title: Complement Activation in Placental Malaria.
abstract: Sixty percent of all pregnancies worldwide occur in malaria endemic regions. Pregnant women are at greater risk of malaria infection than their non-pregnant counterparts and have a higher risk of adverse birth outcomes including low birth weight resulting from intrauterine growth restriction and/or preterm birth. The complement system plays an essential role in placental and fetal development as well as the host innate immune response to malaria infection. Excessive or dysregulated complement activation has been associated with the pathobiology of severe malaria and with poor pregnancy outcomes, dependent and independent of infection. Here we review the role of complement in malaria and pregnancy and discuss its part in mediating altered placental angiogenesis, malaria-induced adverse birth outcomes, and disruptions to the in utero environment with possible consequences on fetal neurodevelopment. A detailed understanding of the mechanisms underlying adverse birth outcomes, and the impact of maternal malaria infection on fetal neurodevelopment, may lead to biomarkers to identify at-risk pregnancies and novel therapeutic interventions to prevent these complications.
authors.affiliation: Sandra Rotman Laboratories, Sandra Rotman Centre for Global Health, Toronto General Research Institute, University Health Network, TorontoON, Canada; Department of Global Health and Population, Harvard School of Public Health, BostonMA, USA.
authors.forename: Chloe R
authors.initials: CR
authors.lastname: McDonald
authors.affiliation: Sandra Rotman Laboratories, Sandra Rotman Centre for Global Health, Toronto General Research Institute, University Health Network, Toronto ON, Canada.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Tran
authors.affiliation: Sandra Rotman Laboratories, Sandra Rotman Centre for Global Health, Toronto General Research Institute, University Health Network, TorontoON, Canada; Tropical Disease Unit, Division of Infectious Diseases, Department of Medicine, University of Toronto, TorontoON, Canada.
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Kain
keywords: angiogenesis; complement; inflammation; malaria; neurodevelopment; placental malaria; pregnancy