Clinical Validation of the sFlt-1:PlGF Ratio as a Biomarker for Preeclampsia Diagnosis in a High-Risk Obstetrics Unit
Jessica Miller, Victoria Higgins, Nir Melamed, Michelle Hladunewich, Liyan Ma, Paul S. F. Yip, Lei Fu
Abstract
BACKGROUND: Preeclampsia is a multisystem disorder defined by new onset of hypertension with proteinuria after 20 weeks gestation. In part due to dysregulation of pro-angiogenic factors (e.g., placental growth factor [PlGF]) and anti-angiogenic factors (e.g., soluble fms-like tyrosine kinase 1 [sFlt-1]), preeclampsia results in decreased placental perfusion. An increased sFlt-1:PlGF ratio is associated with increased risk of preeclampsia. In this study, we evaluated sFlt-1:PlGF cutoffs and evaluated the clinical performance of sFlt-1:PlGF for predicting preeclampsia. METHODS: sFlt-1:PlGF results from 130 pregnant females with clinical suspicion of preeclampsia were used to evaluate the diagnostic accuracy of different sFlt-1:PlGF cutoffs and to compare the clinical performance of sFlt-1:PlGF to traditional preeclampsia markers (proteinuria and hypertension). Serum sFlt-1 and PlGF were measured using Elecsys immunoassays (Roche Diagnostics) and preeclampsia diagnosis was verified by expert chart review. RESULTS: A sFlt-1:PlGF cutoff of >38 yielded the greatest diagnostic accuracy of 90.8% (95% CI, 85.8%-95.7%). Using a cutoff of >38, sFlt-1:PlGF exhibited a greater diagnostic accuracy than traditionally used parameters such as new or worsening proteinuria or hypertension (71.9% and 68.6%, respectively). sFlt-1:PlGF >38 exhibited a negative predictive value (NPV) of 96.4% for rule-out of preeclampsia within 7 days, and a positive predictive value (PPV) of 84.8% for predicting preeclampsia within 28 days. CONCLUSIONS: Our study shows the superior clinical performance of sFlt-1:PlGF over hypertension and proteinuria alone to predict preeclampsia at a high-risk obstetrical unit.