Preeclampsia and eclampsia: the conceptual evolution of a syndrome

Abstract

Preeclampsia, one of the most enigmatic complications of pregnancy, is considered a pregnancy-specific disorder caused by the placenta and cured only by delivery. This article traces the condition from its origin—once thought to be a disease of the central nervous system, recognized by the occurrence of seizures (ie eclampsia)—to the present time when preeclampsia is conceptualized primarily as a vascular disorder. We review the epidemiologic data that led to the recommendation to use diastolic hypertension and proteinuria as diagnostic criteria, given that their combined presence was associated with an increased risk of fetal death and the birth of small-for-gestational-age neonates. However, preeclampsia is a multi-systemic disorder with protean manifestations, and the condition can be present even in the absence of hypertension and proteinuria. Toxin(s) that gain access to the maternal circulation have been proposed to mediate the clinical manifestations—hence, the term “toxemia of pregnancy,” which was used for several decades. The search for putative toxins has challenged investigators for more than a century, and a growing body of evidence suggests that products of an ischemic or a stressed placenta are responsible for the vascular changes that characterize the syndrome. The discovery that the placenta can produce anti-angiogenic factors, which regulate endothelial cell function and induce intravascular inflammation, has been a major step forward in the understanding of preeclampsia. We view the release of anti-angiogenic factors by the placenta as an adaptive response to improve uterine perfusion by modulating endothelial function and maternal blood pressure. However, this homeostatic response can become maladaptive and lead to the damage of target organs during pregnancy or the postpartum period. Early-onset preeclampsia has many features in common with atherosclerosis, while late-onset disease appears to result from a mismatch of fetal demands and maternal supply: in other words, a metabolic crisis. Preeclampsia, as it is understood today, is essentially vascular dysfunction unmasked, or caused, by pregnancy that results in a multi-systemic disorder. A subset of patients diagnosed with preeclampsia are at greater risk for the subsequent development of hypertension, ischemic heart diseases, heart failure, vascular dementia, and end-stage renal disease. However, these adverse events may be the result of a preexisting vascular pathologic process; it is not known if the occurrence of preeclampsia by itself increases the baseline risk. The understanding of preeclampsia is a healthcare priority.