Normal pregnancy is characterized by systemic activation of the complement system

Background. The complement system, a major component of innate immunity, has recently been implicated in the mechanisms of fetal loss and placental inflammation in the anti-phospholipid antibody syndrome. Inhibition of complement has been proposed as an absolute requirement for normal pregnancy. Yet, pregnancy is characterized by a generalized activation of the innate immune system. This study was conducted to determine whether or not normal pregnancy is associated with complement activation in the maternal circulation. Methods. Anaphylatoxins (C3a, C4a and C5a) were determined in the plasma of normal pregnant ( 20 - 42 wks; n = 134) and non-pregnant women ( n = 40). These complement split products ( C3a, C4a and C5a) were measured using specific immunoassays. Non-parametric statistics were used for analysis. Results. 1) The median plasma concentrations of C3a, C4a and C5a were significantly higher in normal pregnant women than in non-pregnant women ( all p<0.001); 2) the concentration of C3a, C4a and C5a did not change with gestational age ( p>0.05); and 3) the median plasma concentration of C3a had a positive correlation with the plasma C4a and C5a concentrations ( r = 0.36, p<0.001 and r = 0.35, p<0.001, respectively). Conclusion. 1) Normal human pregnancy is associated with evidence of complement activation, as determined by higher concentrations of the anaphylatoxins C3a, C4a and C5a in the maternal circulation; and 2) we propose that physiologic activation of the complement system during pregnancy is a compensatory mechanism aimed at protecting the host against infection.