Early disturbed placental ischemia and hypoxia creates immune alteration and vascular disorder causing preeclampsia.

Preterm preeclampsia (PE) remains a leading cause of maternal death and perinatal morbidity. The pathophysiological process that underlies PE has been proposed to occur in two episodes, the first is a reduced placental perfusion and then the maternal clinical syndrome. Placental ischemia/hypoxia is believed to result in the release of a variety of placental factors such as cytokines including TNF-α and interleukin 6, activated circulating immune cells and autoantibodies that have profound effects on blood flow and arterial pressure regulation. PE is also associated with decreased formation of vasodilators such as nitric oxide and prostacyclin. It is accompanied by widespread maternal vascular dysfunction and a chronic inflammatory response. Additionally, anti-angiogenic peptides are released, inhibiting vascular remodeling essential for increased blood flow to the growing uteroplacental unit. Although these factors accompany the clinical syndrome of PE, it is suggested that they are secondary to the maternal decrease in placental blood flow. Experimental evidence has demonstrated the importance of these soluble factors to increase blood pressure and stimulate the production of such anti-angiogenic factors, thereby eliciting a vicious cycle existing within the maternal vasculature as well as within the placental unit. These alterations in vascular function not only lead to hypertension but to multi-organ dysfunction. The quantitative importance of the various endothelial and humoral factors that mediate vascular dysfunction and hypertension during PE remains to be elucidated.