Angiogenic biomarkers in triage and risk for preeclampsia with severe features

Abstract

There is an urgent need for biomarkers that can help stratify women with suspected preeclampsia (PE) for the subsequent appearance of PE with severe features (sPE), to improve risk assessment and direct monitoring related to complications of sPE. Elevated levels of circulating anti-angiogenic factors like soluble fms-like tyrosine kinase 1 (sFlt1) and decreased free levels of pro-angiogenic factors such as placental growth factor (PlGF) are associated with adverse outcomes related to preeclampsia (PE). Here, we report in a single-center prospective study (N = 402) that plasma levels of these circulating angiogenic markers predict sPE within two weeks among women presenting with suspected PE in the preterm period (<37 weeks). sFlt1/PlGF ratio of >38 at the triage visit had a positive predictive value (PPV) of 47% and a negative predictive value (NPV) of 98% for the presence of sPE within 2 weeks. Among patients presenting <34 weeks, the PPV for sPE improved to 65% with NPV of 98%. sFlt1/PlGF ratio >85, had a PPV of 59% in all patients and 74% among patients presenting <34 weeks for the presence of sPE within 2 weeks. When we restricted the analysis to hospitalized patients, PPVs were 58% and 63% in all patients and 73% and 77% for patients presenting <34 weeks for plasma sFlt1/PlGF cutoff >38 and >85 respectively. Clinical trials are needed to evaluate whether risk stratification with angiogenic biomarkers in patients with suspected PE will lead to improved maternal and fetal outcomes among women at risk for severe disease.