Uteroplacental vascular insufficiency. Extravillous cytotrophoblasts are less successful in invading the maternal decidua and may be removed by the maternal immune system (1). Consequently the distal spiral arteries are narrower (2) and diseased, accompanied by atherosis or local fibrin deposition (3) and reduced endovascular invasion (4). Hypoxia or hypoxia-reoxygenation injury (5) has direct effects on the villous trophoblast compartment, reducing syncytial fusion (6) that may trigger the formation of syncytial knots (7). These accumulate but may fragment and shed into maternal blood (8), whereas areas deficient in syncytial fusion may exhibit focal necrosis (9).