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, MD, FRCOG, Joachim W.

Editorial Board: / Bancalari, Eduardo / Greenough, 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. / Reiss, Irwin / 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

Online
ISSN
1619-3997
See all formats and pricing
More options …
Volume 42, Issue 1

Issues

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

Katharina Schoofs / Ulrike Grittner
  • Department for Biostatistics and Clinical Epidemiology, Charité University Medicine, Berlin, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Theresa Engels / Juliane Pape / Barbara Denk / Wolfgang Henrich / Stefan Verlohren
Published Online: 2013-08-09 | DOI: https://doi.org/10.1515/jpm-2013-0074

Abstract

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

References

  • [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, Volume 42, Issue 1, Pages 61–68, 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

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

[2]
Janine Hoffmann, Victoria Ossada, Marie Weber, and Holger Stepan
Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health, 2017
[3]
Yu-Shan Chang, Chi-Nien Chen, Suh-Fang Jeng, Yi-Ning Su, Chien-Yi Chen, Hung-Chieh Chou, Po-Nien Tsao, and Wu-Shiun Hsieh
Pediatrics & Neonatology, 2017
[4]
Arrigo Fruscalzo, Julia Frommer, Ambrogio P. Londero, Andrea Henze, Florian J. Schweigert, Jerzy-Roch Nofer, Johannes Steinhard, Walter Klockenbusch, Ralf Schmitz, and Jens Raila
Archives of Gynecology and Obstetrics, 2017, Volume 295, Number 5, Page 1157
[5]
Sebastian Kwiatkowski, Barbara Dołęgowska, Ewa Kwiatkowska, Rafał Rzepka, Andrzej Torbè, Magdalena Bednarek-Jędrzejek, and Eric Asselin
PLOS ONE, 2016, Volume 11, Number 10, Page e0165060
[7]
Hee Jin Park, Soo Hyun Kim, Yong Wook Jung, Sung Shin Shim, Ji Yeon Kim, Yeon Kyung Cho, Antonio Farina, Margherita Zanello, Kyoung Jin Lee, and Dong Hyun Cha
BMC Pregnancy and Childbirth, 2014, Volume 14, Number 1
[8]
Fangfang Zeng, Sui Zhu, Martin Chi-Sang Wong, Zuyao Yang, Jinling Tang, Keshen Li, and Xuefen Su
Scientific Reports, 2016, Volume 6, Number 1
[9]
Rafaela A. Costa, Mara S. Hoshida, Eliane A. Alves, Marcelo Zugaib, and Rossana P. V. Francisco
Hypertension in Pregnancy, 2016, Volume 35, Number 2, Page 139
[10]
Sebastian Kwiatkowski, Ewa Kwiatkowska, Rafał Rzepka, Andrzej Torbe, and Barbara Dolegowska
The Journal of Maternal-Fetal & Neonatal Medicine, 2015, Page 1
[11]
Letícia Lemos Jardim, Danyelle Romana Alves Rios, Luíza Oliveira Perucci, Lirlândia Pires de Sousa, Karina Braga Gomes, and Luci Maria S. Dusse
Clinica Chimica Acta, 2015, Volume 447, Page 34
[12]
D. Kappou, S. Sifakis, A. Konstantinidou, N. Papantoniou, and D. Spandidos
Experimental and Therapeutic Medicine, 2015
[13]
H. Stepan, I. Herraiz, D. Schlembach, S. Verlohren, S. Brennecke, F. Chantraine, E. Klein, O. Lapaire, E. Llurba, A. Ramoni, M. Vatish, D. Wertaschnigg, and A. Galindo
Ultrasound in Obstetrics & Gynecology, 2015, Volume 45, Number 3, Page 241
[14]
Yuxiu Liu, Yang Zhao, Ailing Yu, Bin Zhao, Yufang Gao, and Haitao Niu
Archives of Gynecology and Obstetrics, 2015, Volume 292, Number 3, Page 507
[15]
Yuanyuan Zhang, Yanfen Zou, Wenqi Wang, Qing Zuo, Ziyan Jiang, Ming Sun, Wei De, and Lizhou Sun
Journal of Cellular Biochemistry, 2015, Volume 116, Number 4, Page 542
[16]
Allison Knuth, Lawrence Liu, Halden Nielsen, Daniel Merril, Donald S. Torry, and Juan A. Arroyo
American Journal of Reproductive Immunology, 2015, Volume 73, Number 4, Page 330
[17]
Anjali Acharya, Wunnie Brima, Shivakanth Burugu, and Tanvi Rege
Current Hypertension Reports, 2014, Volume 16, Number 11
[18]
Kedak Baltajian, Jonathan L. Hecht, Julia B. Wenger, Saira Salahuddin, Stefan Verlohren, Frank H. Perschel, Zsuzsanna K. Zsengeller, Ravi Thadhani, S. Ananth Karumanchi, and Sarosh Rana
Hypertension in Pregnancy, 2014, Volume 33, Number 4, Page 427
[19]
Nathan S. Fox, Daniel H. Saltzman, Sandip Oppal, Chad K. Klauser, Simi Gupta, and Andrei Rebarber
American Journal of Obstetrics and Gynecology, 2014, Volume 211, Number 4, Page 422.e1
[20]
P. I. Gómez-Arriaga, I. Herraiz, E. A. López-Jiménez, D. Escribano, B. Denk, and A. Galindo
Ultrasound in Obstetrics & Gynecology, 2014, Volume 43, Number 5, Page 525

Comments (0)

Please log in or register to comment.
Log in