Plasmodium falciparum malaria frequently infects the placenta of malaria-expose pregnant women, and may cause fetal growth restriction, preterm delivery, miscarriage and stillbirth. Close to term, chronic placental infection, the accumulation of parasitized erythrocytes accompanied by deposits of malaria pigment and maternal immune cells in the intervillous spaces, is strongly associated with poor outcomes, particularly fetal growth restriction. Two things are less clear: the mechanisms by which these later infections affect fetal growth and development; and the consequences of infection earlier in the pregnancy, during placental development, for fetal growth.

Recently our laboratory has begun to perform ex vivo and in vitro studies, using clinical samples and model systems, to identify some of the mechanisms underlying growth restriction. Sera from pregnant women from PNG with malaria (but not uninfected women) inhibited the invasion and migration of placental cell lines, and contained elevated levels of growth-inhibitory hormones and cytokines, suggesting a plausible mechanism by which malaria could interfere with placental development.

At delivery, our recent work shows that placental malaria infection associated with inflammation interferes with transfer of amino acids and glucose across the placenta. Transcription of the amino acid transporters SNAT-1 and SNAT-2 was decreased by malaria in placental tissue and in a model system, and cord blood amino acid levels were dysregulated.

Recent clinical studies, and mathematical models, suggest that malaria infection in late first and early second trimester is associated with low birth weight delivery, and together these findings suggest that pregnant women require protection from malaria from earlier stages of pregnancy than is currently recommended. To prevent adverse outcomes due to malaria in pregnancy, it may be necessary to prevent infections that result in impairments in placentation, in addition to controlling infection that results in excessive maternal immune response near term.