Differential Activation of Fetal Hofbauer Cells in Primigravidas Is Associated with Decreased Birth Weight in Symptomatic Placental Malaria

BACKGROUND: Placental malaria is a leading global cause of low birth weight neonates, especially in first-time mothers. To better understand the role of innate immunity in placental malaria, we investigated the relationships between histopathological markers of placental malaria, fetal and maternal macrophage responses, and perinatal outcomes in a cross-sectional case control study of pregnant women presenting with symptomatic malaria at the time of delivery. RESULTS: Primigravidas showed increased hemozoin deposition in placental villi (p=0.02), syncytiotrophoblasts (p=0.01), and fetal Hofbauer cells (p=0.01). The percentage of hemozoin-positive villi negatively correlated with infant birth weight (regression coefficient [b] = -0.03 kg decrease in birth weight per % increase in hemozoin-positive villi, p=0.035). Malaria-infected placentas showed a twofold increase in Hofbauer cells (p<0.001) and maternal macrophages (p<0.001). Placental malaria was associated with a threefold increase in the percentage of M2 maternal macrophages (19.2% vs 6.4%, p=0.01). Primigravidas showed a significant decrease in the Hofbauer cell M2-percentage in placental malaria (92.7% vs. 97.0%, p=0.04), which was predictive of infant birth weight (b=0.08 kg increase in birth weight per % increase in M2 Hofbauer cells, p=0.001). There was no association between maternal macrophage response and infant birth weights. CONCLUSIONS: Placentas with malarial infection had increased numbers of fetal Hofbauer cells in the villous stroma and maternal macrophages in the intervillous space. In primigravidas, decreased anti-inflammatory M2-type Hofbauer cells were predictive of lower birth weight. M2-type maternal macrophages were increased in placental malaria, but there was no association with gravidity or birth weight. These results suggested a protective role of M2 Hofbauer cells in fetal growth restriction.