Pre-eclampsia as a ‘Three Stage Problem’—A Workshop Report

Abstract

This workshop, held in Leipzig (Germany) on 22 September 2003, was organized to link new aspects of causative factors for pre-eclampsia to possible clinical consequences. Since aetiology and pathogenesis of pre-eclampsia are still unclear, basic pre-eclampsia research has been focused on early trophoblast development as well as maternal endothelial dysfunction as relevant factors. However, the increased knowledge of the recent past in terms of the cause of pre-eclampsia and the pathophysiological link to the syndrome has not substantially improved the opportunities for risk assessment, early prediction, and causal therapy of pre-eclampsia. At present, new aspects of trophoblast function, the role of peptide systems, and novel genetic and endocrine studies will hopefully facilitate future options for a better understanding and treatment of this pregnancy complication. The aim of this workshop was to provide an overview on some of these novel and interesting aspects of pre-eclampsia. H. Stepan demonstrated that pre-eclampsia can nowadays be understood as a ‘three-stage problem’, whereby each trimenon generates one so far unsolved problem. Stage one in the first trimester is the unknown origin of the disease. An impaired trophoblast invasion is thought to be the central factor regarding the aetiology of pre-eclampsia. However, the evidence that the early disturbance of placental development is indeed causative is still lacking. Moreover, the role of factors like hypoxia and apoptosis is not as clear as once thought. For instance, new data show decreased apoptosis in pre-eclamptic placentae and contradict to the established opinion that placental apoptosis is increased in pregnancies with pre-eclampsia and IUGR. In the second trimenon, a pathological uterine perfusion raises the problem of stage two. Easily measurable by Doppler sonography, the impaired uterine perfusion as a sign of high impedance within the uteroplacental bed has a low positive predictive value since only 35 per cent of the afflicted women develop pregnancy complication later on. Furthermore, this method for the identification of women at risk is not able to predict which clinical manifestation as a result of placental insufficiency (pre-eclampsia, IUGR, HELLP syndrome) will develop. Thus, additional markers are needed that can improve the specificity of uteroplacental perfusion and can be used in clinical practice as an adjunct to sonography. The problem at ‘stage three’ describes pre-eclampsia as a syndrome with the global maternal endothelial damage as the central pathophysiological feature. Since the number of altered markers in maternal plasma as well as placenta is enormous and various metabolic, endocrine and neuro-vegetative axes are influenced, it is difficult at this stage of the disease to