PROGNOSIS; PlGF; angiogenic factors; pre-eclampsia; retesting; rule out; sFlt-1; sFlt-1/PlGF; Biomarkers; PGF protein, human; Placenta Growth Factor; Vascular Endothelial Growth Factor Receptor-1; Adult; Biomarkers/metabolism; Female; Fetus; Gestational Age; Humans; Placenta Growth Factor/blood; Pre-Eclampsia/blood; Pre-Eclampsia/diagnosis; Pre-Eclampsia/epidemiology; Pre-Eclampsia/mortality; Predictive Value of Tests; Pregnancy; Prenatal Diagnosis/methods; Prognosis; Prospective Studies; Retrospective Studies; Vascular Endothelial Growth Factor Receptor-1/blood; Prenatal Diagnosis; Radiological and Ultrasound Technology; Reproductive Medicine; Radiology, Nuclear Medicine and Imaging; Obstetrics and Gynecology; General Medicine
Abstract :
[en] [en] OBJECTIVES: The soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) ratio is generally elevated some time before and at the clinical onset of pre-eclampsia. The PROGNOSIS study validated a sFlt-1/PlGF ratio cut-off of ≤ 38 to rule out the onset of pre-eclampsia within 1 week of testing in women with suspected disease. The aim of this study was to assess the predictive value of the sFlt-1/PlGF ratio to rule out the onset of pre-eclampsia for up to 4 weeks, and to assess the value of repeat measurements.
METHODS: This was an exploratory post-hoc analysis of data from the PROGNOSIS study performed in pregnant women aged ≥ 18 years with suspected pre-eclampsia, who were at 24 + 0 to 36 + 6 weeks' gestation at their first clinic visit. Serum samples were collected at the first visit and weekly thereafter. sFlt-1 and PlGF levels were measured using Elecsys® sFlt-1 and PlGF immunoassays. Whether the sFlt-1/PlGF ratio cut-off of ≤ 38 used to rule out the onset of pre-eclampsia within 1 week could predict the absence of pre-eclampsia 2, 3, and 4 weeks post-baseline was assessed. The value of repeat sFlt-1/PlGF testing was assessed by examining the difference in sFlt-1/PlGF ratio 2 and 3 weeks after the first measurement in women with, and those without, pre-eclampsia or adverse fetal outcome.
RESULTS: On analysis of 550 women, sFlt-1/PlGF ratio ≤ 38 ruled out the onset of pre-eclampsia 2 and 3 weeks post-baseline with high negative predictive values (NPV) of 97.9% and 95.7%, respectively. The onset of pre-eclampsia within 4 weeks was ruled out with a high NPV (94.3%) and high sensitivity and specificity (66.2% and 83.1%, respectively). Compared with women who did not develop pre-eclampsia, those who developed pre-eclampsia had significantly larger median increases in sFlt-1/PlGF ratio at 2 weeks (∆, 31.22 vs 1.45; P < 0.001) and at 3 weeks (∆, 48.97 vs 2.39; P < 0.001) after their initial visit. Women who developed pre-eclampsia and/or adverse fetal outcome compared with those who did not had a significantly greater median increase in sFlt-1/PlGF ratio over the same period (∆, 21.22 vs 1.40; P < 0.001 at 2 weeks; ∆, 34.95 vs 2.30; P < 0.001 at 3 weeks).
CONCLUSION: The Elecsys® immunoassay sFlt-1/PlGF ratio can help to rule out the onset of pre-eclampsia for 4 weeks in women with suspected pre-eclampsia.
Disciplines :
Reproductive medicine (gynecology, andrology, obstetrics)
Author, co-author :
Zeisler, H; Department of Obstetrics and Gynecology, Medical University Vienna, Vienna, Austria
Llurba, E; Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain
Chantraine, Frédéric ; Centre Hospitalier Universitaire de Liège - CHU > > Service de gynécologie-obstétrique (CHR)
Vatish, M; University of Oxford, Oxford, UK
Staff, A C; Oslo University Hospital and University of Oslo, Oslo, Norway
Sennström, M; Karolinska University Hospital, Stockholm, Sweden
Olovsson, M; Uppsala University, Uppsala, Sweden
Brennecke, S P; Department of Obstetrics and Gynaecology, The University of Melbourne and Royal Women's Hospital, Melbourne, Australia
Stepan, H; Leipzig University, Leipzig, Germany
Allegranza, D; Roche Diagnostics International Ltd, Rotkreuz, Switzerland
Schoedl, M; Roche Diagnostics GmbH, Penzberg, Germany
We thank all the women who participated in the PROGNOSIS study, and the recruitment officers, midwives and midwifery staff who supported the study. A. C. Staff was the Principal Coordinating Investigator for the PROGNOSIS study. Roche Diagnostics sponsored this study. ELECSYS and COBAS are trademarks of Roche. Third-party writing assistance for this manuscript was provided by Abigail Robertson, PhD and Emma McConnell, PhD (Gardiner-Caldwell Communications) and was funded by Roche Diagnostics. H.Z. reports receiving lecture fees from Ferring and Roche Diagnostics and travel support from Ferring; E.L. reports receiving fees from Roche Diagnostics for lectures and serving on advisory boards; F.J.C. reports receiving fees from Roche Diagnostics for serving on advisory boards; M.V., M.Se. and S.P.B. report receiving lecture fees from Roche Diagnostics; H.S. reports receiving consulting and lecture fees from Roche Diagnostics; D.A., M.Sc., S.G. and M.H. report being employees of Roche Diagnostics; D.A., M.Sc. and M.H. report holding stock in Roche; M.Sc. and M.H. report holding a pending patent related to the sFtl-1:PlGF or endoglin:PlGF ratio to rule out onset of pre-eclampsia in pregnant women within a certain time period (PCT/EP2013/063115); M.H. reports holding pending patents related to the dynamics of sFlt-1 or endoglin:PlGF ratio as an indicator for imminent pre-eclampsia or the HELLP syndrome or both (PCT/EP2012/072157) and the prediction of postpartum HELLP syndrome, postpartum eclampsia, or postpartum pre-eclampsia (PCT/EP2015/051457); and S.V. reports receiving consulting fees from Roche Diagnostics, Thermo Fisher, Ferring, and Novartis, and lecture fees from Roche Diagnostics and Thermo Fisher. No other potential conflict of interest relevant to this article was reported.
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