Anaphylatoxins in preterm and term labor

Abstract

Objective: The complement system plays a central role in the first line of defense against invading pathogens, and its activation involves the release of potent proinflammatory mediators such as anaphylatoxins C3a, C4a and C5a. The aim of this study was to determine whether differences existed in maternal plasma anaphylatoxin concentrations between patients with term and preterm parturition. Study design: A cross-sectional study was designed to determine the plasma anaphylatoxin concentrations in 296 pregnant women in the following groups: 1) normal pregnancy between 20-36 6/7 weeks (ns64); 2) term not in labor (ns70); 3) term in labor (ns60); and 4) preterm labor with intact membranes (ns102). Women with preterm labor were classified into: a) term delivery (ns24); b) preterm delivery without intra-amniotic infection (IAI) (ns62); and c) preterm delivery with IAI (ns16). Concentrations of C3a, C4a and C5a were determined by ELISAs. Statistical analysis was conducted with nonparametric methods. Results: 1) The median plasma C5a concentration was lower in women at term in labor than in those not in labor (P-0.001). In contrast, there were no differences in plasma C3a and C4a concentrations between the two groups (P)0.05). 2) Among patients with preterm labor, those with IAI had a higher median plasma C5a concentration than those without IAI and those who delivered at term (post-hoc tests P-0.001 and Ps0.01, respectively). When comparing the preterm labor subgroups with normal pregnancy, only women with preterm delivery and IAI had a median plasma C5a concentration higher than that of normal pregnant women (Kruskal-Wallis P-0.001, post hoc test P-0.001). There was no difference in the plasma C4a concentration among patients with preterm labor. The median plasma C3a concentration in patients with preterm labor with IAI was higher than in those without IAI (Kruskal-Wallis Ps0.01, and post-hoc test Ps0.005). There was no difference in the plasma C3a concentrations between women with preterm labor who delivered at term and those with preterm delivery, with or without IAI. In addition, no differences were observed in the median plasma C3a concentration between women with normal pregnancy and those in each of the preterm labor subgroups. Conclusions:The maternal plasma concentration of anaphylatoxin C5a is increased in women with preterm labor and IAI, but not in spontaneous labor at term.

Early Elevations of the Complement Activation Fragment C3a and Adverse Pregnancy Outcomes

“…29 Given the important connection between the complement system and inflammation, it is remarkable that complement activation as it relates to preterm birth has only received the attention of a few authors. 13,30–34 It is of great interest that we found significantly higher levels of C3a in early pregnancy in women who subsequently had an early rupture of the fetal membranes at any gestation in later pregnancy compared with women who had no premature rupture of the membranes. When we examined mean levels of C3a in women with premature rupture of the membranes across these categories of gestational age, we found a dose–response with the highest concentrations of C3a among women who had premature rupture of the membranes between 20 and 34 weeks of gestation and the lowest levels among women with a term premature rupture of the membranes (Table 4).…”

Choriodecidual leukocytes display a unique gene expression signature in spontaneous labor at term

“…Such a pathway has been implicated in susceptibility to viral infections [69] and the pathological process of preterm labor [70][71][72][73][74], but not in the physiological process of labor at term. Therefore, this finding requires further investigation.…”

Maternal coding variants in complement receptor 1 and spontaneous idiopathic preterm birth

“…There is a growing body of literature describing activation of the complement system and adverse pregnancy outcomes, including PTB (Vaisbuch et al 2010; Soto et al 2005). There have been a number of reports illustrating that an increased level of fragment Bb (FBb) early in pregnancy is associated with an increased risk of PTB < 34 weeks (Lynch et al 2008).…”