New developments in pre-eclampsia

Abstract

It is quite clear that pre-eclampsia is not simply pregnancy-induced hypertension; rather, it is a multisystem disease with pathophysiological changes secondary to reduced organ perfusion. This reduction can be explained by vasospasm secondary to increased sensitivity of the vasculature to usual circulating pressors, and vascular occlusion secondary to activation of the coagulation cascade. Although pre-eclampsia becomes clinically evident late in pregnancy, pathological and pathophysiological changes antedate the clinical syndrome by weeks to months. The syndrome occurs only in pregnancy and is cured by the removal of fetoplacental tissues.Based on these findings, we have proposed that the inciting pathophysiological change of preeclampsia is reduced trophoblastic perfusion, which produces an agent that perturbs endothelial cells. The altered endothelial functions associated with this insult increase sensitivity to pressors, activate the coagulation cascade and produce the clinical and pathological findings of preeclampsia. Although we feel this hypothesis could explain pre-eclampsia, it is possible that its major value will be to stimulate others to approach this disorder by considering all facets of its pathophysiology rather than merely its hypertensive component.The appreciation of pre-eclampsia as a disease present from early pregnancy and the potential role of vasodilator prostaglandins have already stimulated therapeutic trials of aspirin in women at very high risk with encouraging results. At present, information is insufficient to determine the risk/benefit ratio of this therapy in lower risk patients, and aspirin therapy should not be used in these women. Another potential modification of therapy, the substitution of phenytoin for magnesium sulphate, does not seem warranted on the basis of either currently available data or on theoretical grounds.Fruitful directions for research in the near future will be the explanation of the abnormal trophoblastic invasion of pre-eclampsia and the determination of how reduced perfusion translates into a multisystem disease. In addition, aspirin therapy or other potential prophylactic therapies would be greatly aided by the development of new tests with reasonable positive predictive values, in order to identify preeclampsia prior to clinically evident disease.