Pathogenesis of preeclampsia: a comprehensive model

The objective of this review was to provide a comprehensive and practical concept on the pathogenesis of preeclampsia on the basis of the currently available scientific evidence. A MEDLINE search was performed of English-language articles published between 1966 and 1997, supplemented with references cited in relevant research articles. Using our data sources, we developed a scheme describing the sequence of events between implantation and the time of manifest clinical disease characterized by generalized endothelial cell dysfunction. A yet unidentified toxic circulating factor released by the ischemic placenta, is held responsible for the impaired endothelial cell function. Particularly, epidemiological studies point to a concept in which immune maladaptation to the fetal allograft plays a key role in causing defective placentation leading to placental ischaemia. The incidence of preeclampsia in sisters and daughters of women who had had preeclampsia is raised. Disease states with vascular involvement, like chronic hypertension and diabetes mellites, are associated with an increased risk for preeclampsia. Recently subclinical abnormalities in hemostasis, metabolism and volume homeostasis have been described in patients with a history of preeclampsia. Placental ischemia secondary to defective placentation, a prerequisite for the development of preeclampsia, has a multifactorial origin consisting of three major components: immune maladaptation, genetic predisposition, and vascular mediated factors. Probably, a summation of these factors will determine whether a pregnant woman is to develop the syndrome. The recently described subclinical abnormalities in hemostasis, metabolism, and vascular function in patients with a history of preeclampsia might give the clinician the opportunity to reduce the recurrence risk by pharmacotherapeutic intervention.