title: The interrelationship of complement-activation fragments and angiogenesis-related factors in early pregnancy and their association with pre-eclampsia.
abstract: OBJECTIVE
  To determine the interrelationships during early pregnancy of complement-activation fragments Bb, C3a and sC5b-9, and angiogenesis-related factors placental growth factor (PiGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng), and their associations with pre-eclampsia.
  
  
  METHODS
  Prospective cohort study.
  
  
  METHODS
  Denver complement study (June 2005-June 2008).
  
  
  METHODS
  A total of 668 pregnant women with singleton gestations, recruited between 10 and 15 weeks of gestation.
  
  
  METHODS
  Using univariable and multivariable logistic regression analysis, concentrations of complement-activation fragments and angiogenesis-related factors were compared between 10 and 15 weeks of gestation in women who subsequently did or did not develop pre-eclampsia. Interrelationships between these variables were tested using the non-parametric Spearman rank correlation coefficient.
  
  
  METHODS
  Pre-eclampsia. The association of complement-activation fragments and angiogenesis-related factors with obesity was also examined.
  
  
  RESULTS
  The mean (+/-SD) levels of complement Bb in early pregnancy among women who did and did not develop pre-eclampsia were 0.84 (+/-0.26) microg/ml and 0.69 (+/-0.2) microg/ml, respectively (P = 0.001). Concentrations of PiGF were significantly (P = 0.01) lower (31 +/- 12 pg/ml) in early pregnancy in the pre-eclamptic group of women, as compared with the normotensive group (39 +/- 32 pg/ml). The adjusted odds ratio (AOR) of Bb and PiGF were 2.1 (CI = 1.4-3.1, P < 0.0003) and 0.2 (CI = 0.07-0.7, P = 0.01), respectively. There was no significant difference in the levels of C3a, sC5b-9, sFlt-1 and sEng in early pregnancy among women who developed pre-eclampsia, compared with women who remained normotensive during pregnancy. Higher levels of Bb (P = 0.0001) and C3a (P = 0.03), and lower levels of sFlt-1 (P = 0.0002) and sEng (P = 0.0001) were found among women with obesity, compared with non-obese controls. No meaningful relationships were found between the complement-activation fragments and the angiogenesis-related factors.
  
  
  CONCLUSIONS
  In this cohort during early pregnancy, increased concentrations of complement-activation factor Bb and lower concentrations of PiGF were associated with the development of pre-eclampsia later in pregnancy.
authors.affiliation: Department of Obstetrics and Gynecology, University of Colorado Denver School of Medicine, 12631 East 17th Avenue, Aurora, CO 80045, USA. anne.lynch@ucdenver.edu
authors.forename: A M
authors.initials: AM
authors.lastname: Lynch
authors.forename: J R
authors.initials: JR
authors.lastname: Murphy
authors.forename: R S
authors.initials: RS
authors.lastname: Gibbs
authors.forename: R J
authors.initials: RJ
authors.lastname: Levine
authors.forename: P C
authors.initials: PC
authors.lastname: Giclas
authors.forename: J E
authors.initials: JE
authors.lastname: Salmon
authors.forename: V M
authors.initials: VM
authors.lastname: Holers
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D003166:Complement Activating Enzymes / Q000378:metabolism*; D000071063:Endoglin; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D009765:Obesity / Q000150:complications* / Q000378:metabolism; D011225:Pre-Eclampsia / Q000175:diagnosis / Q000209:etiology*; D011247:Pregnancy; D011446:Prospective Studies; D011956:Receptors, Cell Surface / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; C064206:ENG protein, human; D000071063:Endoglin; D008565:Membrane Proteins; C098069:PIGF protein, human; D011956:Receptors, Cell Surface; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1; D003166:Complement Activating Enzymes