Background
Malaria 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 Findings
In 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 1820 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.
Conclusions
The data suggest that maternalfetal 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.