A more accurate prediction to rule in and rule out pre-eclampsia using the sFlt-1/PlGF ratio and NT-proBNP as biomarkers

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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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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Gestational week-specific of uterine artery Doppler indices in predicting preeclampsia: a hospital-based retrospective cohort study

BMC Pregnancy and Childbirth ◽

10.1186/s12884-021-04329-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Jiang-Nan Wu ◽

Ming-Qing Li ◽

Feng Xie ◽

Bin Zhang

Keyword(s):

Cohort Study ◽

Retrospective Cohort Study ◽

Predictive Value ◽

Early Onset ◽

Retrospective Cohort ◽

Uterine Artery ◽

Youden Index ◽

Gestational Week ◽

Doppler Indices ◽

The Right

Abstract Background Plenty of studies explored the relationship between uterine artery (UtA) Doppler indices and the onset of preeclampsia at different trimesters. However, few studies test the gestational week-specific predictive value of the UtA indices for subsequent preeclampsia and compare the difference of right or left UtA indices (e.g., pulsatility or resistance index [PI or RI]). Methods Hospital-based retrospective cohort study of singleton pregnant women who received the Doppler test between 2012 and 2016 was conducted in 2018. The predictive performance of the UtA indices for preeclampsia and its variants, including early-onset preeclampsia (< 34 weeks) and preterm preeclampsia (< 37 weeks), was estimated. Results The UtA indices, with a cutoff value of 1.11 for the right and left UtA-PI, and 0.66 and 0.63 for the right and left UtA-RI, respectively, were effective predictors for subsequent preeclampsia. The prediction was satisfactory at the 9th week of the Doppler scan: areas under the curve ≥ 0.80, the Youden index ranging from 0.54 to 0.58, the sensitivity of 63.2 ~ 73.7%, and the specificity 84.2 ~ 91.3%, respectively. The UtA indices had comparable performance in screening for early-onset and preterm preeclampsia but showed lower predictive value for late-onset cases. Among these indices, the right UtA-RI had the highest specificity (all P < 0.01), while the left UtA-PI showed good authenticity (higher Youden index) in predicting the disorder. Conclusions The second-trimester measured UtA indices had a satisfactory performance at the 9th week in predicting subsequent preeclampsia. The right UtA-RI was the first choice in ruling out preeclampsia, while the left UtA-PI showed the best authenticity of the prediction.

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The predictive value of sequential cervical length screening in singleton pregnancies after cerclage: a retrospective cohort study

BMC Pregnancy and Childbirth ◽

10.1186/s12884-016-0866-3 ◽

2016 ◽

Vol 16 (1) ◽

Cited By ~ 7

Author(s):

Sophie Pils ◽

Wolfgang Eppel ◽

Regina Promberger ◽

Max-Paul Winter ◽

Rudolf Seemann ◽

...

Keyword(s):

Cohort Study ◽

Retrospective Cohort Study ◽

Predictive Value ◽

Retrospective Cohort ◽

Cervical Length ◽

Singleton Pregnancies

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Two-Hour Algorithm for Rapid Triage of Suspected Acute Myocardial Infarction Using a High-Sensitivity Cardiac Troponin I Assay

Clinical Chemistry ◽

10.1373/clinchem.2019.305193 ◽

2019 ◽

Vol 65 (11) ◽

pp. 1437-1447 ◽

Cited By ~ 9

Author(s):

Thomas Nestelberger ◽

Jasper Boeddinghaus ◽

Jaimi Greenslade ◽

William A Parsonage ◽

Martin Than ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Predictive Value ◽

Cardiac Troponin ◽

Troponin I ◽

Validation Cohort ◽

High Sensitivity ◽

Final Diagnosis ◽

Derivation Cohort ◽

Rule Out

Abstract BACKGROUND We aimed to derive and externally validate a 0/2-h algorithm using the high-sensitivity cardiac troponin I (hs-cTnI)-Access assay. METHODS We enrolled patients presenting to the emergency department with symptoms suggestive of acute myocardial infarction (AMI) in 2 prospective diagnostic studies using central adjudication. Two independent cardiologists adjudicated the final diagnosis, including all available medical information including cardiac imaging. hs-cTnI-Access concentrations were measured at presentation and after 2 h in a blinded fashion. RESULTS AMI was the adjudicated final diagnosis in 164 of 1131 (14.5%) patients in the derivation cohort. Rule-out by the hs-cTnI-Access 0/2-h algorithm was defined as 0-h hs-cTnI-Access concentration <4 ng/L in patients with an onset of chest pain >3 h (direct rule-out) or a 0-h hs-cTnI-Access concentration <5 ng/L and an absolute change within 2 h <5 ng/L in all other patients. Derived thresholds for rule-in were a 0-h hs-cTnI-Access concentration ≥50 ng/L (direct rule-in) or an absolute change within 2 h ≥20 ng/L. In the derivation cohort, these cutoffs ruled out 55% of patients with a negative predictive value (NPV) of 99.8% (95% CI, 99.3–100) and sensitivity of 99.4% (95% CI, 96.5–99.9), and ruled in 30% of patients with a positive predictive value (PPV) of 73% (95% CI, 66.1–79). In the validation cohort, AMI was the adjudicated final diagnosis in 88 of 1280 (6.9%) patients. These cutoffs ruled out 77.9% of patients with an NPV of 99.8% (95% CI, 99.3–100) and sensitivity of 97.7% (95% CI, 92.0–99.7), and ruled in 5.8% of patients with a PPV of 77% (95% CI, 65.8–86) in the validation cohort. CONCLUSIONS Safety and efficacy of the l hs-cTnI-Access 0/2-h algorithm for triage toward rule-out or rule-in of AMI are very high. TRIAL REGISTRATION APACE, NCT00470587; ADAPT, ACTRN1261100106994; IMPACT, ACTRN12611000206921.

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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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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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P2675Validation of a 0/1h diagnostic algorithm using a point of care high-sensitivity troponin I assay

European Heart Journal ◽

10.1093/eurheartj/ehz748.0993 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

N Soerensen ◽

J T Neumann ◽

F Ojeda ◽

E Giannitsis ◽

E Spanuth ◽

...

Keyword(s):

Myocardial Infarction ◽

Predictive Value ◽

Diagnostic Performance ◽

Troponin I ◽

Validation Cohort ◽

Point Of Care ◽

Diagnostic Algorithm ◽

High Sensitivity ◽

High Sensitivity Troponin ◽

Rule Out

Abstract Background The numbers of patients presenting to emergency departments with suspected acute myocardial infarction (AMI) are increasing worldwide. The use of point of care (POC) troponin assays with an increased sensitivity – equal to laboratory-based high-sensitivity immunoassays – might enable faster decision making in this high-risk population. Objective To validate a rapid diagnostic algorithm using a novel point of care (POC) high-sensitivity troponin I (hs-TnI) assay in comparison to a laboratory-based hs-TnI assay. Methods A diagnostic 0/1h algorithm for the POC hs-TnI assay (PATHFAST hs-cTnI, LSI Medience) was derived in a dataset of 669 patients with suspected AMI, aiming for a negative predictive value (NPV) ≥99.5% for rule-out and a positive predictive value (PPV) ≥75% for rule-in of non-ST-elevation myocardial infarction (NSTEMI). The performance of the developed algorithm was tested in a validation cohort of 610 patients. Diagnostic accuracy of the POC hs-TnI assay was compared to an established hs-TnI assay (Abbott ARCHITECT) using an ESC guideline-recommended 0/1h diagnostic algorithm. Results The derived 0/1h algorithm consisted of an admission POC hs-TnI <4 ng/L and a delta from 0h to 1h <3 ng/L for rule-out and an admission POC hs-TnI ≥90 ng/L or a delta from 0h to 1h ≥20 ng/L for rule-in of NSTEMI. Application of the algorithm in the validation cohort showed a NPV of 99.7% (Confidence Interval (CI) 98.1%-100.0%) and 48.0% of patients ruled out, while 14.6% were ruled in with a PPV of 86.5% (CI 77.6%-92.8%). The diagnostic performance of the POC hs-TnI assay was comparable to guideline-recommended use of a laboratory-based hs-TnI assay (Figure 1). Conclusion The clinical application of a 0/1h diagnostic algorithm based on a novel POC hs-TnI assay showed good diagnostic performance and was comparable to a laboratory-based hs-TnI assay. Acknowledgement/Funding German Center of Cardiovascular Research, Abbott Diagnostics, DIAneering GmbH, German Heart Foundation/ German Foundation of Heart Research

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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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