What causes pre-eclampsia?

Pre-eclampsia remains a leading cause of maternal and fetal morbidity and mortality. Despite extensive research, the mechanisms that cause pre-eclampsia are unknown and it has been considered to be the 'disease of theories'. Hippocrates wrote in one of his Aphorisms that 'convulsions take place from either repletion or depletion'. Since then, obstetricians have been divided on the question of which factor accounted for the convulsions observed during childbirth. Some considered that a sudden reduction in intra-abdominal pressure at delivery led to a pooling of blood diverted from the brain, causing collapse of the cerebral blood vessels and convulsions. Others postulated that cerebral congestion, secondary to compression of the abdominal organs by the large uterus, diverted blood to the brain, causing eclamptic convulsions. It is the purpose of this review to examine those theories about the cause of pre-eclampsia for which modern evidence is available. At present, it is believed that the pathological chain of events leading to pre-eclampsia is scheduled in two steps: an absolute or relative placental ischaemia is followed by a diffuse endothelial cell activation, which causes the clinical features of the disease.