Clinical Outcomes of Submicroscopic Infections and Correlates of Protection of VAR2CSA Antibodies in a Longitudinal Study of Pregnant Women in Colombia

Background Malaria in pregnancy can cause serious adverse outcomes for the mother and the fetus. However, little is known about the effects of submicroscopic infections (SMIs) in pregnancy, particularly in areas where Plasmodium (P.) falciparum and P. vivax co-circulate. Methods A cohort of 187 pregnant women living in Puerto Libertador in Northwest Colombia was followed longitudinally from recruitment to delivery. Malaria was diagnosed by microscopy, RT-qPCR, and placental histopathology. Gestational age, hemoglobin concentration, VAR2CSA-specific IgG levels and adhesion-blocking antibodies were measured during pregnancy. Statistical analyses were performed to evaluate the impact of SMIs on birth weight and other delivery outcomes. Results Twenty-five percent of women (45/180) were positive for SMIs during pregnancy. Forty-seven percent of infections (21/45) were caused by P. falciparum , 33% by P. vivax , and 20% by mixed Plasmodium spp. Mixed infections of P. falciparum and P. vivax were associated with lower gestational age at delivery (p=0.0033), while other outcomes were normal. Over 60% of women had antibodies to VAR2CSA and there was no difference in antibody levels between those with SMIs or not. The anti-adhesion function of these antibodies was associated with protection from SMI-related anemia at delivery (p=0.0086). Conclusions SMIs occur frequently during pregnancy and while they were not associated with a decrease in birth weight, mixed infections of both P. falciparum and P. vivax were associated with significant risk of pre-term birth. We propose that the lack of adverse delivery outcomes is due to functional VAR2CSA antibodies that can protect pregnant women from SMI-related anemia.