Rule-in and rule-out of pre-eclampsia using DELFIA Xpress PlGF 1-2-3 and sFlt-1: PlGF ratio

AbstractBackgroundThe management of potential pre-eclamptic patients using the soluble FMS-like tyrosine kinase 1 (sFlt-1)/ placental growth factor (PlGF) ratio is characterised by frequent false-positive results.MethodsA retrospective cohort study was conducted to identify and validate cut-off values, obtained using a machine learning model, for the sFlt-1/PlGF ratio and NT-proBNP that would be predictive of the absence or presence of early-onset pre-eclampsia (PE) in singleton pregnancies presenting at 24 to 33 + 6 weeks of gestation.ResultsFor the development cohort, we defined two sFlt-1/PlGF ratio cut-off values of 23 and 45 to rule out and rule in early-onset PE at any time between 24 and 33 + 6 weeks of gestation. Using an sFlt-1/PlGF ratio cut-off value of 23, the negative predictive value (NPV) for the development of early-onset PE was 100% (95% confidence interval [CI]: 99.5–100). The positive predictive value (PPV) of an sFlt-1/PlGF ratio >45 for a diagnosis of early-onset PE was 49.5% (95% CI: 45.8–55.6). When an NT-proBNP value >174 was combined with an sFlt-1/PlGF ratio >45, the PPV was 86% (95% CI: 79.2–92.6). In the validation cohort, the negative and positive values were very similar to those found for the development cohort.ConclusionsAn sFlt-1/PlGF ratio <23 rules out early-onset PE between 24 and 33 + 6 weeks of gestation at any time, with an NPV of 100%. An sFlt-1/PlGF ratio >45 with an NT-proBNP value >174 significantly enhances the probability of developing early-onset PE.

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Clinical Performance of The sFlt-1/PlGF Test For The Prediction of Preeclampsia Among Asymptomatic and Symptomatic Pregnant Women in Estonia: A Nested Case-Control Study

10.21203/rs.3.rs-148900/v1 ◽

2021 ◽

Author(s):

Ele Hanson ◽

Kristiina Rull ◽

Kaspar Ratnik ◽

Pille Vaas ◽

Pille Teesalu ◽

...

Keyword(s):

Pregnant Women ◽

Clinical Setting ◽

Gestational Hypertension ◽

High Reliability ◽

Late Gestation ◽

University Hospital ◽

Correct Prediction ◽

Ratio Test ◽

Plgf Ratio ◽

Rule Out

Abstract Background: Pre-eclampsia (PE) is a pregnancy complication manifesting as new-onset hypertension and other maternal organ dysfunction after 20th gestational weeks. The study aimed to evaluate the applicability and limitations of the maternal serum soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) test in a clinical setting for the prediction of PE among symptomatic and asymptomatic pregnant women. There is limited knowledge on the performance of this test in asymptomatic women and thus, its value for screening purposes to predict PE is not confidently settled.Methods: The study group comprised of 215 patients developing either PE (n=29) or gestational hypertension/proteinuria (n=22) or representing controls (n=164). Patients had been sampled within 180-291 gestational days in the presence (symptomatic, n=31) or absence (asymptomatic, n=216) of PE-alerting symptoms. Serum samples collected during prospective cohort study ’Happy Pregnancy’ at the Women’s Clinic, Tartu University Hospital, Estonia, and they were analyzed using the BRAHMS sFlt‑1 Kryptor/BRAHMS PlGF plus Kryptor PE ratio test (Thermo Fisher Scientific, Henningdorf, Germany). The results were interpreted using recommendations by Stepan et al 2015 Ultrasound Obstet Gynecol. Results: The assignment of ’Rule-out PE’ (sFlt-1/PlGF ratio <38) had a negative predictive value >99% for four weeks for both asymptomatic and symptomatic women. Among 29 sera assigned to the ‘Rule-in PE’(sFlt-1/PlGF >85/110), only 18 pregnancies (62.1%) eventually developed PE. For four weeks period, the overall PE detection rate was 83% for asymptomatic and 50% for symptomatic pregnancies. Pregnancies receiving false predictions of PE risk based on sFlt-1/PlGF ratio represented either cases with an isolated small-for-gestational age fetus or blood sampling after 34 gestational weeks.Conclusions: The first study in Estonian patients confirmed high reliability of the proposed cut-off value sFlt-1/PlGF <38 as a “Rule-out PE” cut-off value for two weeks in both symptomatic and asymptomatic pregnancies. The test’s limitation in our clinical setting appeared to be high false positive rate in pregnancies with other placental pathologies than PE or due to physiological increase in sFlt-1/PlGF in late gestation. For correct prediction of PE, more specific recommendations are urgently needed for the application and interpretation of the test in routine clinical practice.

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PIH23 BUDGET IMPACT ANALYSIS OF SFLT-1/PLGF RATIO TO HELP RULE-OUT PRE-ECLAPMSIA IN WOMEN PRESENTING WITH SUSPECTED PRE-ECLAMPSIA IN THE PRIVATE HEALTHCARE SYSTEM IN BRAZIL

Value in Health ◽

10.1016/j.jval.2019.04.823 ◽

2019 ◽

Vol 22 ◽

pp. S186

Author(s):

R. Ho ◽

M.M. Sebastião ◽

A. Vassalli ◽

M. D'Innocenzo ◽

M. Nussbaum

Keyword(s):

Healthcare System ◽

Impact Analysis ◽

Budget Impact ◽

Budget Impact Analysis ◽

Private Healthcare ◽

Plgf Ratio ◽

Rule Out

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The Prognostic Value of Angiogenic Markers in Twin Pregnancies to Predict Delivery Due to Maternal Complications of Preeclampsia

Hypertension ◽

10.1161/hypertensionaha.120.14957 ◽

2020 ◽

Vol 76 (1) ◽

pp. 176-183 ◽

Cited By ~ 1

Author(s):

Julia Binder ◽

Pilar Palmrich ◽

Petra Pateisky ◽

Erkan Kalafat ◽

Lorenz Kuessel ◽

...

Keyword(s):

Predictive Value ◽

Predictive Accuracy ◽

Area Under The Curve ◽

Blood Sampling ◽

Maternal Complications ◽

Retrospective Data Analysis ◽

Twin Pregnancies ◽

Plgf Ratio ◽

Rule Out ◽

Singleton Pregnancies

The sFlt-1 (soluble fms-like tyrosine kinase-1), PlGF (placental growth factor), and their ratio are useful for predicting delivery because of preeclampsia in singleton pregnancies. Evidence on the utility of sFlt-1/PlGF ratio in twin pregnancies is lacking. We aimed to evaluate the predictive value of sFlt-1/PlGF ratio for delivery because of preeclampsia in twins. A retrospective data analysis of 164 twin pregnancies with suspected preeclampsia was performed. The sFlt-1/PlGF ratio, which was known to clinicians, was significantly higher in women who delivered within 1 and 2 weeks compared with those who did not (median: 98.9 and 84.2 versus 23.5 pg/mL, respectively; P <0.001). The area under the curve values sFlt-1/PlGF ratio levels were 0.88 (95% CI, 0.83–0.84) and 0.88 (95% CI, 0.83–0.93) for predicting delivery because of preeclampsia within 1 and 2 weeks of blood sampling, respectively. The predictive accuracy of sFlt-1/PlGF was independent of gestational age at sampling and chorionicity ( P >0.100 for interaction). The area under the curve values of sFlt-1/PlGF were significantly higher than for PlGF alone (mean 0.88 and 0.88 versus 0.81 and 0.80) for predicting delivery because of preeclampsia within 1 and 2 weeks of blood sampling ( P =0.055 and 0.001, respectively). sFlt-1/PlGF ratio lower than 38 was able to rule-out delivery within 1 and 2 weeks with a negative predictive value of 98.8% and 96.4% for delivery because of preeclampsia within 1 and 2 weeks, respectively. A cutoff of 38 is applicable for ruling out delivery because of preeclampsia in twin pregnancies.

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Short-Term Prediction of Preeclampsia in Chinese Women Using the Soluble fms-Like Tyrosine Kinase 1/Placental Growth Factor Ratio: A Sub-Analysis of the PROGNOSIS Asia Study

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.602560 ◽

2021 ◽

Vol 8 ◽

Author(s):

Jinsong Gao ◽

Xianghua Huang ◽

Wen Di ◽

Xiaojing Dong ◽

Wenli Gou ◽

...

Keyword(s):

Growth Factor ◽

Chinese Women ◽

Predictive Performance ◽

Placental Growth Factor ◽

Adverse Outcomes ◽

Short Term ◽

Term Prediction ◽

Short Term Prediction ◽

Plgf Ratio ◽

Rule Out

The diagnosis of preeclampsia in China currently relies on limited clinical signs and unspecific laboratory findings. These are inadequate predictors of preeclampsia development, limiting early diagnosis and appropriate management. Previously, the Prediction of Short-Term Outcome in Pregnant Women with Suspected Preeclampsia Study (PROGNOSIS) and PROGNOSIS Asia demonstrated that a soluble fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio of ≤38 can be used to rule out preeclampsia within 1 week, with negative predictive values of 99.3 and 98.6%, respectively. This is an exploratory sub-analysis of the Chinese cohort (n = 225) of the PROGNOSIS Asia study. The primary objectives were to assess the predictive performance of using the sFlt-1/PlGF ratio to rule out preeclampsia within 1 week and to rule in preeclampsia within 4 weeks. The sFlt-1/PlGF ratio was also examined for short-term prediction of fetal adverse outcomes, maternal adverse outcomes, and time to delivery. The overall prevalence of preeclampsia was 17.3%. With the use of an sFlt-1/PlGF ratio of ≤38, the negative predictive value for ruling out preeclampsia within 1 week was 97.3% [95% confidence interval (CI), 93.8–99.1], with a sensitivity of 64.3% and specificity of 85.3%. With the use of an sFlt-1/PlGF ratio of >38, the positive predictive value for ruling in preeclampsia within 4 weeks was 35.0% (95% CI, 20.6–51.7), with a sensitivity of 50.0% and specificity of 86.8%. In the analyses of the sFlt-1/PlGF ratio and fetal adverse outcomes, the area under the receiver operating characteristic curve was 92.8% (95% CI, 83.5–98.7) for ruling out fetal adverse outcomes within 1 week and 79.9% (95% CI, 68.1–90.3) for ruling in fetal adverse outcomes within 4 weeks. An sFlt-1/PlGF ratio of >38 increased the likelihood of imminent delivery 3.3-fold compared with a ratio of ≤38 [hazard ratio, 3.3 (95% CI, 2.1–5.1)]. This sub-analysis confirms the high predictive performance of the sFlt-1/PlGF ratio cutoff of 38 for short-term prediction of preeclampsia in Chinese women, which may help prevent unnecessary hospitalization of women with low risk of developing preeclampsia.

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8 The sFlt-1/PLGF ratio can rule out preeclampsia for up to four weeks in women with suspected preeclampsia

Pregnancy Hypertension ◽

10.1016/j.preghy.2016.08.009 ◽

2016 ◽

Vol 6 (3) ◽

pp. 140-141 ◽

Cited By ~ 6

Author(s):

Stefan Verlohren ◽

Elisa Llurba ◽

Frederic Chantraine ◽

Manu Vatish ◽

Anne Cathrine Staff ◽

...

Keyword(s):

Plgf Ratio ◽

Rule Out

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Use of the sFlt-1/PlGF ratio to rule out preeclampsia requiring delivery in women with suspected disease. Is the evidence reproducible?

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2017-0443 ◽

2018 ◽

Vol 56 (2) ◽

pp. 303-311 ◽

Cited By ~ 7

Author(s):

Enric Sabrià ◽

Paloma Lequerica-Fernández ◽

Paula Lafuente Ganuza ◽

Edwin Eguia Ángeles ◽

Ana I. Escudero ◽

...

Keyword(s):

Early Onset ◽

Pregnancy Termination ◽

Positive Likelihood Ratio ◽

Risk Pregnancy ◽

Published Evidence ◽

Ratio Determination ◽

Early Onset Preeclampsia ◽

Roche Diagnostics ◽

Plgf Ratio ◽

Rule Out

Abstract Background: Soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF) ratio has been proven to predict preeclampsia occurrence. Methods: Blood samples from 195 pregnant women with suspected preeclampsia were obtained at obstetric triage admission or from the high-risk pregnancy outpatient office. Serum PlGF and sFlt-1 were measured by an electrochemiluminescence immunoassay (ECLIA) on the immunoanalyser Cobas e601 (Roche Diagnostics) and the corresponding ratio was calculated. Final outcomes were reviewed by an independent obstetrician. Only the first determination was considered. Results: A sFlt-1/PlGF ratio of 38 or lower ruled out the need for pregnancy termination due to preeclampsia in the subsequent week with a negative predictive value (NPV) of 99.1% (sensitivity 97.1% and specificity 67.5%). None of the 76 pregnancies with first determination of an sFlt-1/PlGF ratio of 38 or lower between 24 and 34 weeks of gestation delivered due to early-onset preeclampsia. Positive likelihood ratio (PLR) of an sFlt-1/PlGF ratio above 38 for prediction of pregnancy termination due to preeclampsia within 4 weeks is analogous to published evidence. Conclusions: Between 24 and 34 weeks of gestation, no subsequent determination was needed to completely rule out early-onset preeclampsia when the first sFlt-1/PlGF ratio determination was 38 or lower in singleton pregnancies with signs or symptoms of this syndrome. These findings, if confirmed, will reduce costs and facilitate the implementation of the sFlt-1/PlGF ratio in women with clinical suspicion of preeclampsia in the third trimester.

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Short-term prediction of preeclampsia using the sFlt-1/PlGF ratio: a subanalysis of pregnant Japanese women from the PROGNOSIS Asia study

Hypertension Research ◽

10.1038/s41440-021-00629-x ◽

2021 ◽

Author(s):

Akihide Ohkuchi ◽

Shigeru Saito ◽

Tatsuo Yamamoto ◽

Hisanori Minakami ◽

Hisashi Masuyama ◽

...

Keyword(s):

Predictive Value ◽

Cox Regression ◽

Japanese Women ◽

Adverse Outcomes ◽

Short Term ◽

Multicenter Studies ◽

Term Prediction ◽

Short Term Prediction ◽

Plgf Ratio ◽

Rule Out

AbstractTwo prospective multicenter studies demonstrated that a soluble fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio cutoff of ≤38 can rule out preeclampsia within 1 week with a negative predictive value (NPV) of 99.3% (PROGNOSIS) and 98.6% (PROGNOSIS Asia). We report a subanalysis of the Japanese cohort from the PROGNOSIS Asia study. Pregnant women with suspected preeclampsia between gestational weeks 18 + 0 days and 36 + 6 days were enrolled at eight Japanese sites. Primary objectives: Assess the performance of the Elecsys® sFlt-1/PlGF ratio cutoff ≤38 to rule out preeclampsia within 1 week and of the cutoff >38 to rule in preeclampsia within 4 weeks. Key secondary objectives: Prediction of maternal and fetal adverse outcomes (MAOs/FAOs) and their relationship with duration of pregnancy. Of 192 women enrolled, 180 (93.8%)/175 (91.1%) were evaluable for primary/combined endpoint analyses. Overall preeclampsia prevalence was 13.3%. A sFlt-1/PlGF ratio of ≤38 provided an NPV of 100% (95% confidence interval [CI], 97.5–100) for ruling out preeclampsia within 1 week, and a ratio of >38 provided a positive predictive value of 32.4% (95% CI, 18.0–49.8) for ruling in preeclampsia within 4 weeks. The area under the curve for the prediction of preeclampsia/maternal/fetal adverse outcomes within 1 week was 94.2% (95% CI, 89.3–97.8). After adjusting for gestational age and final preeclampsia status, Cox regression indicated a 2.8-fold greater risk of imminent delivery for women with a sFlt-1/PlGF ratio >38 versus ≤38. This subanalysis of Japanese women with suspicion of preeclampsia showed high predictive value for a Elecsys sFlt-1/PlGF ratio cutoff of 38 for short-term prediction of preeclampsia.

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A rapid method for the direct identification of paramyxovirus in canine CSF by ultracentrifugation and negative staining as a rule out for distemper

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100160522 ◽

1990 ◽

Vol 48 (3) ◽

pp. 594-595

Author(s):

W.L. Steffens ◽

M.B. Ard ◽

C.E. Greene ◽

A. Jaggy

Keyword(s):

Subacute Sclerosing Panencephalitis ◽

Clinical Signs ◽

Viral Disease ◽

Etiologic Agent ◽

Mucosal Inflammation ◽

Worldwide Distribution ◽

Negative Stain ◽

Viral Particles ◽

Systemic Manifestations ◽

Rule Out

Canine distemper is a multisystemic contagious viral disease having a worldwide distribution, a high mortality rate, and significant central neurologic system (CNS) complications. In its systemic manifestations, it is often presumptively diagnosed on the basis of clinical signs and history. Few definitive antemortem diagnostic tests exist, and most are limited to the detection of viral antigen by immunofluorescence techniques on tissues or cytologic specimens or high immunoglobulin levels in CSF (cerebrospinal fluid). Diagnosis of CNS distemper is often unreliable due to the relatively low cell count in CSF (<50 cells/μl) and the binding of blocking immunoglobulins in CSF to cell surfaces. A more reliable and definitive test might be possible utilizing direct morphologic detection of the etiologic agent. Distemper is the canine equivalent of human measles, in that both involve a closely related member of the Paramyxoviridae, both produce mucosal inflammation, and may produce CNS complications. In humans, diagnosis of measles-induced subacute sclerosing panencephalitis is through negative stain identification of whole or incomplete viral particles in patient CSF.

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Impairment Questions and Answers

Guides Newsletter ◽

10.1001/amaguidesnewsletters.1999.julaug02 ◽

1999 ◽

Vol 4 (4) ◽

pp. 4-4

Keyword(s):

Symptom Validity ◽

Validity Testing ◽

Symptom Validity Testing ◽

Negative Results ◽

Tunnel Vision ◽

Questions And Answers ◽

Blurry Vision ◽

Fatigue Evaluation ◽

Choice Testing ◽

Rule Out

Abstract Symptom validity testing, also known as forced-choice testing, is a way to assess the validity of sensory and memory deficits, including tactile anesthesias, paresthesias, blindness, color blindness, tunnel vision, blurry vision, and deafness—the common feature of which is a claimed inability to perceive or remember a sensory signal. Symptom validity testing comprises two elements: A specific ability is assessed by presenting a large number of items in a multiple-choice format, and then the examinee's performance is compared with the statistical likelihood of success based on chance alone. Scoring below a norm can be explained in many different ways (eg, fatigue, evaluation anxiety, limited intelligence, and so on), but scoring below the probabilities of chance alone most likely indicates deliberate deception. The positive predictive value of the symptom validity technique likely is quite high because there is no alternative explanation to deliberate distortion when performance is below the probability of chance. The sensitivity of this technique is not likely to be good because, as with a thermometer, positive findings indicate that a problem is present, but negative results do not rule out a problem. Although a compelling conclusion is that the examinee who scores below probabilities is deliberately motivated to perform poorly, malingering must be concluded from the total clinical context.

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