Abstract
Placental infections with Plasmodium falciparum are associated with fetal growth restriction resulting in low birth weight (LBW). The mechanisms that mediate these effects have yet to be completely described; however, they are likely to involve inflammatory processes and dysregulation of angiogenesis. Soluble endoglin (sEng), a soluble receptor of transforming growth factor (TGF)-β previously associated with preeclampsia in pregnant women and with severe malaria in children, regulates the immune system and influences angiogenesis. We hypothesized that sEng may play a role in development of LBW associated with placental malaria (PM). Plasma levels of sEng were measured in women (i) followed prospectively throughout pregnancy in Cameroon (n = 52), and (ii) in a case-control study at delivery in Malawi (n = 479). The relationships between sEng levels and gravidity, peripheral and placental parasitemia, gestational age, and adverse outcomes of PM including maternal anemia and LBW were determined. In the longitudinal cohort from Cameroon, 28 of 52 women (54%) experienced at least one malaria infection during pregnancy. In Malawi we enrolled two aparasitemic gravidity-matched controls for every case with PM. sEng levels varied over the course of gestation and were significantly higher in early and late gestation as compared to delivery (P<0.006 and P<0.0001, respectively). Circulating sEng levels were higher in primigravidae than multigravidae from both Cameroon and Malawi, irrespective of malarial infection status (p<0.046 and p<0.001, respectively). Peripheral parasitemia in Cameroonian women and PM in Malawian women were each associated with elevated sEng levels following correction for gestational age and gravidity (p = 0.006 and p = 0.033, respectively). Increased sEng was also associated with the delivery of LBW infants in primigravid Malawian women (p = 0.017); the association was with fetal growth restriction (p = 0.003) but not pre-term delivery (p = 0.286). Increased circulating maternal sEng levels are associated with P. falciparum infection in pregnancy and with fetal growth restriction in primigravidae with PM.
Highlights
Low birth weight (LBW) is a well documented effect of malaria infections in pregnancy [1], and increases the risk of death in the first two years of life [2,3]
The purpose of this study was to determine whether Soluble endoglin (sEng) levels are increased with malaria in pregnancy and placental malaria (PM), and whether the increases are associated with delivery of LBW infants
By measuring sEng in maternal plasma at various stages of pregnancy in a longitudinal study in Cameroon and in a large case-control cross-sectional study from Malawi, we were able to show that circulating sEng levels were associated with poor outcomes of malaria infection in pregnancy. sEng was increased in pregnant women with peripheral malaria parasitemia during pregnancy, and peripheral sEng levels at delivery were increased in the presence of PM
Summary
Low birth weight (LBW) is a well documented effect of malaria infections in pregnancy [1], and increases the risk of death in the first two years of life [2,3] These effects are most highly associated with Plasmodium falciparum infections of the placenta referred to as placental malaria (PM) [4]. Since over 85 million pregnant women are at risk of P. falciparum infection every year [6], there is a need to better understand the mediators of poor clinical outcomes associated with PM Such information should lead to better diagnosis and treatment of mothers who are at risk of having LBW babies. Inflammation and angiogenesis are not mutually exclusive processes, but have complementary functions in the control of infection and injury and the limitation of detrimental tissue neo-vascularization [14,15]
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