Complement system activation in pre-eclampsia and its association with fetal growth restriction

Abstract

Fetal growth restriction (FGR) represents one of the main manifestations of placental insufficiency and is associated with adverse perinatal outcomes. In recent years, increasing attention has been paid to the role of the complement system as a key mediator of thromboinflammation in placenta-associated complications. Complement system activation is recognized as an important mechanism contributing to placental damage in pre-eclampsia (PE). Objective. To investigate complement system activation in pregnant women with PE and to determine its association with FGR. Patients and methods. This study included 40 pregnant women with severe PE. Among them, 23 had FGR, while 17 had no signs of fetal growth impairment. The control group consisted of 28 healthy patients with uncomplicated pregnancies. Circulating levels of C1q, C3a, and the C5b-9 membrane attack complex (MAC) were determined in plasma samples by an enzyme-linked immunosorbent assay. Statistical analysis was performed using the Kruskal–Wallis test and the Mann–Whitney U test. Results. Significant differences between the groups were observed for all complement biomarkers (Kruskal–Wallis test, p < 0.001). Compared with the control group, both PE subgroups (with and without FGR) demonstrated elevated levels of C1q, C3a, and MAC. Notably, patients with FGR showed significantly higher levels of C3a (p = 0.04) and MAC (p = 0.02) compared with those without FGR, indicating more pronounced complement system activation in pregnancies complicated by FGR. The most marked differences were observed for MAC, which suggests a predominant role of the terminal complement pathway in the development of placental damage. Conclusion. Complement system activation, particularly the terminal pathway, is associated with the development of FGR in PE and may be considered an important pathogenetic mechanism underlying placental insufficiency. Key words: fetal growth restriction, FGR, pre-eclampsia, complement system, C1q, C3a, membrane attack complex, MAC