The interrelationship of complement-activation fragments and angiogenesis-related factors in early pregnancy and their association with pre-eclampsia

BJOG. 2010 Mar;117(4):456-62. doi: 10.1111/j.1471-0528.2009.02473.x. Epub 2010 Jan 14.


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.

Design: Prospective cohort study.

Setting: Denver complement study (June 2005-June 2008).

Population: 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.

Main outcome measure: 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.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD / metabolism*
  • Biomarkers / metabolism
  • Complement Activating Enzymes / metabolism*
  • Endoglin
  • Female
  • Humans
  • Membrane Proteins / metabolism*
  • Obesity / complications*
  • Obesity / metabolism
  • Pre-Eclampsia / diagnosis
  • Pre-Eclampsia / etiology*
  • Pregnancy
  • Prospective Studies
  • Receptors, Cell Surface / metabolism*
  • Vascular Endothelial Growth Factor Receptor-1 / metabolism*


  • Antigens, CD
  • Biomarkers
  • ENG protein, human
  • Endoglin
  • Membrane Proteins
  • PIGF protein, human
  • Receptors, Cell Surface
  • FLT1 protein, human
  • Vascular Endothelial Growth Factor Receptor-1
  • Complement Activating Enzymes