Abstract
BackgroundMalaria and hypertension are major causes of maternal mortality in tropical countries, especially during first pregnancies, but evidence for a relationship between these syndromes is contradictory.Methods and FindingsIn a cross-sectional survey of Tanzanian parturients, the rate of hypertension was similar in placental malaria (PM)-positive (11/85 = 13%) and PM-negative (73/602 = 12%) individuals. However, we found that PM was associated with hypertension in first-time mothers aged 18–20 y but not other mothers. Hypertension was also associated with histologic features of chronic malaria, which is common in first-time mothers. Levels of soluble vascular endothelial growth factor receptor 1 (sVEGFR1), a preeclampsia biomarker, were elevated in first-time mothers with either PM, hypertension, or both, but levels were not elevated in other mothers with these conditions. In first-time mothers with PM, the inflammatory mediator vascular endothelial growth factor (VEGF) was localized to maternal macrophages in the placenta, while sVEGFR1, its soluble inhibitor, was localized to the fetal trophoblast.ConclusionsThe data suggest that maternal–fetal conflict involving the VEGF pathway occurs during PM, and that sVEGFR1 may be involved in the relationship between chronic PM and hypertension in first-time mothers. Because placental inflammation causes poor fetal outcomes, we hypothesize that fetal mechanisms that promote sVEGFR1 expression may be under selective pressure during first pregnancies in malaria-endemic areas.
Highlights
Placental malaria (PM) caused by Plasmodium falciparum preferentially affects first-time mothers: rates of up to 70% occur in regions of sub-Saharan Africa, where low birth weight due to placental malaria (PM) is estimated to cause 200,000 infant deaths each year
The data suggest that maternal–fetal conflict involving the vascular endothelial growth factor (VEGF) pathway occurs during PM, and that soluble vascular endothelial growth factor receptor 1 (sVEGFR1) may be involved in the relationship between chronic PM and hypertension in first-time mothers
Because placental inflammation causes poor fetal outcomes, we hypothesize that fetal mechanisms that promote sVEGFR1 expression may be under selective pressure during first pregnancies in malaria-endemic areas
Summary
Placental malaria (PM) caused by Plasmodium falciparum preferentially affects first-time mothers: rates of up to 70% occur in regions of sub-Saharan Africa, where low birth weight due to PM is estimated to cause 200,000 infant deaths each year. One of the most serious consequences of infection is that this parasite can multiply in the placenta of a pregnant woman This ‘‘placental malaria’’ is very harmful to the mother and to the fetus; it leads to low birth weight and is estimated to be responsible for the deaths every year of about 200,000 babies within their first year of life. A woman who is pregnant for the first time is most likely to suffer from placental malaria, and to have her placenta become highly infected and extremely inflamed. If she later becomes pregnant again, she will be protected to some extent by antibodies she has developed against the parasite
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