Early and late onset preeclampsia: Two sides of the same coin

Pre-eclampsia is caused by the placenta. Although its pathogenesis is not clear, a critical risk factor is inadequate antenatal care, because it can prevent most of the secondary complications of the disorder. Pre-eclampsia is clinically defined by the secondary features of a primary placental disorder. There are probably several subtypes of preeclampsia of which early (EO-PE) and late onset disease (LO-PE) are the best known. These are classified by the time of delivery- EO-PE, delivered before 34 weeks and LO-PE, after 37 weeks; while intermediate onset disease (34–37ẇeeks) is a mixture of both types. One of the major differences is that EO-PE is usually complicated by intrauterine growth restriction (IUGR) while LO-PE is not. Another difference is that there is clear placental pathology with EO-PE while LO-PE placentas are usually normal to routine clinicopathological examination. The pathology of EO-PE comprises lesions of uteroplacental malperfusion. These are associated with maladaptation of the uteroplacental spiral arteries in early pregnancy (8–18 weeks, poor placentation) such that they are too small and too contractile to sustain the non-pulsatile, high volume, low pressure flow needed by the third trimester placenta. The result is oxidative stress and even infarction that damage placental tissue. The spiral arteries may also be obstructed by acute atherosis and atherosclerosis-like lesion that causes arterial thrombosis which underlies the infarctions. The surface syncytiotrophoblast layer, in direct contact with maternal blood, appears to be particularly vulnerable to damage. It is also the source of 'pre-eclampsia biomarkers' such as sFlt-1 or placental growth factor (PlGF). It will be explained why these are, in fact, markers of syncytiotrophoblast damage. Changes in the circulating sFlt-1 and PlGF levels at term indicate that syncytiotrophoblast damage is an increasing feature of normal pregnancy. Moreover the pathology, visible only to electron microscopy reveals widespread syncytiotrophoblast damage. Evidence is presented that this results from diffuse placental hypoxia, which develops as the placenta outgrows the capacity of the uterus and its vasculature to support the increasing demands of the term placenta, Hence EO-PE and LO-PE both result from the same problem, malperfusion, which has very different causes.