Multicenter evaluation of the first automated Elecsys sFlt-1 and PlGF assays in normal pregnancies and preeclampsia

Schiettecatte, Johan; Russcher, Henk; Anckaert, Ellen; Mees, Marleen; Leeser, Brandon; Tirelli, Amedea Silvia; Fiedler, Georg Martin; Luthe, Hilmar; Denk, B.; Smitz, Johan

doi:10.1016/j.clinbiochem.2010.02.010

Cited by 93 publications

(60 citation statements)

References 13 publications

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“…Previous work from our group as well as from others has consistently shown that the automated measurement of sFlt-1, PlGF and the calculation of the sFlt-1/PlGF ratio is a reliable tool for the diagnosis of preeclampsia. 8,10,[13][14][15] We reported earlier a cutoff of 85 for the sFlt-1/PlGF ratio as an aid in diagnosis of preeclampsia regardless of the gestational week tested. This preliminary cutoff was based on a casecontrol cohort of 71 patients with preeclampsia and 280 control patients.…”

Section: Discussionmentioning

confidence: 99%

“…9 Various groups have shown that 1 single cutoff at 85 is not optimal for diagnosing preeclampsia or other hypertensive pregnancy disorders in all clinical settings. 14,19,20 The new gestational phase-specific 2 cutoffs allow maximized accuracy of diagnosis. A more precise diagnosis and gestational phase-dependent analysis might have future therapeutic consequences.…”

Section: Clinical Valuementioning

confidence: 99%

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New Gestational Phase–Specific Cutoff Values for the Use of the Soluble fms-Like Tyrosine Kinase-1/Placental Growth Factor Ratio as a Diagnostic Test for Preeclampsia

Verlohren

Herraı̀z²,

Lapaire³

et al. 2014

Hypertension

288

239

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Preeclampsia is a multisystem disorder in pregnancy. With an incidence of 2% to 5% of all pregnancies, it is a frequent pregnancy-related disease and a major cause of maternal and fetal morbidity and mortality.1 Preeclampsia is defined as the newonset of hypertension (≥140/90 mm Hg on 2 separate occasions ≥4 hours apart) and proteinuria (≥300 mg/24 h). 2 The simplicity of this definition contrasts with the complexity of the disease. The pathophysiology of preeclampsia is not conclusively resolved up to now. Early-onset preeclampsia, defined as the onset before 34 weeks of gestation, comprises the mal implantation of the placenta, insufficient spiral-artery remodeling, prevalently resulting in intrauterine growth restriction and an altered expression of placental proteins such as soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factors (PlGFs).3 In contrast, lateonset preeclampsia, defined as the onset after 34 weeks of gestation, is not necessarily accompanied by placental dysfunction 4 but angiogenic and antiangiogenic factors are also dysregulated, though to a less dramatic extent. 5 We and others have previously shown that the sFlt-1/PlGF ratio is elevated in patients with preeclampsia.6-10 The automated measurement of the sFlt-1/PlGF ratio detects early-onset preeclampsia with a sensitivity of 89% and a specificity of 97% when the single, gestation-wide cutoff of 85 is used. 8 Recently, Rana et al 9 have shown that in patients with signs and symptoms for the disease, an sFlt-1/PlGF ratio ≥85 predicts the occurrence of preeclampsia-related adverse maternal and fetal outcomes, Abstract-To establish gestational phase adapted cutoffs for the use of the soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) ratio as a diagnostic tool for preeclampsia in the clinical setting, a multicenter case-control study including a total of 1149 patients was performed. We report normal values of sFlt-1, PlGF, and the sFlt-1/PlGF ratio based on the analysis of a total of 877 patients with uneventful pregnancy outcome. A total of 234 patients with preeclampsia and a matched cohort consisting of 468 patients with normal pregnancy outcome were compared, and sFlt-1 and PlGF were measured on an automated platform. Separate cutoffs for the sFlt-1/PlGF ratio were determined for the early (20+0-33+6 weeks) and the late gestational phase (34+0 weeks-delivery). For each of the 2 gestational phases, 2 independent cutoffs framing an equivocal zone were determined: the first cutoff with focus on high sensitivity, and the second focusing on high specificity. Between 20+0 and 33+6 weeks, the cutoffs at ≤33 and ≥85 resulted in a sensitivity/specificity of 95%/94% and 88%/99.5%, respectively. An sFlt-1/PlGF ratio of ≤33 had the lowest likelihood of a negative test (0.05; 95% confidence interval, 0.02-0.13), whereas values ≥85 had the highest likelihood of a positive test (176; 95% confidence interval, 24.88-1245). After 34+0 weeks, the cutoffs at ≤33 and ≥110 yielded a sensitivity/specificity of 89.6%/73.1% ...

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Section: Discussionmentioning

confidence: 99%

Section: Clinical Valuementioning

confidence: 99%

New Gestational Phase–Specific Cutoff Values for the Use of the Soluble fms-Like Tyrosine Kinase-1/Placental Growth Factor Ratio as a Diagnostic Test for Preeclampsia

Verlohren

Herraı̀z²,

Lapaire³

et al. 2014

Hypertension

288

239

View full text Add to dashboard Cite

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“…7 Meanwhile fast and accurate assays working on existing diagnostic platforms, including a point-of-care assay, have been developed. 7,11,12,26,27 The diagnostic performance of the sFlt-1/PlGF ratio is better than that of the individual values of sFlt-1 and PlGF. 7,11 With a cutoff value of 85, the reported sensitivity and specificity of the sFlt-1/PlGF ratio are 89% and 97% (area under the receiver operating characteristic curve, 0.97) for preterm preeclampsia and 74% and 89% (area under the receiver operating characteristic curve, 0.87) for late-onset preeclampsia.…”

Section: Sflt-1/plgf Ratio As a Diagnostic Testmentioning

confidence: 99%

Differential Diagnosis of Preeclampsia

et al. 2012

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“…Measurement of angiogenic factors using automated assays (sFlt-1 and PlGF) has proven to be clinically useful for routine diagnosis of preeclampsia (Ohkuchi et al 2010;Schiettecatte et al 2010;Sunderji et al 2010;Verlohren et al 2010;Benton et al 2011;Knudsen et al 2012). Several groups have shown that sFlt-1 and free PlGF levels can be used to differentiate preeclampsia from diseases that mimic preeclampsia, such as chronic hypertension, gestational hypertension, kidney disease, and gestational thrombocytopenia (Salahuddin et al 2007;Sunderji et al 2010;Perni et al 2012;Rolfo et al 2012;Verdonk et al 2012).…”

Section: Angiogenic Factors As Biomarkersmentioning

confidence: 99%

Molecular Mechanisms of Preeclampsia

Cerdeira

2015

Cold Spring Harb Perspect Med

147

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Preeclampsia is a pregnancy-specific disease characterized by new onset hypertension and proteinuria after 20 wk of gestation. It is a leading cause of maternal and fetal morbidity and mortality worldwide. Exciting discoveries in the last decade have contributed to a better understanding of the molecular basis of this disease. Epidemiological, experimental, and therapeutic studies from several laboratories have provided compelling evidence that an antiangiogenic state owing to alterations in circulating angiogenic factors leads to preeclampsia. In this review, we highlight the role of key circulating antiangiogenic factors as pathogenic biomarkers and in the development of novel therapies for preeclampsia.

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Multicenter evaluation of the first automated Elecsys sFlt-1 and PlGF assays in normal pregnancies and preeclampsia

Cited by 93 publications

References 13 publications

New Gestational Phase–Specific Cutoff Values for the Use of the Soluble fms-Like Tyrosine Kinase-1/Placental Growth Factor Ratio as a Diagnostic Test for Preeclampsia

New Gestational Phase–Specific Cutoff Values for the Use of the Soluble fms-Like Tyrosine Kinase-1/Placental Growth Factor Ratio as a Diagnostic Test for Preeclampsia

Differential Diagnosis of Preeclampsia

Molecular Mechanisms of Preeclampsia

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