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Placental growth factor concentration in maternal circulation decreases after fetal death: lessons from a case series study

  • Maternal-Fetal Medicine
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

Placental growth factor (PlGF) has been suggested as a possible biomarker for major placenta-related disorders such as preeclampsia and intrauterine growth restriction. However, experimental findings suggest that PlGF concentrations may be influenced by other factors besides the placenta. In the present study, we examined how acute fetal injury affects PlGF concentrations in maternal circulation. We therefore monitored PlGF concentrations in maternal circulation before and after feticide.

Methods

A prospective comparative study was performed. Blood samples were drawn prospectively between January and July 2012, before and after feticide at predetermined time points in relation to the procedure (0, 30, 60, and 120 min). The levels of lactate dehydrogenase (LDH) in the maternal circulation were measured to detect acute tissue damage. PlGF concentrations were measured by standard human ELISA.

Results

Following feticide (60 and 120 min), PlGF concentrations decreased significantly compared to the concentrations before feticide. LDH concentrations did not change before and after feticide.

Conclusions

Our finding, along with the detailed review of the literature described in our work, supports a new concept in which primary fetal distress can affect PlGF concentration in maternal circulation. A large-scale study is required to strengthen our finding.

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Abbreviations

IUGR:

Intrauterine growth retardation

LDH:

Lactate dehydrogenase

PlGF:

Placental growth factor

sFLT-1:

Soluble fms-like tyrosine kinase-1

VEGF:

Vascular endothelial growth factor

References

  1. Huppertz B (2011) Placental pathology in pregnancy complications. Thromb Res 127(Suppl 3):S96–S99

    Article  CAS  PubMed  Google Scholar 

  2. Odibo AO, Patel KR, Spitalnik A, Odibo L, Huettner P (2014) Placental pathology, first-trimester biomarkers and adverse pregnancy outcomes. J Perinatol Off J Calif Perinat Assoc 34(3):186–191

    Article  CAS  Google Scholar 

  3. Vintzileos AM, Ananth CV (2014) First trimester prediction of ischemic placental disease. Semin Perinatol 38(3):159–166

    Article  PubMed  Google Scholar 

  4. Sibiude J, Guibourdenche J, Dionne MD, Le Ray C, Anselem O, Serreau R et al (2012) Placental growth factor for the prediction of adverse outcomes in patients with suspected preeclampsia or intrauterine growth restriction. PLoS One 7(11):e50208

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Ghosh D, Sharkey AM, Charnock-Jones DS, Dhawan L, Dhara S, Smith SK et al (2000) Expression of vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) in conceptus and endometrium during implantation in the rhesus monkey. Mol Hum Reprod 6(10):935–941

    Article  CAS  PubMed  Google Scholar 

  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):9267–9271

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Kumasawa K, Ikawa M, Kidoya H, Hasuwa H, Saito-Fujita T, Morioka Y et al (2011) Pravastatin induces placental growth factor (PGF) and ameliorates preeclampsia in a mouse model. Proc Natl Acad Sci USA 108(4):1451–1455

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Levine RJ, Maynard SE, Qian C, Lim KH, England LJ, Yu KF et al (2004) Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med 350(7):672–683

    Article  CAS  PubMed  Google Scholar 

  9. Maynard SE, Min JY, Merchan J, Lim KH, Li J, Mondal S et al (2003) Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest 111(5):649–658

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Benton SJ, Hu Y, Xie F, Kupfer K, Lee SW, Magee LA et al (2012) Can placental growth factor in maternal circulation identify fetuses with placental intrauterine growth restriction? Am J Obstet Gynecol 206(2):163e1-7

    Google Scholar 

  11. Romero R, Nien JK, Espinoza J, Todem D, Fu W, Chung H et al (2008) A longitudinal study of angiogenic (placental growth factor) and anti-angiogenic (soluble endoglin and soluble vascular endothelial growth factor receptor-1) factors in normal pregnancy and patients destined to develop preeclampsia and deliver a small for gestational age neonate. J Matern Fetal Neonatal Med 21(1):9–23

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Wallner W, Sengenberger R, Strick R, Strissel PL, Meurer B, Beckmann MW et al (2007) Angiogenic growth factors in maternal and fetal serum in pregnancies complicated by intrauterine growth restriction. Clin Sci (Lond) 112(1):51–57

    Article  CAS  Google Scholar 

  13. Signore C, Mills JL, Qian C, Yu K, Lam C, Epstein FH et al (2006) Circulating angiogenic factors and placental abruption. Obstet Gynecol 108(2):338–344

    Article  CAS  PubMed  Google Scholar 

  14. Espinoza J, Romero R, Nien JK, Kusanovic JP, Richani K, Gomez R et al (2006) A role of the anti-angiogenic factor sVEGFR-1 in the ‘mirror syndrome’ (Ballantyne’s syndrome). J Matern Fetal Neonatal Med 19(10):607–613

    Article  CAS  PubMed  Google Scholar 

  15. Stepan H, Faber R (2006) Elevated sFlt1 level and preeclampsia with parvovirus-induced hydrops. N Engl J Med 354(17):1857–1858

    Article  CAS  PubMed  Google Scholar 

  16. Kusanovic JP, Romero R, Espinoza J, Nien JK, Kim CJ, Mittal P et al (2008) Twin-to-twin transfusion syndrome: an antiangiogenic state? Am J Obstet Gynecol 198(4):382e1-8

    Google Scholar 

  17. Prefumo F, Pagani G, Fratelli N, Benigni A, Frusca T (2010) Increased concentrations of antiangiogenic factors in mirror syndrome complicating twin-to-twin transfusion syndrome. Prenat Diagn 30(4):378–379

    PubMed  Google Scholar 

  18. Romero R, Chaiworapongsa T, Erez O, Tarca AL, Gervasi MT, Kusanovic JP et al (2010) An imbalance between angiogenic and anti-angiogenic factors precedes fetal death in a subset of patients: results of a longitudinal study. J Matern Fetal Neonatal Med 23(12):1384–1399

    Article  PubMed Central  PubMed  Google Scholar 

  19. Gomez-Arriaga PI, Herraiz I, Lopez-Jimenez EA, Gomez-Montes E, Denk B, Galindo A (2013) Uterine artery Doppler and sFlt-1/PlGF ratio: usefulness in diagnosis of pre-eclampsia. Ultrasound Obstet Gynecol 41(5):530–537

    Article  CAS  PubMed  Google Scholar 

  20. Kleinrouweler CE, Wiegerinck MM, Ris-Stalpers C, Bossuyt PM, van der Post JA, von Dadelszen P et al (2012) Accuracy of circulating placental growth factor, vascular endothelial growth factor, soluble fms-like tyrosine kinase 1 and soluble endoglin in the prediction of pre-eclampsia: a systematic review and meta-analysis. BJOG 119(7):778–787

    Article  CAS  PubMed  Google Scholar 

  21. Livingston JC, Haddad B, Gorski LA, Neblett P, Ahokas RA, Ramsey R et al (2001) Placenta growth factor is not an early marker for the development of severe preeclampsia. Am J Obstet Gynecol 184(6):1218–1220

    Article  CAS  PubMed  Google Scholar 

  22. Widmer M, Villar J, Benigni A, Conde-Agudelo A, Karumanchi SA, Lindheimer M (2007) Mapping the theories of preeclampsia and the role of angiogenic factors: a systematic review. Obstet Gynecol 109(1):168–180

    Article  CAS  PubMed  Google Scholar 

  23. Taylor RN, Grimwood J, Taylor RS, McMaster MT, Fisher SJ, North RA (2003) Longitudinal serum concentrations of placental growth factor: evidence for abnormal placental angiogenesis in pathologic pregnancies. Am J Obstet Gynecol 188(1):177–182

    Article  CAS  PubMed  Google Scholar 

  24. Brancaccio P, Lippi G, Maffulli N (2010) Biochemical markers of muscular damage. Clin Chem Lab Med CCLM/FESCC 48(6):757–767

    CAS  Google Scholar 

  25. Cerdeira AS, Karumanchi SA (2012) Angiogenic factors in preeclampsia and related disorders. Cold Spring Harb Perspect Med 2(11). doi:10.1101/cshperspect.a006585

  26. Ghosh SK, Raheja S, Tuli A, Raghunandan C, Agarwal S (2012) Serum PLGF as a potential biomarker for predicting the onset of preeclampsia. Arch Gynecol Obstet 285(2):417–422

    Article  CAS  PubMed  Google Scholar 

  27. Powers RW, Jeyabalan A, Clifton RG, Van Dorsten P, Hauth JC, Klebanoff MA et al (2010) Soluble fms-Like tyrosine kinase 1 (sFlt1), endoglin and placental growth factor (PlGF) in preeclampsia among high risk pregnancies. PLoS One 5(10):e13263

    Article  PubMed Central  PubMed  Google Scholar 

  28. Llurba E, Marsal G, Sanchez O, Dominguez C, Alijotas-Reig J, Carreras E et al (2012) Angiogenic and antiangiogenic factors before and after resolution of maternal mirror syndrome. Ultrasound Obstet Gynecol 40(3):367–369

    Article  CAS  PubMed  Google Scholar 

  29. Goa S, Mimura K, Kakigano A, Tomimatsu T, Kinugasa-Taniguchi Y, Endo M et al (2013) Normalisation of angiogenic imbalance after intra-uterine transfusion for mirror syndrome caused by Parvovirus B19. Fetal Diagn Ther. doi:10.1159/000348778

    PubMed  Google Scholar 

  30. Poret-Bazin H, Simon EG, Bleuzen A, Dujardin PA, Patat F, Perrotin F (2013) Decrease of uteroplacental blood flow after feticide during second-trimester pregnancy termination with complete placenta previa: quantitative analysis using contrast-enhanced ultrasound imaging. Placenta 34(11):1113–1115

    Article  CAS  PubMed  Google Scholar 

  31. Ruano R, Kondo MM, Bunduki V, Rodeck C, Zugaib M (2006) Follow-up of uteroplacental vascularization after feticide in third-trimester therapeutic termination of pregnancy with complete placenta previa. Ultrasound Obstet Gynecol 27(4):463–465

    Article  CAS  PubMed  Google Scholar 

  32. De Falco S (2012) The discovery of placenta growth factor and its biological activity. Exp Mol Med 44(1):1–9

    Article  PubMed Central  PubMed  Google Scholar 

  33. Andraweera PH, Dekker GA, Roberts CT (2012) The vascular endothelial growth factor family in adverse pregnancy outcomes. Hum Reprod Update 18(4):436–457

    Article  CAS  PubMed  Google Scholar 

  34. Kendall RL, Wang G, Thomas KA (1996) Identification of a natural soluble form of the vascular endothelial growth factor receptor, FLT-1, and its heterodimerization with KDR. Biochem Biophys Res Commun 226(2):324–328

    Article  CAS  PubMed  Google Scholar 

  35. Nagamatsu T, Fujii T, Kusumi M, Zou L, Yamashita T, Osuga Y et al (2004) Cytotrophoblasts up-regulate soluble fms-like tyrosine kinase-1 expression under reduced oxygen: an implication for the placental vascular development and the pathophysiology of preeclampsia. Endocrinology 145(11):4838–4845

    Article  CAS  PubMed  Google Scholar 

  36. Molvarec A, Gullai N, Stenczer B, Fugedi G, Nagy B, Rigo J Jr (2013) Comparison of placental growth factor and fetal flow Doppler ultrasonography to identify fetal adverse outcomes in women with hypertensive disorders of pregnancy: an observational study. BMC Pregnancy Childbirth 13:161

    Article  PubMed Central  PubMed  Google Scholar 

  37. Beharier O, Shusterman E, Eshcoli T, Szaingurten-Solodkin I, Aricha-Tamir B, Weintraub AY et al (2014) Detection of S100B in maternal blood before and after fetal death. Prenat Diagn 34(1):94–97

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was sponsored by the “Medical Research during residency” program fund granted by the Faculty of Health Sciences, Ben-Gurion University of the Negev, and Soroka University Medical Center.

Conflict of interest

The authors declare that they have no conflict of interest. The authors are responsible for study design, the collection, analysis and interpretation of data, the writing of the report, and the decision to submit the article for publication.

Ethical standard

The study protocol was approved by the Ethics Committee of Soroka University Medical Center (protocol number: 0236-11-SOR) in accordance with the Helsinki declaration, and participants gave informed and signed consent. Feticide was approved by the local ethical committee as authorized by the Ministry of Health of Israel.

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    Authors and Affiliations

    1. Department of Obstetrics and Gynecology, Soroka University Medical Center and Ben-Gurion University of the Negev, Beer-Sheva, Israel

      Ofer Beharier, Adi Y. Weintraub, Eyal Sheiner & Reli Hershkovitz

    2. Department of Physiology and Cell Biology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel

      Eden Shusterman, Irit Szaingurten-Solodkin, Shani S. Swissa & Daniel Gitler

    3. Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel

      Daniel Gitler

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    1. Ofer Beharier
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    Correspondence to Ofer Beharier.

    Additional information

    O. Beharier and E. Shusterman equally contributed to this paper.

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    Beharier, O., Shusterman, E., Szaingurten-Solodkin, I. et al. Placental growth factor concentration in maternal circulation decreases after fetal death: lessons from a case series study. Arch Gynecol Obstet 292, 1027–1032 (2015). https://doi.org/10.1007/s00404-015-3729-7

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    • DOI: https://doi.org/10.1007/s00404-015-3729-7

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