During pregnancy, Plasmodium falciparum-infected erythrocytes (IE) sequester in the placenta where they induce pathology and increase the risk of low-birth-weight (LBW) babies. The innate immune mediator, mannose-binding lectin (MBL), enhances phagocytosis of pathogens. Since MBL is reported to bind to IE, we hypothesized that it might aid in clearance of IE from the placenta, thereby reducing the risk of LBW babies. To test this hypothesis, molecular genotyping was used to detect polymorphisms at codon 57 (A/C) in exon 1 of MBL2 in 401 pregnant Cameroonian women, with or without placental malaria, who had LBW and normal-weight babies. Polymorphisms in the promoter region at positions ؊550 (H/L), ؊221 (X/Y), and ؉4 (P/Q) were also determined, and plasma MBL levels were measured during pregnancy and at delivery. The expected correlation between genotype and plasma MBL levels was confirmed. However, asymptomatic infections were not associated with an increase in MBL levels in the peripheral blood, and MBL levels were similar in the placental and cord blood of women with or without placental malaria at delivery. There was no evidence that MBL levels at delivery were associated with malaria-related poor pregnancy outcomes. Women with the LXPA haplotype, however, were more likely to have LBW babies, but the risk was not related to malaria. These results do not support the hypothesis that MBL aids in the clearance of parasites from the placenta but suggest that Cameroonian women with LXPA are at risk of having LBW babies due to other causes.Women who become infected with Plasmodium falciparum during pregnancy are at an increased risk of anemia and poor pregnancy outcomes (5, 25). One reason for these complications is that P. falciparum-infected erythrocytes (IE) sequester in the intervillous space (IVS) of the placenta (9). As a result, monocytes and macrophages are attracted to the IVS (30, 36), where they stimulate an inflammatory response, produce placental pathology (42), and increase the risk of low-birth-weight (LBW) babies due to intrauterine growth reduction and premature deliveries (reviewed in reference 6). Thus, elimination of IE from the IVS is of great importance.Little is known about the role of innate immune cells and factors in eliminating IE from the IVS. An acute-phase protein that might be important is mannose-binding lectin (MBL), since it promotes opsonophagocytosis and activates the MBL pathway upon binding to oligosaccharides on pathogens (12,17). MBL is reported to bind to the surface of IE and possibly merozoites, although the ligand involved remains undefined (10, 15). In addition, MBL2 genetic deficiencies in children are associated with severe malaria (4, 11). Therefore, it is possible that MBL aids in eliminating IE by enhancing phagocytosis, leading to reduced pathology and risk of LBW babies.Plasma levels of MBL are influenced by three functional single nucleotide polymorphisms (SNPs) in exon 1 of the MBL2 gene at codons 52, 54, and 57 (D, B, and C, respectively) (18,20,21,35). These SNP...