Heterogeneous causes constituting the single syndrome of preeclampsia: a hypothesis and its implications

The cause of preeclampsia remains elusive in spite of many attempts to understand its biologic characteristics and to characterize its predictors. We suggest that there are distinct origins of preeclampsia, each with its own pathologic characteristics and natural history. One genesis is the result of reduced placental perfusion, which we will call placental, and another results from maternal disorders preexisting (but sometimes not evident before) pregnancy. These preexisting maternal disorders comprise predisposing factors for cardiovascular disease such as hypertension, renal disease, overweight, and diabetes. A critical review of the epidemiologic and pathologic literature is presented, which supports the hypothesis that preeclampsia is the result of heterogeneous causes. The implications of this hypothesis are discussed, particularly its impact on the development of rules to predict the occurrence of preeclampsia.