Predicting pre‐eclampsia: 100 years of trying and failing

ERIC JAUNIAUX, SCIENTIFIC EDITOR, BJOG, PROFESSOR IN OBSTETRICS AND FETAL MEDICINE, FRCOG, INSTITUTE FOR WOMEN’S HEALTH, UNIVERSITY COLLEGE LONDON, LONDON, UK, AND PHILIP STEER, FRCOG, EMERITUS EDITOR BJOG, DEPARTMENT OF OBSTETRICS, IMPERIAL COLLEGE LONDON, LONDON, UK The symptoms of eclampsia, a Greek word meaning ‘lightning’, have been known to medicine since Hippocrates (460–370 BC), but it was only in the 18th century that doctors made a distinction between eclampsia and epilepsy (Bell MJ. J Obstet Gynecol Neonatal Nurs 2010;39:510–8). Eclampsia/preeclampsia results from a disorder of placentation characterised by the insufficient transformation of the spiral arteries at the level of the placental bed. The trophoblastic invasion is sufficient to allow early pregnancy phases of placentation, but is too shallow for the complete transformation of the arterial uteroplacental circulation. Heritable paternal imprinting of the genome is necessary for normal trophoblast development. Several large cohort studies have identified paternal single nucleotide polymorphisms (SNPs) that have strong associations with pre-eclampsia, in particular in the paternally expressed genes affecting placentation (Dekker G et al. J Reprod Immuno 2011;89:126–32). We have proposed that eclampsia/pre-eclampsia is a three-stage disorder, with the primary pathology being an excessive or atypical maternal immune response, which impairs placentation leading to placental chronic oxidative stress, and subsequently to diffuse maternal endothelial cell dysfunction (Jauniaux E et al. Hum Reprod 2006;12:747–55). For centuries the diagnosis of eclampsia or toxaemia was exclusively based on the presence of maternal convulsions, before or after delivery. Other symptoms such as headache, hypogastric pain, temporary loss of vision, and severe oedema were recognised by the mid 19th century, suggesting that a prodromal stage existed before eclampsia. Pierre Rayer (1793–1867), a French physician, was the first to describe proteinuria in eclamptic women and John Lever (1811–1859), an English physician, is credited with being the first to have shown that eclampsiaassociated proteinuria was specific to the disease (Bell MJ. J Obstet Gynecol Neonatal Nurs 2010;39:510–8). Modern blood pressure measurement became available when Nikolai Korotkov (1874–1920), a Russian vascular surgeon, discovered the difference between systolic and diastolic blood pressure. Urine analysis and blood pressure measurements came into use at the beginning of the 20 century (Corbett D BJOG 1913;23:227–37). These discoveries made it possible to identify women at risk of eclamptic convulsion, and the concept of pre-eclampsia started to appear in modern medical literature.