Complement activation in primiparous women from a malaria endemic area is associated with reduced birthweight.

The hallmark of placental malaria (PM) due to Plasmodium falciparum infection is the accumulation of mature-stage parasites, monocytes and macrophages in the maternal vascular bed of the placenta. The mechanisms leading to morbidity and mortality in PM are incompletely understood. However, an inflammatory response in the placenta has been related to both severe anemia in the mother and low birthweight (<2500 g) in the newborn. In this study we analyzed whether complement activation as a mediator of inflammation could contribute to poor pregnancy outcome in PM. The concentrations of the soluble terminal complement complex (TCC) were measured as an indicator of complement activation in placental, cord and peripheral blood samples from 146 women from a malaria endemic area. Placental and cord plasma samples of primiparous women, a group vulnerable to PM, showed significantly higher levels of TCC than multiparous women. Additionally, in women with malaria history during pregnancy or placental infection by P. falciparum at delivery, the TCC levels in the corresponding placental and cord plasma samples were significantly higher than in the malaria negative group. In multiple regression analysis parity was shown to be the main determinant of TCC levels. Placental plasma samples corresponding to babies weighing less than 2700 g had significantly higher levels of TCC than babies carrying more weight. In conclusion, both primiparity and P. falciparum infection were related to a local increase of complement activation in the placentas. Association between reduced birthweight and higher levels of TCC in placental blood suggests a role for complement activation in influencing the pregnancy outcome in malaria exposed women.