Prenatal Clinical Assessment of sFlt-1 (Soluble fms-like Tyrosine Kinase-1)/PlGF (Placental Growth Factor) Ratio as a Diagnostic Tool for Preeclampsia, Pregnancy-induced Hypertension, and Proteinuria.

Abstract

Background: Aim of the study was a critical assessment of the clinical validity of the prenatal determination of sFlt-1/PlGF for preeclampsia (PE), pregnancy-induced hypertension (PIH), and proteinuria. Our analysis was based on a specificity of 95 % and a sensitivity of 82 % for the prediction of preeclampsia, as described by Elecsys (Roche). Methods: In this retrospective study the ratio of the prenatal antiangiogenic factor sFlt-1 (soluble fms-like tyrosine kinase-1) to the proangiogenic factor PIGF (placental growth factor) was analyzed using the electrochemiluminescence immunoassay of Elecsys (Roche Diagnostics, Mannheim, Germany) in 173 pregnant women. Sixty-three women with PE, 34 women with PIH and 6women with proteinuria were compared to 72controls. On average, the sFlt-1/PlGF ratio was determined 8 (controls), 2.4 (PE), 3.2 (PIH) and 4.1 (proteinuria) weeks before delivery. The PE and PIH cases were further subdivided into early (< 34 weeks of gestation) and late (≥ 34 weeks of gestation) onset groups. Statistical data analysis was done using the usual descriptive statistics and logistic regression analysis. ROC curves were calculated, and the sensitivity, specificity, and negative and positive predictive value (NPV, PPV) were estimated for a threshold of 85. Results: Although the specificity of the sFlt-1/PlGF ratio was high for PE, the sensitivity was low (only 59.4 %), thus giving unsatisfying results for PE. The sensitivity only increased to 62.5 % for the early-onset PE group. Intriguingly, a high ratio was detected for the combination of IUGR (intrauterine growth restriction) and PE in the early-onset PE group (8 cases). In the control group, 4cases exceeded the cut-off value of 85 but showed no clinical signs of PE and the birth was unremarkable. In summary, we found that the sFlt-1/PIGF ratio could not be used as a predictive test for preeclampsia but rather as an indicator for the development and estimation of the severity of PE. Thus, the test is less suitable for the reliable exclusion of PE in routine clinical practice. Recommendation: The determination of the sFlT-1/PlGF ratio is only one element for PE diagnosis in addition to the measurement of blood pressure, proteinuria, ultrasound and Doppler.