Placental Malaria and Adverse Pregnancy Outcomes

Placental malaria is a specialised form of malaria in pregnancy characterised by the sequestration of Plasmodium-infected erythrocytes within the intervillous spaces of the placenta. This process triggers a local inflammatory response, known as intervillositis, and leads to structural damage of the trophoblastic barrier. The ensuing cascade involves release of pro- and anti-inflammatory cytokines, oxidative stress and dysregulation of key signalling pathways, notably mechanistic target of rapamycin (mTOR). Collectively these events compromise placental vasculature, nutrient transport and gas exchange. Clinically, placental malaria is associated with maternal anaemia, intrauterine growth restriction, low birth weight, preterm delivery and stillbirth. Both Plasmodium falciparum and P. vivax can induce placental pathology, though the former is most frequently implicated in severe outcomes. The global burden remains concentrated in malaria-endemic regions of sub-Saharan Africa, Southeast Asia and South America, where intermittent preventive treatment during pregnancy (IPTp) is standard but threatened by rising drug resistance. A clearer understanding of immunopathological mechanisms and placental dysfunction is needed to guide new interventions and safeguard maternal and neonatal health.

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Placental Malaria and Adverse Pregnancy Outcomes publication trend

The graph below shows the total number of articles in placental malaria and adverse pregnancy outcomes across all publications each year (not limited to Nature Index journals).

Technical terms

Sequestration: The adherence and accumulation of infected red blood cells within placental intervillous spaces, initiating local inflammation.

Intervillositis: A placental inflammatory response characterised by infiltration of maternal immune cells into intervillous spaces, often with elevated cytokines.

Syncytiotrophoblast: The outer multinucleated layer of the placental villi that mediates nutrient and gas exchange between mother and fetus.

mTOR signalling: A key intracellular pathway regulating cell growth and nutrient transport in the placenta; its inhibition during malaria impairs amino acid uptake.

System A amino acid transporters: Placental transport proteins responsible for sodium-dependent uptake of neutral amino acids essential for fetal development.

References

1. Phenotypic changes of γδ T cells in Plasmodium falciparum placental malaria and pregnancy outcomes in women at delivery in Cameroon. Frontiers in Immunology (2024).
2. Plasmodium falciparum alters the trophoblastic barrier and stroma villi organization of human placental villi explants. Malaria Journal (2024).
3. Inhibition of placental mTOR signaling provides a link between placental malaria and reduced birthweight. BMC Medicine (2017).