Preeclampsia: Updates in Pathogenesis, Definitions, and Guidelines

Abstract

Preeclampsia is becoming an increasingly common diagnosis in the developed world and remains a high cause of maternal and fetal morbidity and mortality in the developing world. Delay in childbearing in the developed world feeds into the risk factors associated with preeclampsia, which include older maternal age, obesity, and/or vascular diseases. Inadequate prenatal care partially explains the persistent high prevalence in the developing world. In this review, we begin by presenting the most recent concepts in the pathogenesis of preeclampsia. Upstream triggers of the well described angiogenic pathways, such as the heme oxygenase and hydrogen sulfide pathways, as well as the roles of autoantibodies, misfolded proteins, nitric oxide, and oxidative stress will be described. We also detail updated definitions, classification schema, and treatment targets of hypertensive disorders of pregnancy put forth by obstetric and hypertensive societies throughout the world. The shift has been made to view preeclampsia as a systemic disease with widespread endothelial damage and the potential to affect future cardiovascular diseases rather than a self-limited occurrence. At the very least, we now know that preeclampsia does not end with delivery of the placenta. We conclude by summarizing the latest strategies for prevention and treatment of preeclampsia. A better understanding of this entity will help in the care of at-risk women before delivery and for decades after.

Keywords: Cardiovascular Diseases; Humans; Pre-Eclampsia; Prevalence; VEGF; blood pressure; clinical hypertension; obesity; proteinuria; risk factors.

Figure 1.

Pathogenesis of preeclampsia: two-stage model. AT1-AA, autoantibodies to angiotensin receptor 1; COMT, catechol-O-methyltransferase; HTN, hypertension; LFT, liver function test; PlGF1, placental growth factor 1; PRES, posterior reversible encephalopathy syndrome; sEng, soluble endoglin; sFlt-1, soluble fms–like tyrosine kinase 1; sVEGFR1, soluble vascular endothelial growth factor receptor 1; VEGF, vascular endothelial growth factor. Reprinted from reference , with permission.