Malaria in pregnancy at the frontline: a delicate balance

Malaria during pregnancy continues to compromise maternal, fetal, and subsequently infant health. This burden has increased in Africa, though it has decreased elsewhere. Here, we provide a concise review of recent findings on malaria in pregnancy, addressing pathogenesis, immunity, offspring outcomes, and interventions. Placental alterations and inflammation accompanying Plasmodium infection result in maternal morbidity and adverse birth outcomes, with new findings indicating antenatal infection affects infant immune and neurocognitive development. Adverse outcomes from placental infection reduce over successive pregnancies, but the drivers of this protection have been challenging to uncover. Despite parasite resistance to sulfadoxine-pyrimethamine (SP), it still helps improve birth weight as an intermittent preventive treatment in pregnancy. Dihydroartemisinin-piperaquine, though more effective against parasitemia, does not improve birth outcomes when used alone or in combination with SP. Interventions targeting first-trimester infections, blood-stage parasites, and vaccines that prime defences in primigravidae would be optimal for controlling malaria in pregnancy. • VAR2CSA antibodies that inhibit CSA adhesion seem crucial for protection from PM. • DP is a better antimalarial than SP, but it fails to improve birth outcomes. • Antibody glycosylation may be an important driver of protection in PM. • Malaria in pregnancy modifies infant and fetal immune development. • Inflammatory regulation and disease severity in pregnancy may differ by species.