Impact of PlGF immunoassay imprecision on preeclampsia risk assessment with the sFlt-1 to PlGF ratio.

Abstract

The US Food and Drug Administration recently approved the ratio of soluble FMS-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF) using the Thermo Fisher Scientific B·R·A·H·M·S KRYPTOR autoanalyzer-the first preeclampsia marker used for clinical testing. We evaluated the analytical precision of the sFlt-1 and PlGF assays, focusing on the effects of PlGF imprecision on the sFlt-1 to PlGF ratio interpretation and clinical reliability for preeclampsia risk assessment. We measured sFlt-1 and PlGF on the KRYPTOR instrument using a homogeneous sandwich fluoroimmunoassay. Between-day precision was assessed using 3 levels of commercial quality control (QC) materials and analyzed over 3 months. In all, 180 samples obtained from 161 hospitalized pregnant women were analyzed to assess the relationship between PlGF levels and the sFlt-1 to PlGF ratio. The sFlt-1 assay demonstrated good precision (coefficient of variation (s/x̄) × 100 [CV] = approximately 3.0%) across all QC levels, while the PlGF assay exhibited higher imprecision, particularly at low QC levels (CV = 7.7%-11.3%). Long-term QC monitoring revealed a downward drift in PlGF values, with improved stability after reagent lot changes. Despite higher imprecision at lower PlGF levels (23.1-34.7 ng/L), the clinical interpretation of the sFlt-1 to PlGF ratio remained robust because low PlGF consistently correlated with ratios well above the critical cutoff of 40. Despite the suboptimal precision observed at low QC levels and potential drifts in PlGF results, the sFlt-1 to PlGF ratio remains a reliable tool for preeclampsia risk assessment. This study highlights the need for critical evaluation of analytical performance beyond FDA approval and the importance of assessing the potential impact of assay imprecision on patient care for individual biomarkers.