A comparison of the diagnostic utility of the sFlt-1/PlGF ratio versus PlGF alone for the detection of preeclampsia/HELLP syndrome

Abstract

Objective: The Elecsys^® immunoassay sFlt-1/PlGF ratio and the Triage^® PlGF assay were compared (in a prospective, multicenter, case-control study) for diagnosis of preeclampsia/hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. Methods: Women in European perinatal care centers with singleton pregnancies were enrolled: 178 cases had confirmed preeclampsia and 391 controls had normal outcome. Patients in the preeclampsia/HELLP syndrome group were matched pairwise by gestational week to healthy controls (1:2). Maternal blood samples were analyzed using (a) fully automated Elecsys PlGF and Elecsys sFlt-1 immunoassays with two cutoffs (early-onset [<34 weeks] ≤33, ≥85; late-onset [≥34 weeks] ≤33, ≥110), and (b) Triage PlGF immunoassay (single cutoff). Diagnostic performance and utility were assessed. Results: Respectively, 83 and 95 women had early-onset or late-onset preeclampsia/HELLP syndrome. The overall diagnostic performance of the Elecsys immunoassay sFlt-1/PlGF ratio (area under the curve [AUC] 0.941) was higher than for Triage PlGF (AUC 0.917). The Elecsys immunoassay sFlt-1/PlGF ratio sensitivity and specificity was: 94.0% (95% confidence interval [CI] 86.5–98.0) and 99.4% (95% CI: 96.8–99.9) for early-onset preeclampsia; and 89.5% (95% CI: 81.5–94.8) and 95.4% (95% CI: 91.7–97.8) for late-onset preeclampsia. The Triage assay sensitivity and specificity was: 96.4% (95% CI: 89.8–99.3) and 88.5% (95% CI: 82.8–92.8) (early-onset); and 90.5% (95% CI: 83–96) and 64.5% (95% CI: 57.8–70.9) (late onset). Conclusions: The fully automated Elecsys immunoassay sFlt-1/PlGF ratio provides improved diagnostic utility over the Triage PlGF assay with improved specificity for the clinical management of pregnant women with suspected preeclampsia/HELLP syndrome.

KEYWORDS:

• Diagnosis
• HELLP syndrome
• placental growth factor (PlGF)
• preeclampsia
• soluble fms-like tyrosine kinase-1 (sFlt-1)

Acknowledgments

The authors would like to thank Christoph Ehret for his statistical input and for his work on the statistical analysis plan and Michael Pfeffer for useful discussions on the manuscript content, both from Roche Diagnostics GmbH, Penzberg, Germany. An author, Carina Dinkel, has carried out the statistical analyses described in this article. ELECSYS and COBAS are trademarks of Roche.

Declaration of interest

MH and MG are employees of Roche Diagnostics International, Rotkreuz, Switzerland. BD and CD are employees of Roche Diagnostics GmbH, Penzberg, Germany. HS has worked as an advisor for Roche Diagnostics and has received fees for lecturing. SV has received grants from and acted as a consultant for Roche Diagnostics, and acted as a consultant for ThermoFisher. WK, PW, BS, and TM are employees of Bioscientia GmbH, contracted by Roche Diagnostics. LD has no conflicts of interest.

Funding

The study was sponsored by Roche Diagnostics, who were involved in the study design, data collection, statistical analysis, and interpretation of data.Third-party writing assistance under the direction of the authors was provided by Martin Quinn, PhD, and Emma McConnell, PhD, both from Gardiner-Caldwell Communications (Macclesfield, UK), and was funded by Roche Diagnostics.

Contribution to authorship

All authors were involved in the writing of the manuscript and all authors made the decision to submit for publication.

Additional information

Funding

The study was sponsored by Roche Diagnostics, who were involved in the study design, data collection, statistical analysis, and interpretation of data.