A Step-Wedge in the Biochemical Diagnosis of Preeclampsia

Abstract

Preeclampsia, a hypertensive disorder of pregnancy, is one of the leading causes of maternal and neonatal morbidity and mortality worldwide. Among the reasons for the great global burden of disease is the poor predictive value of high blood pressure and proteinuria (traditional markers for the disease) for related adverse outcomes (1). Angiogenic biomarkers developed and studied during the past decade are widely recognized as clinically sensitive and specific biomarkers, with excellent predictive values during the third trimester that complement and improve upon clinical signs and symptoms (2). Normally produced in pregnancy, soluble FMS-like tyrosine kinase (sFLT1) is a placentally produced, antiangiogenic protein that mitigates rapidly progressing placental angiogenesis driven by proangiogenic proteins—placental growth factor (PlGF) and vascular endothelial growth factor—in the latter third of gestation. Preeclampsia is characterized by enhanced production of placental sFLT1, which in turn binds to PlGF, causing the free concentration of serum PlGF to fall. Increased circulating sFLT1 and decreased free PlGF antedate the onset of preeclamptic signs and symptoms, allowing for accurate and minimally invasive risk assessment of the systemic vascular damage that characterizes preeclampsia (2). Furthermore, angiogenic biomarkers can be used to differentiate preeclampsia from mimickers of disease, such as chronic hypertension, gestational hypertension, and chronic kidney disease (2). Despite the opportunity for early identification of disease before the onset of signs and symptoms, funding bodies have been reluctant to invest in the head-to-head comparisons of angiogenic biomarkers vs traditional factors, leading to a …