Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Journal of Perinatal Medicine

Official Journal of the World Association of Perinatal Medicine

Editor-in-Chief: Dudenhausen, Joachim W.

Editorial Board Member: / Bancalari, Eduardo / Milner, Anne / Genc, Mehmet R. / Chervenak, Frank A. / Chappelle, Joseph / Bergmann, Renate L. / Bernardes, J.F. / Bevilacqua, G. / Blickstein, Isaac / Cabero Roura, Luis / Carbonell-Estrany, Xavier / Carrera, Jose M. / D`Addario, Vincenzo / D'Alton, MD, Mary E. / Dimitrou, G. / Grunebaum, Amos / Hentschel, Roland / Köpcke, W. / Kawabata, Ichiro / Keirse, Marc J.N.C. / Kurjak M.D., Asim / Lee, Ben H. / Levene, Malcolm / Lockwood, Charles J. / Marsal, Karel / Makatsariya, Alexander / Nishida, Hiroshi / Papp, Zoltán / Pejaver, Ranjan Kumar / Pooh, Ritsuko K. / Romero, Roberto / Saugstad, Ola D. / Schenker, Joseph G. / Sen, Cihat / Seri, Istvan / Vetter, Klaus / Winn, Hung N. / Young, Bruce K. / Zimmermann, Roland

9 Issues per year

IMPACT FACTOR 2016: 1.577
5-year IMPACT FACTOR: 1.705

CiteScore 2016: 1.49

SCImago Journal Rank (SJR) 2016: 0.602
Source Normalized Impact per Paper (SNIP) 2016: 0.832

See all formats and pricing
More options …
Volume 42, Issue 1 (Jan 2014)


The importance of repeated measurements of the sFlt-1/PlGF ratio for the prediction of preeclampsia and intrauterine growth restriction

Katharina Schoofs
  • Department of Obstetrics, Charité University Medicine, Berlin, Germany
/ Ulrike Grittner
  • Department for Biostatistics and Clinical Epidemiology, Charité University Medicine, Berlin, Germany
/ Theresa Engels
  • Department of Obstetrics, Charité University Medicine, Berlin, Germany
/ Juliane Pape
  • Department of Gynecology and Obstetrics, DRK Berlin Westend, Berlin, Germany
/ Barbara Denk
  • Roche Professional Diagnostics, Penzberg, Germany
/ Wolfgang Henrich
  • Department of Obstetrics, Charité University Medicine, Berlin, Germany
/ Stefan Verlohren
  • Corresponding author
  • Department of Obstetrics, Charité University Medicine, Berlin, Germany
  • Email:
Published Online: 2013-08-09 | DOI: https://doi.org/10.1515/jpm-2013-0074


Aims: The sFlt-1/PlGF ratio has been evaluated as a diagnostic marker for preeclampsia (PE). The aim of this study was to explore the use of the sFlt-1/PlGF ratio as an aid in prediction for PE.

Methods: 150 patients with a high risk for PE were enrolled in this prospective study. Groups were compared according to the pregnancy outcome: controls (n=114), intrauterine growth restriction (IUGR) (n=14) and PE (n=22) with subclassification early PE<34 weeks (n=6). Measurements of sFlt-1 and PlGF were performed on the automated Elecsys system. Statistical comparison of the sFlt-1/PlGF ratio in different outcome groups and a mixed model analysis using random intercept models were performed.

Results: The sFlt-1/PlGF ratio was significantly higher in pregnancies complicated by PE up to 4 weeks before clinical diagnosis compared to controls (106.7±47.7 vs. 21.0±4.1; P=0.02). Levels of the sFlt-1/PlGF ratio were higher throughout pregnancy in women with IUGR compared to PE/control patients (intercept 1.57 vs. 1.30/0.67; P<0.05). The slope for the sFlt-1/PlGF ratio was significantly higher in PE and IUGR pregnancies compared to controls, indicating that a steep increase of the sFlt-1/PlGF ratio correlates with pathologic pregnancy outcomes.

Conclusion: The sFlt-1/PlGF ratio can identify pathologic pregnancy outcomes such as IUGR and PE before clinical diagnosis. Repeated measurements are necessary to assess the dynamics in serum values. The time-dependent slope of the sFlt-1/PlGF ratio is predictive for future pregnancy outcome and risk of developing preeclampsia.

Keywords: Angiogenic factors; biomarker; hypertension; IUGR; placental dysfunction; PlGF; prediction; preeclampsia; pregnancy; sFlt-1


  • [1]

    Burton GJ, Yung HW, Cindrova-Davies T, Charnock-Jones DS. Placental endoplasmic reticulum stress and oxidative stress in the pathophysiology of unexplained intrauterine growth restriction and early onset preeclampsia. Placenta. 2009;30 Suppl A:S43–8.CrossrefWeb of ScienceGoogle Scholar

  • [2]

    Duley L. The global impact of pre-eclampsia and eclampsia. Semin Perinatol. 2009;33:130–7.Google Scholar

  • [3]

    Erez O, Romero R, Espinoza J, Fu W, Todem D, Kusanovic JP, et al. The change in concentrations of angiogenic and anti-angiogenic factors in maternal plasma between the first and second trimesters in risk assessment for the subsequent development of preeclampsia and small-for-gestational age. J Matern Fetal Neonatal Med. 2008;21:279–87.Web of ScienceGoogle Scholar

  • [4]

    Iacovella C, Franchi M, Egbor M, Bhide A, Thilaganathan B. Relationship of first-trimester uterine artery Doppler to late stillbirth. Prenat Diagn. 2012;32:557–61.Web of ScienceGoogle Scholar

  • [5]

    Kaufmann P, Black S, Huppertz B. Endovascular trophoblast invasion: implications for the pathogenesis of intrauterine growth retardation and preeclampsia. Biol Reprod. 2003;69:1–7.Google Scholar

  • [6]

    Khan KS, Wojdyla D, Say L, Gülmezoglu AM, Van Look PFA. WHO analysis of causes of maternal death: a systematic review. Lancet. 2006;367:1066–74.Google Scholar

  • [7]

    Lam C, Lim KH, Karumanchi SA. Circulating angiogenic factors in the pathogenesis and prediction of preeclampsia. Hypertension. 2005;46:1077–85.Google Scholar

  • [8]

    Lapaire O, Shennan A, Stepan H. The preeclampsia biomarkers soluble fms-like tyrosine kinase-1 and placental growth factor: current knowledge, clinical implications and future application. Eur J Obstet Gynecol Reprod Biol. 2010;151:122–9.Web of ScienceGoogle Scholar

  • [9]

    Levine RJ, Lam C, Qian C, Yu KF, Maynard SE, Sachs BP, et al. Soluble endoglin and other circulating antiangiogenic factors in preeclampsia. N Engl J Med. 2006;355:992–1005.Google Scholar

  • [10]

    Levine RJ, Maynard SE, Qian C, Lim KH, England LJ, Yu KF, et al. Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med. 2004;350:672–83.Google Scholar

  • [11]

    Maynard SE, Crawford SL, Bathgate S, Yan J, Robidoux L, Moore M, et al. Gestational angiogenic biomarker patterns in high risk preeclampsia groups. Am J Obstet Gynecol. 2013 Mar 18. doi:pii: S0002-9378(13)00290-1. 10.1016/j.ajog.2013.03.017. [Epub ahead of print].CrossrefGoogle Scholar

  • [12]

    Maynard SE, Min JY, Merchan J, Lim KH, Li J, Mondal S, et al. Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest. 2003;111:649–58.Google Scholar

  • [13]

    Moghbeli N, Srinivas SK, Bastek J, Lu Y, Putt ME, Cappola TP, et al. N-terminal pro-brain natriuretic Peptide as a biomarker for hypertensive disorders of pregnancy. Am J Perinatol. 2010;27:313–9.Web of ScienceGoogle Scholar

  • [14]

    Moore Simas TA, Crawford SL, Solitro MJ, Frost SC, Meyer BA, Maynard SE. Angiogenic factors for the prediction of preeclampsia in high-risk women. Am J Obstet Gynecol. 2007;197:244.e1–8.Google Scholar

  • [15]

    Ohkuchi A, Hirashima C, Suzuki H, Takahashi K, Yoshida M, Matsubara S, et al. Evaluation of a new and automated electrochemiluminescence immunoassay for plasma sFlt-1 and PlGF levels in women with preeclampsia. Hypertens Res. 2010;33:422–7.Web of ScienceGoogle Scholar

  • [16]

    Pilliod RA, Cheng YW, Snowden JM, Doss AE, Caughey AB. The risk of intrauterine fetal death in the small-for-gestational-age fetus. Am J Obstet Gynecol. 2012;207:318.e1–6.Google Scholar

  • [17]

    Poon LC, Syngelaki A, Akolekar R, Lai J, Nicolaides KH. Combined Screening for Preeclampsia and Small for Gestational Age at 11–13 Weeks. Fetal Diagn Ther. 2013;33(1):16-27. doi: 10.1159/000341712. Epub 2012 Sep 13.CrossrefWeb of ScienceGoogle Scholar

  • [18]

    Rana S, Karumanchi SA, Levine RJ, Venkatesha S, Rauh-Hain JA, Tamez H, et al. Sequential changes in antiangiogenic factors in early pregnancy and risk of developing preeclampsia. Hypertension. 2007;50:137–42.Web of ScienceGoogle Scholar

  • [19]

    Rana S, Powe CE, Salahuddin S, Verlohren S, Perschel FH, Levine RJ, et al. Angiogenic factors and the risk of adverse outcomes in women with suspected preeclampsia. Circulation. 2012;125:911–9.Web of ScienceGoogle Scholar

  • [20]

    Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. Am J Obstet Gynecol. 2000;183:S1–S22.Google Scholar

  • [21]

    Schlembach D, Wallner W, Sengenberger R, Stiegler E, Mörtl M, Beckmann MW, et al. Angiogenic growth factor levels in maternal and fetal blood: correlation with Doppler ultrasound parameters in pregnancies complicated by pre-eclampsia and intrauterine growth restriction. Ultrasound Obstet Gynecol. 2007;29:407–13.Google Scholar

  • [22]

    Shibata E, Rajakumar A, Powers RW, Larkin RW, Gilmour C, Bodnar LM, et al. Soluble fms-like tyrosine kinase 1 is increased in preeclampsia but not in normotensive pregnancies with small-for-gestational-age neonates: relationship to circulating placental growth factor. J Clin Endocrinol Metab. 2005;90:4895–903.Google Scholar

  • [23]

    Stepan H, Jank A. Angiogene Faktoren und ihre Rolle in der Entstehung und Vorhersage der Präeklampsie. Z Geburtshilfe Neonatol. 2009;213:101,5.Google Scholar

  • [24]

    Stepan H, Unversucht A, Wessel N, Faber R. Predictive value of maternal angiogenic factors in second trimester pregnancies with abnormal uterine perfusion. Hypertension. 2007;49:818–24.Web of ScienceGoogle Scholar

  • [25]

    Thadhani R, Kisner T, Hagmann H, Bossung V, Noack S, Schaarschmidt W, et al. Pilot study of extracorporeal removal of soluble fms-like tyrosine kinase 1 in preeclampsia. Circulation. 2011;124:940–50.Web of ScienceGoogle Scholar

  • [26]

    Vandenberghe G, Mensink I, Twisk JW, Blankenstein MA, Heijboer AC, van Vugt JM. First trimester screening for intra-uterine growth restriction and early-onset pre-eclampsia. Prenat Diagn. 2011;31:955–61.Google Scholar

  • [27]

    Vatten LJ, Eskild A, Nilsen TI, Jeansson S, Jenum PA, Staff AC. Changes in circulating level of angiogenic factors from the first to second trimester as predictors of preeclampsia. Am J Obstet Gynecol. 2007;196:239.e1–6.Web of ScienceGoogle Scholar

  • [28]

    Verbeke G, Molenberghs G. Linear mixed models for longitudinal data. New York: Springer; 2008. p. 592.Google Scholar

  • [29]

    Verlohren S, Galindo A, Schlembach D, Zeisler H, Herraiz I, Moertl MG, et al. An automated method for the determination of the sFlt-1/PIGF ratio in the assessment of preeclampsia. Am J Obstet Gynecol. 2010;202:161.e1–e11.Web of ScienceGoogle Scholar

  • [30]

    Verlohren S, Herraiz I, Lapaire O, Schlembach D, Moertl M, Zeisler H, 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.e1–8.Web of ScienceGoogle Scholar

  • [31]

    Zhang J, Klebanoff MA, Roberts JM. Prediction of adverse outcomes by common definitions of hypertension in pregnancy. Obstet Gynecol. 2001;97:261–7.Google Scholar

About the article

Corresponding author: Stefan Verlohren, Department of Obstetrics, Charité University Medicine, Berlin, Germany, E-mail:

Received: 2013-04-05

Accepted: 2013-07-08

Published Online: 2013-08-09

Published in Print: 2014-01-01

Citation Information: Journal of Perinatal Medicine, ISSN (Online) 1619-3997, ISSN (Print) 0300-5577, DOI: https://doi.org/10.1515/jpm-2013-0074.

Export Citation

©2014 by Walter de Gruyter Berlin Boston. Copyright Clearance Center

Comments (0)

Please log in or register to comment.
Log in