Absence of Association Between Sickle Trait Hemoglobin and Placental Malaria Outcomes

Heterozygous hemoglobin S (HbAS), or sickle trait, protects children from life-threatening falciparum malaria, potentially by attenuating binding of Plasmodium-infected red blood cells (iRBCs) to extracellular ligands. Such binding is central to the pathogenesis of placental malaria (PM). We hypothesized that HbAS would be associated with reduced risks of PM and low birth weight (LBW). We tested this hypothesis in 850 delivering women in southern Malawi. Parasites were detected by polymerase chain reaction in placental and peripheral blood, and placentae were scored histologically for PM. The prevalence of HbAS was 3.7%, and 11.2% of infants were LBW (< 2,500 g). The prevalence of Plasmodium falciparum was 12.7% in placental and 8.5% in peripheral blood; 24.4% of placentae demonstrated histological evidence of P. falciparum. HbAS was not associated with reduced prevalence of P. falciparum in placental (odds ratio [OR]: 1.27, 95% confidence interval [CI]: 0.50–3.23, P = 0.61) or peripheral blood (OR: 2.53, 95% CI: 1.08–2.54, P = 0.03), prevalence of histological PM (OR: 0.97, 95% CI: 0.40–2.34, P = 0.95), or prevalence of LBW (OR: 0.82, 95% CI: 0.24–2.73, P = 0.74). Mean (standard deviation) birth weights of infants born to HbAS (2,947 g [563]) and, homozygous hemoglobin A (2,991 g [465]) mothers were similar. Across a range of parasitologic, clinical, and histologic outcomes, HbAS did not confer protection from PM or its adverse effects