Fetal responses during placental malaria modify the risk of low birth weight

Inflammation during placental malaria (PM) is associated with low birth weight (LBW), especially during the first pregnancy, but the relative contribution of maternal or fetal factors that mediate this effect remains unclear and the role of gamma interferon (IFN-gamma) has been controversial. We examined the relationship of maternal and cord plasma levels of IFN-gamma, tumor necrosis factor alpha, interleukin-10, ferritin, and leptin to birth weight for Tanzanian women delivering in an area where there is a high rate of malaria transmission. The placental levels of inflammatory cytokines, including IFN-gamma, increased significantly during PM in primigravid and multigravid women but not in secundigravid women. PM also increased maternal peripheral levels of all inflammatory markers except IFN-gamma but had strikingly little effect on cord levels of these proteins. In a multivariate analysis, placental IFN-gamma was negatively associated (P = 0.01) and cord ferritin was positively associated (P < 0.0001) with birth weight in infected (PM-positive [PM+]) first-time mothers. This relationship was not observed in other mothers, consistent with the epidemiology of PM and disease. Cord leptin had a strong positive relationship with birth weight in offspring of PM-negative women (P = 0.02 to P < 0.0001) but not in offspring of PM+ women (all differences were not significant) in the three gravidity groups. The results confirmed that placental IFN-gamma is related to LBW due to PM during first pregnancies and suggest that fetal ferritin plays a protective role. Because fetal cells are a source of placental IFN-gamma and cord ferritin, the fetal response to PM may modify the risk of LBW.