Complement and Malaria in Pregnancy
More than half of the world’s pregnancies are at risk of malaria infection each year. Malaria infection during pregnancy increases the risk of adverse birth outcomes including stillbirth, preterm birth, and fetal growth restriction. Inflammation at the maternal-fetal interface and dysregulated angiogenesis are thought to underlie malaria-associated adverse birth outcomes. Uniquely, the complement system, through its impact on both inflammatory and angiogenic pathways, has been implicated in the pathobiology of malaria-induced adverse birth outcomes. Tight regulation of the complement system is critical for healthy pregnancies and its dysregulation has been linked to poor outcomes in non-infectious pathological pregnancy syndromes. Further, blockade of excessive complement activation can reverse or prevent malaria-induced pregnancy complications including placental vascular insufficiency, low birth weight, and neurodevelopmental deficits. Together, these data indicate a critical role for complement in the pathophysiology of malaria in pregnancy and suggest that it is a target for drugs to reduce malaria-mediated adverse pregnancy outcomes.