Pilot study: placental biomarker predictive capability (sFlt-1, PlGF and their ratio) of postpartum maternal outcome

  • Amr HamzaEmail author
  • Ch. Gerlinger
  • J. Radosa
  • E. F. Solomayer
  • J. Hagmann
  • U. Sester
  • R. Bohle
  • R. Stroeder
  • Z. Takacs
  • G. Meyberg-Solomayer
  • I. Juhasz-Boess
  • M. Kasoha
Maternal-Fetal Medicine



Prenatal measurement of placental biomarkers was able to improve screening and diagnosis of preeclampsia. Little is known about the clinical role of placental biomarkers in the postpartum period.


This study is a prospective monocentric trial that included a total of 30 women with preeclamptic pregnancies. Serum placental biomarkers including soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF) were measured before and 2 h after delivery by Enzyme-Linked Immunosorbent Assay (ELISA) using commercially available kits according to manufacturer’s instructions and correlated with the postpartum outcome.


Postpartum higher serum PlGF level was associated with postpartum elevation of the systolic blood pressure. Yet, the placental biomarkers were not able to predict general worsening of postpartum preeclampsia or other individual clinical or laboratory parameters.


Serum concentrations of sFlt-1 and PlGF or their ratio in our study cohort did not completely predict the occurrence of postpartum preeclampsia. Yet, postpartum higher serum PlGF level was associated with postpartum elevation of the systolic blood pressure.


Postpartum preeclampsia Placental biomarkers PlGF sFlt-1 



The authors would like to thank the Department of Obstetrics and Gynecology for providing the authors with the necessary logistical and financial support.

Author contributions

AH: Conceptualization, methodology and project administration, validation of data and writing of the manuscript; CG: Statistical analysis; JCR: Formal analysis, reviewing and editing; EFS: Funding and supervising the project, reviewing and editing; JH: Recruitment, laboratory analysis; US: Conceptualization, Reviewing and editing; RB: Conceptualization, Reviewing and editing; RS: Data curation, reviewing and editing; ZT: Data curation, reviewing and editing; IJ: Reviewing and editing; RS: Reviewing and editing; GM: Reviewing and editing the manuscript; MK: Conceptualization, formal analysis, methodology, reviewing and editing the manuscript.


The study and manuscript were funded by the Department of Obstetrics and Gynecology, University of Saarland.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Hirashima C, Ohkuchi A, Arai F et al (2005) Establishing reference values for both total soluble Fms-like tyrosine kinase 1 and free placental growth factor in pregnant women. Hypertens Res Off J Jpn Soc Hypertens 28(9):727–732CrossRefGoogle Scholar
  2. 2.
    Barleon B, Sozzani S, Zhou D, Weich HA, Mantovani A, Marme D (1996) Migration of human monocytes in response to vascular endothelial growth factor (VEGF) is mediated via the VEGF receptor flt-1. Blood 87(8):3336–3343Google Scholar
  3. 3.
    Chaiworapongsa T, Romero R, Espinoza J et al (2004) Evidence supporting a role for blockade of the vascular endothelial growth factor system in the pathophysiology of preeclampsia: Young Investigator Award. Am J Obstetr Gynecol 190(6):1541–1547 (discussion 7–50) CrossRefGoogle Scholar
  4. 4.
    Levine RJ, Maynard SE, Qian C et al (2004) Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med 350(7):672–683CrossRefGoogle Scholar
  5. 5.
    Salahuddin S, Lee Y, Vadnais M, Sachs BP, Karumanchi SA, Lim KH (2007) Diagnostic utility of soluble fms-like tyrosine kinase 1 and soluble endoglin in hypertensive diseases of pregnancy. Am J Obstet Gynecol 197(1):28.e1–28.e6CrossRefGoogle Scholar
  6. 6.
    Maglione D, Guerriero V, Viglietto G, Delli-Bovi P, Persico MG (1991) Isolation of a human placenta cDNA coding for a protein related to the vascular permeability factor. Proc Natl Acad Sci USA 88(20):9267–9271CrossRefGoogle Scholar
  7. 7.
    Verlohren S, Herraiz I, Lapaire O et al (2012) The sFlt-1/PlGF ratio in different types of hypertensive pregnancy disorders and its prognostic potential in preeclamptic patients. Am J Obstet Gynecol 206(1):58.e1–58.e8CrossRefGoogle Scholar
  8. 8.
    Herraiz I, Llurba E, Verlohren S, Galindo A (2018) Update on the diagnosis and prognosis of preeclampsia with the Aid of the sFlt-1/PlGF ratio in singleton pregnancies. Fetal Diagn Ther 43(2):81–89CrossRefGoogle Scholar
  9. 9.
    Stepan H, Hund M, Gencay M et al (2016) A comparison of the diagnostic utility of the sFlt-1/PlGF ratio versus PlGF alone for the detection of preeclampsia/HELLP syndrome. Hypertens Pregnancy 35(3):295–305CrossRefGoogle Scholar
  10. 10.
    Zeisler H, Llurba E, Chantraine F et al (2016) Predictive value of the sFlt-1:PlGF ratio in women with suspected preeclampsia. N Engl J Med 374(1):13–22CrossRefGoogle Scholar
  11. 11.
    Zeisler H, Llurba E, Chantraine F et al (2016) Soluble fms-like tyrosine kinase-1-to-placental growth factor ratio and time to delivery in women with suspected preeclampsia. Obstet Gynecol 128(2):261–269CrossRefGoogle Scholar
  12. 12.
    Zeisler H, Hund M, Verlohren S (2016) The sFlt-1:PlGF ratio in women with suspected preeclampsia. N Engl J Med 374(18):1785–1786CrossRefGoogle Scholar
  13. 13.
    Droge L, Herraiz I, Zeisler H et al (2015) Maternal serum sFlt-1/PlGF ratio in twin pregnancies with and without pre-eclampsia in comparison with singleton pregnancies. Ultrasound Obstetr Gynecol 45(3):286–293CrossRefGoogle Scholar
  14. 14.
    Stepan H, Herraiz I, Schlembach D et al (2015) Implementation of the sFlt-1/PlGF ratio for prediction and diagnosis of pre-eclampsia in singleton pregnancy: implications for clinical practice. Ultrasound Obstetr Gynecol 45(3):241–246CrossRefGoogle Scholar
  15. 15.
    Herraiz I, Droge LA, Gomez-Montes E, Henrich W, Galindo A, Verlohren S (2014) Characterization of the soluble fms-like tyrosine kinase-1 to placental growth factor ratio in pregnancies complicated by fetal growth restriction. Obstet Gynecol 124(2 Pt 1):265–273CrossRefGoogle Scholar
  16. 16.
    Verlohren S, Herraiz I, Lapaire O et al (2014) 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 (Dallas, Tex: 1979) 63(2):346–352CrossRefGoogle Scholar
  17. 17.
    Schoofs K, Grittner U, Engels T et al (2014) The importance of repeated measurements of the sFlt-1/PlGF ratio for the prediction of preeclampsia and intrauterine growth restriction. J Perinat Med 42(1):61–68CrossRefGoogle Scholar
  18. 18.
    Engels T, Pape J, Schoofs K, Henrich W, Verlohren S (2013) Automated measurement of sFlt1, PlGF and sFlt1/PlGF ratio in differential diagnosis of hypertensive pregnancy disorders. Hypertens Pregnancy 32(4):459–473CrossRefGoogle Scholar
  19. 19.
    Verlohren S, Stepan H, Dechend R (2012) Angiogenic growth factors in the diagnosis and prediction of pre-eclampsia. Clin Sci (London, England: 1979) 122(2):43–52CrossRefGoogle Scholar
  20. 20.
    Verlohren S, Herraiz I, Lapaire O et al (2011) L13. The routine measurement of the sFlt1/PlGF ratio allows differential diagnosis of hypertensive pregnancy disorders and has prognostic potential in preeclamptic patients. Pregnancy Hypertens 1(3–4):245–246CrossRefGoogle Scholar
  21. 21.
    Verlohren S, Galindo A, Schlembach D et al (2010) An automated method for the determination of the sFlt-1/PlGF ratio in the assessment of preeclampsia. Am J Obstetr Gynecol 202(2):161CrossRefGoogle Scholar
  22. 22.
    Stepan H, Schaarschmidt W, Jank A, Verlohren S, Kratzsch J (2010) Use of angiogenic factors (sFlt-1/PlGF ratio) to confirm the diagnosis of preeclampsia in clinical routine: first experience. Z Geburtshilfe Neonatol 214(6):234–238CrossRefGoogle Scholar
  23. 23.
    Nicolaides KH (2017) Aspirin versus placebo in pregnancies at high risk for preterm preeclampsia. N Engl J Med 377(24):2400Google Scholar
  24. 24.
    Saleh L, van den Meiracker AH, Geensen R et al (2018) Soluble fms-like tyrosine kinase-1 and placental growth factor kinetics during and after pregnancy in women with suspected or confirmed pre-eclampsia. Ultrasound Obstetr Gynecol 51(6):751–757CrossRefGoogle Scholar
  25. 25.
    Kaleta T, Stock A, Panayotopoulos D et al (2016) Predictors of impaired postpartum renal function in women after preeclampsia: results of a prospective single center study. Dis Mark 2016:7861919Google Scholar
  26. 26.
    Stepan H, Kuse-Fohl S, Klockenbusch W et al (2015) Diagnosis and treatment of hypertensive pregnancy disorders. Guideline of DGGG (S1-Level, AWMF Registry No. 015/018, December 2013). Geburtshilfe Frauenheilkunde 75(9):900–914CrossRefGoogle Scholar
  27. 27.
    Sibai BM (2012) Etiology and management of postpartum hypertension-preeclampsia. Am J Obstet Gynecol 206(6):470–475CrossRefGoogle Scholar
  28. 28.
    Voigt M, Fusch C, Olbertz D et al (2006) Analyse des neugeborenenkollektivs der bundesrepublik deutschland. Geburtshilfe Frauenheilkd 66(10):956–970CrossRefGoogle Scholar
  29. 29.
    Noori M, Donald AE, Angelakopoulou A, Hingorani AD, Williams DJ (2010) Prospective study of placental angiogenic factors and maternal vascular function before and after preeclampsia and gestational hypertension. Circulation 122(5):478–487CrossRefGoogle Scholar
  30. 30.
    Ragab A, Goda H, Raghib M, Barakat R, El-Samanoudy A, Badawy A (2013) Does immediate postpartum curettage of the endometrium accelerate recovery from preeclampsia–eclampsia? A randomized controlled trial. Arch Gynecol Obstet 288(5):1035–1038CrossRefGoogle Scholar
  31. 31.
    Matsuo K, Kooshesh S, Dinc M, Sun CC, Kimura T, Baschat AA (2007) Late postpartum eclampsia: report of two cases managed by uterine curettage and review of the literature. Am J Perinatol 24(4):257–266CrossRefGoogle Scholar
  32. 32.
    Alkan A, Tugrul S, Oral O, Uslu H, Kose D, Catakli FT (2006) Effects of postpartum uterine curettage on maternal well-being in severe preeclamptic patients. Clin Exp Obstet Gynecol 33(1):55–58Google Scholar
  33. 33.
    Magann EF, Bass JD, Chauhan SP, Perry KG Jr, Morrison JC, Martin JN Jr (1994) Accelerated recovery from severe preeclampsia: uterine curettage versus nifedipine. J Soc Gynecol Investig 1(3):210–214CrossRefGoogle Scholar
  34. 34.
    Magann EF, Martin JN Jr, Isaacs JD, Perry KG Jr, Martin RW, Meydrech EF (1993) Immediate postpartum curettage: accelerated recovery from severe preeclampsia. Obstet Gynecol 81(4):502–506Google Scholar
  35. 35.
    Ossada V, Jank A, Stepan H (2016) The impact of uterine curettage postpartum on maternal sFlt-1 concentration. J Perinat Med 44(3):351–354CrossRefGoogle Scholar
  36. 36.
    Mc Lean G, Reyes O, Velarde R (2017) Effects of postpartum uterine curettage in the recovery from preeclampsia/eclampsia. A randomized, controlled trial. Pregnancy Hypertens 10:64–69CrossRefGoogle Scholar
  37. 37.
    Clark DE, Smith SK, He Y et al (1998) A vascular endothelial growth factor antagonist is produced by the human placenta and released into the maternal circulation. Biol Reprod 59(6):1540–1548CrossRefGoogle Scholar
  38. 38.
    Cohen J, Vaiman D, Sibai BM, Haddad B (2015) Blood pressure changes during the first stage of labor and for the prediction of early postpartum preeclampsia: a prospective study. Eur J Obstet Gynecol Reprod Biol 184:103–107CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Amr Hamza
    • 1
    Email author
  • Ch. Gerlinger
    • 1
  • J. Radosa
    • 1
  • E. F. Solomayer
    • 1
  • J. Hagmann
    • 1
  • U. Sester
    • 2
  • R. Bohle
    • 3
  • R. Stroeder
    • 1
  • Z. Takacs
    • 1
  • G. Meyberg-Solomayer
    • 1
  • I. Juhasz-Boess
    • 1
  • M. Kasoha
    • 1
  1. 1.Department of Obstetrics and GynecologySaarland UniversityHomburgGermany
  2. 2.Department of Internal Medicine IVSaarland UniversityHomburgGermany
  3. 3.Department of PathologySaarland UniversityHomburgGermany

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