Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

First-trimester serum soluble fms-like tyrosine kinase-1, free vascular endothelial growth factor, placental growth factor and uterine artery Doppler in preeclampsia

Abstract

Objective:

To compare the first-trimester serum concentrations of soluble fms-like tyrosine kinase-1 (sFlt-1), free vascular endothelial growth factor (free-VEGF), placental growth factor (PlGF), and uterine artery pulsatility index (PI) in women who later developed preeclampsia (PE).

Study Design:

Prospectively collected maternal serum samples were evaluated for sFlt-1, free VEGF, and PlGF levels in 63 cases who later developed PE compared with 252 unaffected controls. Serum levels of these angiogenic factors were measured using Quantikine immunoassays. Both univariate and multivariate analyses were used to evaluate the association between angiogenic factors and PE. The relationship between the angiogenic factors and mean maternal uterine artery PI was also evaluated.

Result:

Maternal serum sFlt-1 levels were not significantly different between the cases and controls. Mean free-VEGF levels were significantly higher in women destined to develop PE compared with the controls (P=0.04), and mean PlGF levels were significantly lower in women who later developed PE (P=0.01). There was no significant correlation between maternal mean uterine artery PI and angiogenic factors evaluated. Receiver-operating characteristic curves revealed that none of the factors were clinically useful for prediction in the first trimester of PE.

Conclusion:

Despite some significant differences in the first-trimester serum levels of angiogenic factors, our models suggest that these factors are not clinically useful for prediction in women who later developed PE.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Sibai B, Dekker G, Kupferminc M . Preeclampsia. Lancet 2005; 365: 785–799.

    Article  PubMed  Google Scholar 

  2. Redman CW, Sargent IL . Latest advances in understanding preeclampsia. Science 2005; 308: 1592–1594.

    Article  CAS  PubMed  Google Scholar 

  3. 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: 649–658.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Sugimoto H, Hamano Y, Charytan D, Cosgrove D, Kieran M, Sudhakar A et al. Neutralization of circulating vascular endothelial growth factor (VEGF) by anti-VEGF antibodies and soluble VEGF receptor 1 (sFlt-1) induces proteinuria. J Biol Chem 2003; 278: 12605–12608.

    Article  CAS  PubMed  Google Scholar 

  5. Akolekar R, de Cruz J, Foidart JM, Munaut C, Nicolaides KH . Maternal plasma soluble fms-like tyrosine kinase-1 and free vascular endothelial growth factor at 11 to 13 weeks of gestation in preeclampsia. Prenat Diagn 2010; 30: 191–197.

    Article  CAS  PubMed  Google Scholar 

  6. Baumann MU, Bersinger NA, Mohaupt MG, Raio L, Gerber S, Surbek DV . First trimester serum levels of soluble endoglin and soluble fms like tyrosine kinase-1 as first-trimester markers for late-onset preeclampsia. Am J Obstet Gynecol 2008; 199: 266.e1–266.e6.

    Article  Google Scholar 

  7. 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: 279–287.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. 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.e1–239.e6.

    Article  Google Scholar 

  9. 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: 672–683.

    Article  CAS  PubMed  Google Scholar 

  10. 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: 137–142.

    Article  CAS  PubMed  Google Scholar 

  11. Myatt L, Clifton RG, Roberts JM, Spong CY, Hauth JC, Varner MW et alEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network. First-trimester prediction of preeclampsia in nulliparous women at low risk. Obstet Gynecol 2012; 119: 1234–1242.

    Article  PubMed Central  PubMed  Google Scholar 

  12. Forest JC, Charland M, Massé J, Bujold E, Rousseau F, Lafond J et al. Candidate biochemical markers for screening of pre-eclampsia in early pregnancy. Clin Chem Lab Med 2012; 50: 973.

    Article  CAS  PubMed  Google Scholar 

  13. Napolitano R, Melchiorre K, Arcangeli T, Dias T, Bhide A, Thilaganathan B . Screening for pre-eclampsia by using changes in uterine artery Doppler indices with advancing gestation. Prenat Diagn 2012; 32: 180–184.

    Article  PubMed  Google Scholar 

  14. Goetzinger KR, Cahill AG, Kemna J, Odibo L, Macones GA, Odibo AO . First-trimester prediction of preterm birth using ADAM12, PAPP-A, uterine artery Doppler, and maternal characteristics. Prenat Diagn 2012; 32: 1002–1007.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. American College of Obstetricians and Gynecologists. Diagnosis and management of preeclampsia and eclampsia. American College of Obstetricians and Gynecologists: Washington, DC, USA, 2002 ACOG practice bulletin no. 33.

  16. Alexander GR, Himes JH, Kaufman RB, Mor J, Kogan MA . United States national reference for fetal growth. Obstet Gynecol 1996; 87: 163–1.

    Article  CAS  PubMed  Google Scholar 

  17. Smith GC, Crossley JA, Aitken DA, Jenkins N, Lyall F, Cameron AD et al. Circulating angiogenic factors in early pregnancy and the risk of preeclampsia, intrauterine growth restriction, spontaneous preterm birth, and stillbirth. Obstet Gynecol 2007; 109: 1316–1324.

    Article  CAS  PubMed  Google Scholar 

  18. Coolman M, Timmermans S, de Groot CJ, Russcher H, Lindemans J, Hofman A et al. Angiogenic and fibrinolytic factors in blood during the first half of pregnancy and adverse pregnancy outcomes. Obstet Gynecol 2012; 119: 1190–1200.

    Article  PubMed  Google Scholar 

  19. Lyall F, Greer IA, Boswell F, Fleming R . Suppression of serum vascular endothelial growth factor immunoreactivity in normal pregnancy and in pre-eclampsia. Br J Obstet Gynaecol 1997; 104: 223–228.

    Article  CAS  PubMed  Google Scholar 

  20. Buhimschi CS, Magloire L, Funai E, Norwitz ER, Kuczynski E, Martin R et al. Fractional excretion of angiogenic factors in women with severe preeclampsia. Obstet Gynecol 2006; 107: 1103–1113.

    Article  PubMed  Google Scholar 

  21. Akolekar R, Zaragoza E, LCY Poon, Pepes S, Nicolaides KH . Maternal serum placental growth factor (PlGF) at 11 to 13 weeks of gestation in hypertensive disorders of pregnancy. Ultrasound Obstet Gynecol 2008; 32: 732–739.

    Article  CAS  PubMed  Google Scholar 

  22. Poon LC, Akolekar R, Lachmann R, Beta J, Nicolaides KH . Hypertensive disorders in pregnancy: screening by biophysical and biochemical markers at 11–13 weeks. Ultrasound Obstet Gynecol 2010; 35: 662–670.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by a Grant from the American Heart Association (#12GRNT10990002) to SKE.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to A O Odibo.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Odibo, A., Rada, C., Cahill, A. et al. First-trimester serum soluble fms-like tyrosine kinase-1, free vascular endothelial growth factor, placental growth factor and uterine artery Doppler in preeclampsia. J Perinatol 33, 670–674 (2013). https://doi.org/10.1038/jp.2013.33

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jp.2013.33

Keywords

This article is cited by

Search

Quick links