Unexplained intrauterine fetal death is accompanied by activation of complement

Abstract

Activation of the complement system has recently been implicated in the mechanisms of fetal loss in the antiphospholipid syndrome. It is, however, possible that complement activation is also involved in other causes of fetal death in the second and third trimesters of pregnancy. We therefore conducted a study to determine whether fetal death is associated with changes in the maternal plasma concentrations of complement split products or anaphylatoxins (C3a, C4a and C5a). A cross-sectional study was designed to include normal pregnant women (n=60) and patients with fetal death (n=60). Patients with fetal death were classified according to the cause of fetal demise into: a) unexplained (n=44); b) associated with preeclampsia (n=8); and c) associated with chromosomal abnormalities or major congenital fetal anomalies (n=8). The plasma concentrations of C3a, C4a and C5a were measured using sensitive and specific ELISAs. Non-parametric statistics were used for analysis. A P value of <0.05 was considered significant. 1) The median plasma concentration of C5a was higher in patients with fetal death than in normal pregnant women [median 16 ng/mL (range 4.5-402.5) vs. median 11.6 ng/mL (range 1.2-87.1), respectively; P<0.001]; 2) patients with an unexplained fetal death and those associated with preeclampsia had a higher median plasma C5a concentration than normal pregnant women (P=0.002 and P<0.001, respectively); 3) no differences were observed in the maternal plasma concentrations of C3a and C4a among the study groups. Unexplained fetal death is associated with evidence of complement activation.