with Spontaneous Preterm Birth in a Cohort of Tanzanian Women.
abstract: OBJECTIVE
  Preterm birth (PTB) is the leading cause of perinatal mortality worldwide, with the greatest burden occurring in resource-constrained settings. Based on the hypothesis that altered placental angiogenesis and inflammation early in pregnancy lead to PTB, we examined whether levels of inflammatory and angiogenic mediators, measured early in pregnancy, were predictive of spontaneous PTB (sPTB).
  
  
  METHODS
  Plasma samples were collected from a prospective cohort of primigravid Tanzanian women between 12-27 weeks gestation. A panel of 18 markers was screened on a training cohort of 426 women. Markers associated with sPTB in the training cohort were repeated in a test cohort of 628 women. All markers were measured by ELISA.
  
  
  RESULTS
  In both the training and test cohorts plasma levels of IL-18BP, sICAM-1, sEndoglin and CHI3L1 were elevated and Leptin was lower at enrollment in women who subsequently experienced sPTB. In multivariate analysis women with plasma levels of CHI3L1, C5a, sICAM-1, AngptL3, sEndgolin, sFlt-1 and IL-18BP in the highest quartile had an increased risk of sPTB compared with those in the lowest quartile. Women with Leptin and Ang2 in the highest quartile had a reduced risk of sPTB compared with women in the lowest quartile.
  
  
  CONCLUSIONS
  Levels of angiogenic and inflammatory mediators measured at mid-pregnancy were associated with subsequent sPTB. These findings provide insight into mechanisms underlying sPTB and suggest biomarkers that may have clinical utility in risk-stratifying pregnancies.
authors.affiliation: SAR Laboratories, Sandra Rotman Centre for Global Health, University Health Network-Toronto General Hospital, University of Toronto, Toronto, Canada; Institute of Medical Science, University of Toronto, Toronto, Canada.
authors.forename: Chloe R
authors.initials: CR
authors.lastname: McDonald
authors.affiliation: Department of Global Health and Population, Harvard School of Public Health, Boston, Massachusetts, United States of America; Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Darling
authors.affiliation: SAR Laboratories, Sandra Rotman Centre for Global Health, University Health Network-Toronto General Hospital, University of Toronto, Toronto, Canada.
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Conroy
authors.affiliation: SAR Laboratories, Sandra Rotman Centre for Global Health, University Health Network-Toronto General Hospital, University of Toronto, Toronto, Canada.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Tran
authors.affiliation: SAR Laboratories, Sandra Rotman Centre for Global Health, University Health Network-Toronto General Hospital, University of Toronto, Toronto, Canada.
authors.forename: Ana
authors.initials: A
authors.lastname: Cabrera
authors.affiliation: Department of Medicine, University of Washington, Seattle, Washington, United States of America.
authors.forename: W Conrad
authors.initials: WC
authors.lastname: Liles
authors.affiliation: Department of Global Health and Population, Harvard School of Public Health, Boston, Massachusetts, United States of America; Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Molin
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.
authors.forename: Said
authors.initials: S
authors.lastname: Aboud
authors.affiliation: Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.
authors.forename: Willy
authors.initials: W
authors.lastname: Urassa
authors.affiliation: Department of Global Health and Population, Harvard School of Public Health, Boston, Massachusetts, United States of America; Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, United States of America; Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Wafaie W
authors.initials: WW
authors.lastname: Fawzi
authors.affiliation: SAR Laboratories, Sandra Rotman Centre for Global Health, University Health Network-Toronto General Hospital, University of Toronto, Toronto, Canada; Institute of Medical Science, University of Toronto, Toronto, Canada; Tropical Disease Unit, Division of Infectious Diseases, Department of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Kain
mesh_terms: D054392:Adipokines / Q000097:blood; D015703:Antigens, CD / Q000097:blood; D015415:Biomarkers / Q000097:blood; D044383:Black People; D000071451:Chitinase-3-Like Protein 1; D015331:Cohort Studies; D000071063:Endoglin; D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D037102:Lectins / Q000097:blood; D020738:Leptin / Q000097:blood; D011247:Pregnancy; D047928:Premature Birth / Q000209:etiology*; D011446:Prospective Studies; D011956:Receptors, Cell Surface / Q000097:blood; D012306:Risk; D013636:Tanzania; D055815:Young Adult
chemical_list: D054392:Adipokines; D015703:Antigens, CD; D015415:Biomarkers; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; C064206:ENG protein, human; D000071063:Endoglin; D036341:Intercellular Signaling Peptides and Proteins; D037102:Lectins; D020738:Leptin; D011956:Receptors, Cell Surface; C118370:interleukin-18 binding protein; D018799:Intercellular Adhesion Molecule-1