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Licensed Unlicensed Requires Authentication Published by De Gruyter February 21, 2014

New biomarkers in diagnosis of early onset preeclampsia and imminent delivery prognosis

  • Indira Álvarez-Fernández , Belén Prieto , Verónica Rodríguez , Yolanda Ruano , Ana I. Escudero and Francisco V. Álvarez EMAIL logo

Abstract

Background: Several studies have revealed a high soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF) ratio in preeclamptic women. However, its role in patients with suspected preeclampsia (PE) at triage in the emergency department remains an issue and a controversial unique cutpoint of 85 has been proposed regardless of gestational age. A new cutpoint for sFlt-1/PlGF ratio was investigated to rule out PE at obstetric triage, and to assess its prognostic value for risk of imminent delivery.

Methods: Blood samples from 257 pregnant women with suspected PE were obtained at obstetric triage admission. Serum PlGF and sFlt-1 were measured by an electrochemoluminiscence immunoassay (ECLIA) on the immunoanalyzer Cobas e601 (Roche Diagnostics) and the corresponding ratio was calculated. Final outcomes (mainly development of PE) were reviewed and time between clinical presentation and delivery was calculated.

Results: The best ratio cutpoint to diagnose PE changed according to gestational age: 23 (92.0% sensitivity, 81.1% specificity) and 45 (83.7% sensitivity, 72.6% specificity) for women <34 and ≥34 weeks’ gestation, respectively. Furthermore, sFlt-1/PlGF ratio inversely correlated with time elapsed between clinical presentation and delivery, and a cutpoint of 178 could predict complications such as imminent delivery or fetal/neonatal death with a sensitivity of 70.6% and a specificity of 97.8%.

Conclusions: The new cut-off values for the sFlt-1/PlGF ratio adjusted by the gestational age at clinical presentation can be used to rule out PE at obstetric triage and to predict imminent delivery with better accuracy than the cutpoint currently accepted.


Corresponding author: Francisco V. Álvarez, PhD, Hospital Universitario Central de Asturias, C/ Celestino Villamil, s/n 33006 Oviedo, Spain, Phone/Fax: +34 98 5108073, E-mail:

Acknowledgments

Roche Diagnostics collaborated with the present work by supplying the testing kits for PlGF and sFlt-1 determinations.

Conflict of interest statement

Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article. Research support played no role in thestudy design; in the collection, analysis, and interpretationof data; in the writing of the report; or in the decision tosubmit the report for publication.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

References

1. Steegers EA, Von Dadelszen P, Duvekot JJ, Pijnenborg R. Pre-eclampsia. Lancet 2010;376:631–44.10.1016/S0140-6736(10)60279-6Search in Google Scholar

2. Sibai B, Dekker G, Kupferminc M. Pre-eclampsia. Lancet 2005;365:785–99.10.1016/S0140-6736(05)17987-2Search in Google Scholar

3. Kleinrouweler CE, Wiegerinck MM, Ris-Stalpers C, Bossuyt PM, Van der Post JA, Von Dadelszen P, et al. 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 2012;119:778–87.10.1111/j.1471-0528.2012.03311.xSearch in Google Scholar PubMed

4. Uzan J, Carbonnel M, Piconne O, Asmar R, Ayoubi J-M. Pre-eclampsia: pathophysiology, diagnosis, and management. Vasc Health Risk Manag 2011;7:467–74.Search in Google Scholar

5. American College of Obstetricians and Gynecologists. ACOG – antenatal corticosteroid therapy for fetal maturation. Am J Obstet Gynecol 2011;117:422–4.10.1097/AOG.0b013e31820eee00Search in Google Scholar PubMed

6. Sibai BM. Magnesium sulfate prophylaxis in preeclampsia: lessons learned from recent trials. Am J Obstet Gynecol 2004;190:1520–6.10.1016/j.ajog.2003.12.057Search in Google Scholar PubMed

7. ACOG practice bulletin. Diagnosis and management of preeclampsia and eclampsia. Am J Obstet Gynecol 2002;77:67–75.Search in Google Scholar

8. Milne F, Redman C, Walker J, Baker P, Black R, Blincowe J, et al. Assessing the onset of pre-eclampsia in the hospital day unit: summary of the pre-eclampsia guideline (PRECOG II). Br Med J 2009;339:b3129.10.1136/bmj.b3129Search in Google Scholar PubMed

9. Espinoza J. Recent biomarkers for the identification of patients at risk for preeclampsia: the role of uteroplacental ischemia. Expert Opin Med Diagn 2012;6:121–30.10.1517/17530059.2012.659726Search in Google Scholar PubMed

10. Maynard S, Epstein FH, Karumanchi SA. Preeclampsia and angiogenic imbalance. Annu Rev Med 2008;59:61–78.10.1146/annurev.med.59.110106.214058Search in Google Scholar PubMed

11. Maynard SE, Min J-Y, Merchan J, Lim K-H, 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;111:649–58.10.1172/JCI17189Search in Google Scholar PubMed PubMed Central

12. Koga K, Osuga Y, Yoshino O, Hirota Y, Ruimeng X, Hirata T, et al. Elevated serum soluble vascular endothelial growth factor receptor 1 (sVEGFR-1) levels in women with preeclampsia. J Clin Endocrinol Metab 2003;88:2348–51.10.1210/jc.2002-021942Search in Google Scholar PubMed

13. Levine RJ, Maynard SE, Qian C, Lim K-H, England LJ, Yu KF, et al. Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med 2004;350:672–83.10.1056/NEJMoa031884Search in Google Scholar PubMed

14. Romero R, Nien JK, Espinoza J, Todem D, Fu W, Chung H, et al. 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 2008;21:9–23.10.1080/14767050701830480Search in Google Scholar PubMed PubMed Central

15. 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.e1–11.10.1016/j.ajog.2009.09.016Search in Google Scholar PubMed

16. 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;33:422–7.10.1038/hr.2010.15Search in Google Scholar PubMed

17. Sunderji S, Gaziano E, Wothe D, Rogers LC, Sibai B, Karumanchi SA, et al. Automated assays for sVEGF R1 and PlGF as an aid in the diagnosis of preterm preeclampsia: a prospective clinical study. Am J Obstet Gynecol 2010;202:40.e1–7.10.1016/j.ajog.2009.07.025Search in Google Scholar PubMed

18. 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;125:911–9.10.1161/CIRCULATIONAHA.111.054361Search in Google Scholar PubMed PubMed Central

19. Chaiworapongsa T, Romero R, Savasan ZA, Kusanovic JP, Ogge G, Soto E, et al. Maternal plasma concentrations of angiogenic/anti-angiogenic factors are of prognostic value in patients presenting to the obstetrical triage area with the suspicion of preeclampsia. J Matern Fetal Neonatal Med 2011;24:1187–207.10.3109/14767058.2011.589932Search in Google Scholar PubMed PubMed Central

20. Chaiworapongsa T, Romero R, Korzeniewski SJ, Cortez JM, Pappas A, Tarca AL, et al. Plasma concentrations of angiogenic/anti-angiogenic factors have prognostic value in women presenting with suspected preeclampsia to the obstetrical triage area: a prospective study. J Matern Fetal Neonatal Med 2014;27:132–44.10.3109/14767058.2013.806905Search in Google Scholar PubMed PubMed Central

21. Raymond D, Peterson E. A critical review of early-onset and late-onset preeclampsia. Obstet Gynecol Surv 2011;66: 497–506.10.1097/OGX.0b013e3182331028Search in Google Scholar PubMed

22. Crispi F, Domínguez C, Llurba E, Martín-Gallán P, Cabero L, Gratacós E. Placental angiogenic growth factors and uterine artery Doppler findings for characterization of different subsets in preeclampsia and in isolated intrauterine growth restriction. Am J Obstet Gynecol 2006;195:201–7.10.1016/j.ajog.2006.01.014Search in Google Scholar PubMed

23. Wallner W, Sengenberger R, Strick R, Strissel PL, Meurer B, Beckmann MW, et al. Angiogenic growth factors in maternal and fetal serum in pregnancies complicated by intrauterine growth restriction. Clin Sci (Lond) 2007;112:51–7.10.1042/CS20060161Search in Google Scholar PubMed

24. Åsvold BO, Vatten LJ, Romundstad PR, Jenum P a, Karumanchi SA, Eskild A. Angiogenic factors in maternal circulation and the risk of severe fetal growth restriction. Am J Epidemiol 2011;173:630–9.10.1093/aje/kwq373Search in Google Scholar PubMed

25. 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;209:53.e1–9.10.1016/j.ajog.2013.03.017Search in Google Scholar PubMed

26. Maynard SE, Moore Simas TA, Solitro MJ, Rajan A, Crawford S, Soderland P, et al. Circulating angiogenic factors in singleton vs multiple-gestation pregnancies. Am J Obstet Gynecol 2008;198:200.e1–7.10.1016/j.ajog.2007.08.042Search in Google Scholar PubMed

27. Powers RW, Jeyabalan A, Clifton RG, Van Dorsten P, Hauth JC, Klebanoff MA, et al. Soluble fms-Like tyrosine kinase 1 (sFlt1), endoglin and placental growth factor (PlGF) in preeclampsia among high risk pregnancies. PLoS One 2010;5:e13263.10.1371/journal.pone.0013263Search in Google Scholar PubMed PubMed Central

28. Bdolah Y, Lam C, Rajakumar A, Shivalingappa V, Mutter W, Sachs BP, et al. Twin pregnancy and the risk of preeclampsia: bigger placenta or relative ischemia? Am J Obstet Gynecol 2008;198:428.e1–6.10.1016/j.ajog.2007.10.783Search in Google Scholar PubMed

29. Mackay AP, Berg CJ, Atrash HK. Pregnancy-related mortality from preeclampsia and eclampsia. Obstet Gynecol 2001;97:533–8.Search in Google Scholar

30. Hirashima C, Ohkuchi A, Takahashi K, Suzuki H, Yoshida M, Ohmaru T, et al. Gestational hypertension as a subclinical preeclampsia in view of serum levels of angiogenesis-related factors. Hypertens Res 2011;34:212–7.10.1038/hr.2010.212Search in Google Scholar PubMed

31. PlGF [package insert]. Roche Diagnostics GmbH, Mannheim, Germany; 2013-08,V 6.0.Search in Google Scholar

32. Lim JH, Kim SY, Park SY, Yang JH, Kim MY, Ryu HM. Effective prediction of preeclampsia by a combined ratio of angiogenesis-related factors. Obstet Gynecol 2008;111:1403–9.10.1097/AOG.0b013e3181719b7aSearch in Google Scholar PubMed

33. 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.e1–8.10.1016/j.ajog.2011.07.037Search in Google Scholar PubMed

Received: 2013-10-21
Accepted: 2014-1-6
Published Online: 2014-2-21
Published in Print: 2014-8-1

©2014 by Walter de Gruyter Berlin/Boston

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