Impact of Immunoassay Selection on the sFlt-1/PlGF Ratio and Preeclampsia Risk Classification.

Abstract

Background: The soluble fms-like tyrosine kinase-1/ placental growth factor (sFlt-1/PlGF) ratio is widely used to aid in preeclampsia (PE) prognosis. Many laboratories apply cutoffs derived from the PRediction of short-term Outcome in preGNant wOmen with Suspected preeclampsIa Study (PROGNOSIS) using Elecsys results. However, differences between immunoassays and lack of international standardization introduce variability in sFlt-1/PlGF values and cutoffs, potentially affecting clinical interpretation. This study compared Elecsys and Kryptor immunoassays for sFlt-1 and PlGF and assessed their impact and the best cutoff for their ratio in PE risk classification.

Methods: We compared Elecsys and Kryptor immunoassays in 160 samples from pregnant women with suspected PE. Correlation, receiver operating characteristic (ROC) performance (area under the curve [AUC]), and concordance across risk categories (low/intermediate/high) were assessed using Elecsys-based PROGNOSIS study cutoffs and a Kryptor-specific threshold.

Results: Kryptor yielded significantly lower PlGF and sFlt-1 concentrations than Elecsys (medians: 103.5 ng/L vs 146.3 ng/L and 3199 ng/L vs 4034 ng/L; both P < 0.001). Conversely, sFlt-1/PlGF ratios were higher with Kryptor (31 vs 25; P < 0.001). Diagnostic accuracy was comparable (AUC: Elecsys 0.809; Kryptor 0.810). Applying Elecsys cutoffs to Kryptor results shifted risk categorization, with Kryptor classifying fewer women as low risk (54.4%) compared with Elecsys (58.2%), and more women as high risk (24.3% vs 18.1%). Overall concordance was high (85%; κ = 0.750), but among Elecsys-classified intermediate-risk samples, Kryptor agreed in only 63.2% and 31.6% were upgraded to high risk, reflecting Kryptor's tendency toward higher ratios.

Conclusions: Elecsys and Kryptor show similar discriminative performance; however, immunoassay selection can alter PE risk stratification, particularly for intermediate risk cases. Method-specific thresholds are essential to avoid misclassification and optimize clinical decisions.