3-5% of all pregnancies are affected by preeclampsia, which is associated with multiple adverse maternal and fetal outcomes, including preterm birth and fetal growth restriction. Preeclampsia isone of the leading causes of maternal mortality, particularly in developing countries, and is responsible for over 60,000 maternal deaths annually. Preeclampsia is a multi-system disorder affecting maternal blood vessels (causing high blood pressure and vascular injury), kidneys, liver, the haematological system, brain (causing seizures, or eclampsia) and the fetoplacental unit (resulting in growth restriction).A better understanding of the pathophysiology of the disease as well as early prediction of preeclampsia are essential to allow close monitoring of women at risk, and timely intervention to reduce the burden of preeclampsia.
It is now widely accepted that the pathophysiology of preeclampsia can be attributed to two main processes: inadequate placentation and subsequent maternal endothelial dysfunction. In women with preeclampsia, there is shallow implantation of the placenta resulting in inadequate invasion and remodelling of the maternal uterine spiral arteries. This compromises placental perfusion and leads to fluctuations in oxygen delivery that predispose to oxidative stress. What is seen to be the disease is in fact the maternal response to placental stress. Placental oxidative stress provokes the release of anti-angiogenic factors such as soluble fms-like tyrosine kinase 1 (sFlt1) and soluble endoglin (sEng). These factors enter the maternal blood stream causing widespread vascular dysfunction and multi-system maternal organ injury.
In this presentation I will give a brief overview of the key discoveries in the pathogenesis of preeclampsia across the last 50 years, before focusing on our most recent findings, identifying novel contributors of impaired placentation and novel soluble placental factors that promote endothelial dysfunction. After all of this research what questions remain and why have we not yet found a cure?