Research
Obstetrics
An automated method for the determination of the sFlt-1/PIGF ratio in the assessment of preeclampsia

https://doi.org/10.1016/j.ajog.2009.09.016Get rights and content

Objective

The angiogenic and antiangiogenic factors soluble fms-like tyrosine kinase (sFlt)-1 and placental growth factor (PIGF) have been implicated in the mechanisms of disease responsible for preeclampsia (PE). Moreover, it has been proposed that the concentrations of these markers in maternal serum/plasma may have predictive value. This study evaluates a newly developed Elecsys (Roche, Penzberg, Germany) assay for sFlt-1 and PIGF and tests the value of the sFlt-1/PIGF ratio in the assessment of PE.

Study Design

This multicenter case-control study included 351 patients: 71 patients with PE and 280 gestational age-matched control subjects from 5 European study centers. A total of 595 serum samples were measured for sFlt-1 and PIGF using an automated platform.

Results

Maternal serum concentrations of sFlt-1 and PIGF significantly separated healthy women and women with PE. The sFlt-1/PIGF ratio had an area under the receiver operating characteristic curve of 0.95. The best performance was obtained in the identification of early-onset PE (area under the receiver operating characteristic curve of 0.97).

Conclusion

Measurement of sFlt-1 and PIGF and calculation of sFlt-1/PIGF ratio can be performed quickly and in a platform available in clinical laboratories. This is a substantial step forward in bringing the determination of these analytes to clinical practice in obstetrics. We propose that sFlt-1, PIGF, and sFlt-1/PIGF ratio may be of value in the prediction of PE and in the differential diagnosis of patients with atypical presentations of PE, and perhaps in the differential diagnosis of women with chronic hypertension suspected to develop superimposed PE.

Section snippets

Study population

Singleton pregnancies were enrolled at 5 participating European medical centers. An identical study protocol and data collection form was used at each center. The local ethics committees and institutional review boards approved the procedure, and all subjects gave their written, informed consent before participation. Background data on the patients were provided by the study centers in form of a completed case report form. A total of 351 individuals were enrolled in the study: 280 singleton

Demographic and clinical characteristics of the population

For the reference range study arm a total of 280 patients were included. For the case-control study arm 71 women with clinical PE and 268 women with uneventful pregnancies were included. No significant differences in age, gestational age at enrollment, or ethnical origin were observed. Women with PE had a higher systolic and diastolic blood pressure, had a lower mean birthweight of the neonate, and were less likely to smoke than normotensive women. The results are listed in Table 1.

Reference range for sFlt-1, PIGF, and sFlt-1/PIGF ratio in normal pregnancies using the Elecsys assay system

To assess

Comment

We report a new automated method for the measurement of sFlt-1 and PIGF using a commercially available immunoassay platform. A reference range for the determination of these analytes, as well as the sFlt-1/PIGF ratio as a function of gestational age, is reported. Moreover, we provide evidence that the serum concentrations of these analytes and the sFlt-1/PIGF ratio are significantly different in women with PE than in healthy pregnant women. The automated tests will allow a fast and

References (42)

  • C.J. Robinson et al.

    Evaluation of placenta growth factor and soluble Fms-like tyrosine kinase 1 receptor levels in mild and severe preeclampsia

    Am J Obstet Gynecol

    (2006)
  • M. Noris et al.

    Mechanisms of disease: pre-eclampsia

    Nat Clin Pract Nephrol

    (2005)
  • J.M. Roberts et al.

    Summary of the NHLBI working group on research on hypertension during pregnancy

    Hypertens Pregnancy

    (2003)
  • ACOG practice bulletin no. 33Diagnosis and management of preeclampsia and eclampsia, January 2002

    Obstet Gynecol

    (2002)
  • B.M. Sibai et al.

    Diagnosis and management of atypical preeclampsia-eclampsia

    Am J Obstet Gynecol

    (2009)
  • ACOG committee opinion: antenatal corticosteroid therapy for fetal maturation

    Int J Gynaecol Obstet

    (2002)
  • L.J. Vatten et al.

    Changes in circulating level of IGF-I and IGF-binding protein-1 from the first to second trimester as predictors of preeclampsia

    Eur J Endocrinol

    (2008)
  • T.A. Moore Simas et al.

    Angiogenic factors for the prediction of preeclampsia in high-risk women

    Am J Obstet Gynecol

    (2007)
  • E. Shibata 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)
  • S.E. Maynard 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)
  • T. Chaiworapongsa et al.

    Evidence supporting a role for blockade of the vascular endothelial growth factor system in the pathophysiology of preeclampsia; young investigator award

    Am J Obstet Gynecol

    (2004)
  • Cited by (0)

    This study was sponsored by Roche, Penzberg, Germany.

    Cite this article as: Verlohren S, Galindo A, Schlembach D, 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.

    View full text