CC BY-NC-ND 4.0 · Geburtshilfe Frauenheilkd 2025; 85(02): 190-199
DOI: 10.1055/a-2497-8104
GebFra Science
Original Article

Risk for Imminent Delivery in Preeclampsia Based on the sFlt-1/PlGF Ratio: Do We Need New Cut-Offs?

Risiko für eine drohende Entbindung bei Präeklampsie basierend auf dem sFlt-1/PlGF-Quotienten: Brauchen wir neue Grenzwerte?
Sabine Enengl 
1   Department of Gynecology, Obstetrics and Gynecological Endocrinology, Kepler University Hospital, Johannes Kepler University Linz, Linz, Austria (Ringgold ID: RIN27266)
,
Peter Oppelt
1   Department of Gynecology, Obstetrics and Gynecological Endocrinology, Kepler University Hospital, Johannes Kepler University Linz, Linz, Austria (Ringgold ID: RIN27266)
,
Patrick Stelzl
1   Department of Gynecology, Obstetrics and Gynecological Endocrinology, Kepler University Hospital, Johannes Kepler University Linz, Linz, Austria (Ringgold ID: RIN27266)
,
Iris Scharnreitner
1   Department of Gynecology, Obstetrics and Gynecological Endocrinology, Kepler University Hospital, Johannes Kepler University Linz, Linz, Austria (Ringgold ID: RIN27266)
,
Reinhard Altmann
1   Department of Gynecology, Obstetrics and Gynecological Endocrinology, Kepler University Hospital, Johannes Kepler University Linz, Linz, Austria (Ringgold ID: RIN27266)
,
Julia Grienberger
1   Department of Gynecology, Obstetrics and Gynecological Endocrinology, Kepler University Hospital, Johannes Kepler University Linz, Linz, Austria (Ringgold ID: RIN27266)
,
Philipp Hermann
2   Statistical Consulting and Data Analysis, Center for Clinical Research, Faculty of Medicine, Johannes Kepler University Linz, Linz, Austria (Ringgold ID: RIN27266)
,
Helga Wagner
2   Statistical Consulting and Data Analysis, Center for Clinical Research, Faculty of Medicine, Johannes Kepler University Linz, Linz, Austria (Ringgold ID: RIN27266)
3   Institute of Applied Statistics, Medical Statistics and Biometry, Johannes Kepler University Linz, Linz, Austria
,
Marlene Rezk-Füreder
4   Experimental Gynecology, Obstetrics and Gynecological Endocrinology, Kepler University Hospital Linz, Johannes Kepler University Linz, Linz, Austria
,
Ilinca Damian
5   Department of Cardiac, Vascular and Thoracic Surgery, Kepler University Hospital, Johannes Kepler University Linz, Linz, Austria (Ringgold ID: RIN27266)
,
Lena Maghörndl
1   Department of Gynecology, Obstetrics and Gynecological Endocrinology, Kepler University Hospital, Johannes Kepler University Linz, Linz, Austria (Ringgold ID: RIN27266)
› Author Affiliations
› Further Information
  Permissions and Reprints

Abstract

Introduction

It is still difficult to predict the outcome of preeclampsia and determine the individual procedure with regards to the time of birth. Cut-offs of the sFlt-1/PlGF ratio with a high risk for imminent delivery have been previously published and analyzed by our study group, but could not be confirmed. The aim of the current study is to re-evaluate the described cut-off values again in a new period of time.

Materials and Methods

We performed a retrospective analysis (IRB 1279/2020) including all preeclampsia patients delivering in our department over a 3-year period. Patients were divided into 2 groups – gestational week 24+0–33+6 with an s-Flt1/PlGF > 655.2 and 34+0–37+0 weeks with an sFlt-1/PlGF > 201 and were compared with preeclampsia patients of the same weeks with sFlt-1/PlGF values below the described cut-offs. Correlation between sFlt-1/PlGF ratio and time to delivery was assessed.

Results

The association between sFlt-1/PlGF above the threshold and delivery within 48 h is significant for the high ratio early group (p < 0.01) but not for the high ratio late group (p = 0.62). In the early group, 60% of patients with sFlt-1/PlGF > 655.2 but only 8% in the low ratio group delivered within 48 h. In both the early and the late preeclampsia group, a high number of patients remained pregnant even though they showed elevated ratios.

Conclusion

High sFlt-1/PlGF ratios seem to correlate with a shorter pregnancy duration to some extent. Nevertheless, not all patients need to be delivered within 48 h, so the decision should never be based on the laboratory test alone.

Zusammenfassung

Einleitung

Es ist immer noch schwierig, das Outcome bei Präeklampsie vorherzusagen und das individuelle Vorgehen hinsichtlich des richtigen Zeitpunkts der Entbindung festzulegen. Unsere Arbeitsgruppe hat zwar Schwellenwerte für den sFlt-1/PlGF-Quotienten, die mit einem höheren Risiko für eine bevorstehende Entbindung verbunden sind, veröffentlicht und analysiert, aber die Werte konnten bisher nicht bestätigt werden. Ziel dieser aktuellen Studie war es, eine Neubewertung der beschriebenen Schwellenwerte für einen neuen Zeitabschnitt vorzunehmen.

Material und Methoden

Es wurde eine retrospektive Analyse (IRB 1279/2020) der Patientinnen vorgenommen, die innerhalb von 3 Jahren in unserer Abteilung entbunden haben, einschließlich aller Patientinnen mit Präeklampsie. Die Patientinnen wurden in 2 Gruppen eingeteilt: Schwangerschaftswoche 24+0–33+6 mit einem s-Flt1/PlGF > 655,2 und Schwangerschaftswoche 34+0–37+0 mit einem sFlt-1/PlGF > 201. Die Gruppen wurden mit Patientinnen mit Präeklampsie in derselben Schwangerschaftswoche und mit demselben sFlt-1/PlGF-Quotienten unterhalb der oben beschriebenen Schwellenwerte verglichen. Die Korrelation zwischen dem sFlt-1/PlGF-Quotienten und der Zeit bis zur Entbindung wurde bewertet.

Ergebnisse

Die Beziehung zwischen sFlt-1/PlGF-Quotienten oberhalb des Schwellenwerts und einer Entbindung innerhalb von 48 Stunden war signifikant für die früh entbundene Gruppe mit einem hohen Quotienten (p < 0,01), nicht aber für die spät entbundene Gruppe mit einem hohen Quotienten (p = 0,62). In der Gruppe der früh Entbundenen haben 60% der Patientinnen mit einem sFlt-1/PlGF > 655,2, aber nur 8% mit einem niedrigen Quotienten innerhalb von 48 Stunden entbunden. Sowohl in der frühen als auch in der späten Präeklampsiegruppe blieben eine hohe Anzahl der Patientinnen schwanger, obwohl sie erhöhte Quotienten aufwiesen.

Schlussfolgerung

Höhere sFlt-1/PlGF-Quotienten scheinen bis zu einem gewissen Grad mit einer kürzeren Schwangerschaftsdauer zu korrelieren. Trotzdem müssen nicht alle Patientinnen innerhalb von 48 Stunden entbunden werden, und die Entscheidung sollte nie auf den Ergebnissen der Laboruntersuchung alleine beruhen.

Keywords

preeclampsia - sFlt-1/PlGF - soluble fms-like tyrosine kinase-1 - placental growth factor - time to delivery

Schlüsselwörter

Präeklampsie - sFlt-1/PlGF - lösliche Fms-like tyrosine kinase-1 - Plazenta-Wachstumsfaktor - Zeit zur Entbindung


Publication History

Received: 28 August 2024

Accepted after revision: 04 December 2024

Article published online:
06 February 2025

© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

 

  • References

  • 1 Lo JO, Mission JF, Caughey AB. Hypertensive disease of pregnancy and maternal mortality. Curr Opin Obstet Gynecol 2013; 25: 124-132
    CrossrefPubMedSearch in Google Scholar
  • 2 Hutcheon JA, Lisonkova S, Joseph KS. Epidemiology of pre-eclampsia and the other hypertensive disorders of pregnancy. Best Pract Res Clin Obstet Gynaecol 2011; 25: 391-403
    CrossrefPubMedSearch in Google Scholar
  • 3 World Health Organization. WHO Recommendations for Prevention and Treatment of Pre-Eclampsia and Eclampsia. 2011 Accessed November 30, 2022 at: http://iris.wpro.who.int/handle/10665.1/13983
    Search in Google Scholar
  • 4 Harrison MS, Goldenberg RL. Global burden of prematurity. Semin Fetal Neonatal Med 2016; 21: 74-79
    CrossrefPubMedSearch in Google Scholar
  • 5 Goldenberg RL, Culhane JF, Iams JD. et al. Preterm Birth 1 Epidemiology and causes of preterm birth. Lancet 2008; 371: 10
    CrossrefPubMedSearch in Google Scholar
  • 6 Roberts JM, Pearson G, Cutler J. et al. Summary of the NHLBI Working Group on Research on Hypertension During Pregnancy. Hypertension 2003; 41: 437-445
    CrossrefPubMedSearch in Google Scholar
  • 7 Duley L. The Global Impact of Pre-eclampsia and Eclampsia. Semin Perinatol 2009; 33: 130-137
    CrossrefPubMedSearch in Google Scholar
  • 8 Tranquilli AL, Dekker G, Magee L. et al. The classification, diagnosis and management of the hypertensive disorders of pregnancy: A revised statement from the ISSHP. Pregnancy Hypertens 2014; 4: 97-104
    CrossrefPubMedSearch in Google Scholar
  • 9 Magee LA, Pels A, Helewa M. et al. Diagnosis, Evaluation, and Management of the Hypertensive Disorders of Pregnancy: Executive Summary. J Obstet Gynaecol Can 2014; 36: 416-438
    CrossrefPubMedSearch in Google Scholar
  • 10 Burton GJ, Redman CW, Roberts JM. et al. Pre-eclampsia: pathophysiology and clinical implications. BMJ 2019; 366: l2381
    CrossrefPubMedSearch in Google Scholar
  • 11 Maynard SE, Karumanchi SA. Angiogenic Factors and Preeclampsia. Semin Nephrol 2011; 31: 33-46
    CrossrefPubMedSearch in Google Scholar
  • 12 Levine RJ, Yu KF, Sibai BM. et al. Soluble Endoglin and Other Circulating Antiangiogenic Factors in Preeclampsia. N Engl J Med 2006; 355: 992-1005
    CrossrefPubMedSearch in Google Scholar
  • 13 Rana S, Lemoine E, Granger JP. et al. Compendium on the Pathophysiology and Treatment of Hypertension, Preeclampsia – Pathophysiology, Challenges, and Perspectives. Circ Res 2019; 124: 1094-1112
    CrossrefPubMedSearch in Google Scholar
  • 14 Zeisler H, Llurba E, Chantraine F. et al. Predictive Value of the sFlt-1:PlGF Ratio in Women with Suspected Preeclampsia. N Engl J Med 2016; 374: 13-22
    CrossrefPubMedSearch in Google Scholar
  • 15 Verlohren S, Herraiz I, Lapaire O. et al. New Gestational Phase–Specific Cutoff Values for the Use of the Soluble fms-Like Tyrosine Kinase-1/Placental Growth Factor Ratio as a Diagnostic Test for Preeclampsia. Hypertension 2014; 63: 346-352
    CrossrefPubMedSearch in Google Scholar
  • 16 Cerdeira AS, O’Sullivan J, Ohuma EO. et al. Performance of soluble fms-like tyrosine kinase-1–to–placental growth factor ratio of ≥ 85 for ruling in preeclampsia within 4 weeks. Am J Obstet Gynecol 2021; 224: 322-323
    CrossrefPubMedSearch in Google Scholar
  • 17 Ukah UV, Hutcheon JA, Payne B. et al. Placental Growth Factor as a Prognostic Tool in Women With Hypertensive Disorders of Pregnancy: A Systematic Review. Hypertension 2017; 70: 1228-1237
    CrossrefPubMedSearch in Google Scholar
  • 18 Zeisler H, Llurba E, Chantraine F. et al. Soluble fms-Like Tyrosine Kinase-1-to-Placental Growth Factor Ratio and Time to Delivery in Women With Suspected Preeclampsia. Obstet Gynecol 2016; 128: 261-269
    CrossrefPubMedSearch in Google Scholar
  • 19 Verlohren S, Herraiz I, Lapaire O. et al. The sFlt-1/PlGF ratio in different types of hypertensive pregnancy disorders and its prognostic potential in preeclamptic patients. Am J Obstet Gynecol 2012; 206: 58.e1-58.e8
    CrossrefPubMedSearch in Google Scholar
  • 20 Enengl S, Mayer RB, Le Renard PE. et al. Retrospective evaluation of established cut-off values for the sFlt-1/PlGF ratio for predicting imminent delivery in preeclampsia patients. Pregnancy Hypertens 2020; 19: 143-149
    CrossrefPubMedSearch in Google Scholar
  • 21 Stepan H, Kuse-Föhl S, Klockenbusch W. et al. Diagnosis and Treatment of Hypertensive Pregnancy Disorders. Guideline of DGGG (S1-Level, AWMF Registry No. 015/018, December 2013). Geburtshilfe Frauenheilkd 2015; 75: 900-914
    Thieme ConnectPubMedSearch in Google Scholar
  • 22 ACOG Committee Opinion No. 764: Medically Indicated Late-Preterm and Early-Term Deliveries. Obstet Gynecol [Anonym]. 2019; 133: e151-e155
    CrossrefPubMedSearch in Google Scholar
  • 23 National Institute for Health and Care Excellence (NICE). Hypertension in Pregnancy: Diagnosis and Management. National Institute for Health and Care Excellence (NICE). 2019 Accessed November 30, 2022 at: http://www.ncbi.nlm.nih.gov/books/NBK546004/
    Search in Google Scholar
  • 24 Brodowski L, Knoth M, Zehner L. et al. Assessing Severity and Need for Delivery in Early Onset Preeclampsia Before 32 Weeks of Gestation: a Delphi Consensus Procedure. Geburtshilfe Frauenheilkd 2024; 84: 760-772
    Thieme ConnectPubMedSearch in Google Scholar
  • 25 Chaiworapongsa T, Romero R, Savasan ZA. et al. Maternal plasma concentrations of angiogenic/anti-angiogenic factors are of prognostic value in patients presenting to the obstetrical triage area with the suspicion of preeclampsia. J Matern Fetal Neonatal Med 2011; 24: 1187-1207
    CrossrefPubMedSearch in Google Scholar
  • 26 Chaiworapongsa T, Romero R, Korzeniewski SJ. et al. Plasma concentrations of angiogenic/anti-angiogenic factors have prognostic value in women presenting with suspected preeclampsia to the obstetrical triage area: a prospective study. J Matern Fetal Neonatal Med 2014; 27: 132-144
    CrossrefPubMedSearch in Google Scholar
  • 27 Álvarez-Fernández I, Prieto B, Rodríguez V. et al. New biomarkers in diagnosis of early onset preeclampsia and imminent delivery prognosis. Clin Chem Lab Med 2014; 52: 1159-1168
    CrossrefPubMedSearch in Google Scholar
  • 28 Saleh L, Vergouwe Y, Van Den Meiracker AH. et al. Angiogenic Markers Predict Pregnancy Complications and Prolongation in Preeclampsia: Continuous Versus Cutoff Values. Hypertension 2017; 70: 1025-1033
    CrossrefPubMedSearch in Google Scholar
  • 29 Perry H, Binder J, Kalafat E. et al. Angiogenic Marker Prognostic Models in Pregnant Women With Hypertension. Hypertension 2020; 75: 755-761
    CrossrefPubMedSearch in Google Scholar
  • 30 Gaccioli F, Sovio U, Cook E. et al. Screening for fetal growth restriction using ultrasound and the sFLT1/PlGF ratio in nulliparous women: a prospective cohort study. Lancet Child Adolesc Health 2018; 2: 569-581
    CrossrefPubMedSearch in Google Scholar
  • 31 Villalaín C, Herraiz I, Valle L. et al. Maternal and Perinatal Outcomes Associated With Extremely High Values for the sFlt-1 (Soluble fms-Like Tyrosine Kinase 1)/PlGF (Placental Growth Factor) Ratio. J Am Heart Assoc 2020; 9: e015548
    CrossrefPubMedSearch in Google Scholar
  • 32 Chappell LC, Brocklehurst P, Green ME. et al. Planned early delivery or expectant management for late preterm pre-eclampsia (PHOENIX): a randomised controlled trial. Lancet 2019; 394: 1181-1190
    CrossrefPubMedSearch in Google Scholar
  • 33 Peguero A, Herraiz I, Perales A. et al. Placental growth factor testing in the management of late preterm preeclampsia without severe features: a multicenter, randomized, controlled trial. Am J Obstet Gynecol 2021; 225: 308.e1-308.e14
    CrossrefPubMedSearch in Google Scholar
  • 34 Rana S, Powe CE, Salahuddin S. et al. Angiogenic Factors and the Risk of Adverse Outcomes in Women With Suspected Preeclampsia. Circulation 2012; 125: 911-919
    CrossrefPubMedSearch in Google Scholar
  • 35 Graupner O, Verlohren S, Groten T. et al. Significance of the sFlt-1/PlGF Ratio in Certain Cohorts – What Needs to be Considered?. Geburtshilfe Frauenheilkd 2024; 84: 629-634
    Thieme ConnectPubMedSearch in Google Scholar
  • 36 Zhang J, Klebanoff MA, Roberts JM. Prediction of Adverse Outcomes by Common Definitions of Hypertension in Pregnancy. Obstet Gynecol 2001; 97: 261-267
    CrossrefPubMedSearch in Google Scholar
  • 37 Dröge LA, Perschel FH, Stütz N. et al. Prediction of Preeclampsia-Related Adverse Outcomes With the sFlt-1 (Soluble fms-Like Tyrosine Kinase 1)/PlGF (Placental Growth Factor)-Ratio in the Clinical Routine: A Real-World Study. Hypertension 2021; 77: 461-471
    CrossrefPubMedSearch in Google Scholar