Rule-in and rule-out of pre-eclampsia using DELFIA Xpress PlGF 1-2-3 and sFlt-1: PlGF ratio.

Abstract

The objective of this study was to explore and validate thresholds for Placental growth factor (PlGF) and soluble fms-like tyrosine-kinase 1 (s-Flt-1) (as s-Flt-1: PlGF ratio), to rule-in and rule-out disease in women with suspected pre-eclampsia, using DELFIA® Xpress PlGF1-2-3 and sFlt-1 assays. 369 samples from women with suspected or confirmed pre-eclampsia were analysed from a prospective cohort study. Serum PlGF and sFlt-1: PlGF were quantified using DELFIA® Xpress PlGF1-2-3 and DELFIA® Xpress sFlt-1 tests. Performances were evaluated at established and exploratory thresholds. Low PlGF concentration and sFlt-1: PlGF AUROC were compared. PlGF 1-2-3 concentration thresholds were confirmed to have high performance for rule-in (<50pg/ml) and rule-out (≥150pg/ml) pre-eclampsia within seven days (20-33+6 Weeks<50pg/ml: Negative predictive value (NPV) 90.7% (95% CI 83.9, 95.3); ≥150pg/ml: NPV 94.8% (95% CI 88.4, 98.3)) and 28days (20-33+6 Weeks<50pg/ml: Negative predictive value (NPV) 83.9% (95% CI 76.0, 90.0); ≥150pg/ml: NPV 92.8% (95% CI 85.7, 97.0)). Optimal sFlt-1: PlGF thresholds for rule-in were≥70 before 34weeks and≥90 after 34weeks, and<50 to rule-out pre-eclampsia. Low PlGF alone had comparable performance to sFlt-1: PlGF, but test performance for both was reduced in women with Kidney Disease. DELFIA® Xpress PlGF1-2-3 and sFlt-1 assays for pre-eclampsia rule-in and rule-out have comparable performance to other established assays, and could be an alternative for clinical use. Performance was not enhanced by use of sFlt-1: PlGF ratio, suggesting that PlGF alone could provide a cheaper alternative to dual biomarker testing.