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

  • Paula Lafuente-Ganuza , Paloma Lequerica-Fernandez , Francisco Carretero , Ana I. Escudero , Eduardo Martinez-Morillo , Enric Sabria , Ignacio Herraiz , Alberto Galindo , Ana Lopez , Maria L. Martinez-Triguero and Francisco V. Alvarez EMAIL logo
Published/Copyright: November 16, 2019
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 58 Issue 3

Abstract

Background

The 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.

Methods

A 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.

Results

For 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.

Conclusions

An 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.

Keywords: NT-proBNP; placental growth factor (PlGF); pre-eclampsia; soluble FMS-like tyrosine kinase 1 (sFlt-1)

Acknowledgments

The authors greatly appreciate all of the collaborators from different hospitals as well as the Catedra de Inteligencia Analitica, Universidad de Oviedo, Oviedo, Spain.

  1. Author contributions: P. Lafuente, P. Lequerica, and E. Martinez: statistical analysis and clinical characteristics of the patients; A. Galindo, I. Herraiz, A. Escudero, M. Martinez and E. Lopez: provision of study material or patients; F. Carretero: statistical analysis using machine learning; F.V. Alvarez: conceived and designed the study. All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: I. Herraiz and A. Galindo have received lecture fees and consultancy payments from Roche Diagnostics. The rest of the authors report no conflict of interest.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2019-0939).

Received: 2019-09-05
Accepted: 2019-10-12
Published Online: 2019-11-16
Published in Print: 2020-02-25

©2020 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2019-0939
Keywords for this article
NT-proBNP; placental growth factor (PlGF); pre-eclampsia; soluble FMS-like tyrosine kinase 1 (sFlt-1)

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Progress in understanding the use of human chorionic gonadotropin as a tumor marker
  4. Reviews
  5. Biomarkers for prostate cancer: prostate-specific antigen and beyond
  6. Gut microbiome investigation in celiac disease: from methods to its pathogenetic role
  7. Opinion Papers
  8. Understanding and managing interferences in clinical laboratory assays: the role of laboratory professionals
  9. A step forward in identifying the right human chorionic gonadotropin assay for testicular cancer
  10. EFLM Opinion Paper
  11. Validation and verification of examination procedures in medical laboratories: opinion of the EFLM Working Group Accreditation and ISO/CEN standards (WG-A/ISO) on dealing with ISO 15189:2012 demands for method verification and validation
  12. Guidelines and Recommendations
  13. An updated protocol based on CLSI document C37 for preparation of off-the-clot serum from individual units for use alone or to prepare commutable pooled serum reference materials
  14. General Clinical Chemistry and Laboratory Medicine
  15. Highly accurate and explainable detection of specimen mix-up using a machine learning model
  16. Impact of delta check time intervals on error detection capability
  17. Effect of long-term frozen storage and thawing of stool samples on faecal haemoglobin concentration and diagnostic performance of faecal immunochemical tests
  18. A more accurate prediction to rule in and rule out pre-eclampsia using the sFlt-1/PlGF ratio and NT-proBNP as biomarkers
  19. Macro vitamin B12: an underestimated threat
  20. Evaluation of the primary biliary cholangitis-related serologic profile in a large cohort of Belgian systemic sclerosis patients
  21. High frequency of anti-parietal cell antibody (APCA) and intrinsic factor blocking antibody (IFBA) in individuals with severe vitamin B12 deficiency – an observational study in primary care patients
  22. DOAC-Remove abolishes the effect of direct oral anticoagulants on activated protein C resistance testing in real-life venous thromboembolism patients
  23. Cancer Diagnostics
  24. How comparable are total human chorionic gonadotropin (hCGt) tumour markers assays?
  25. Diabetes
  26. Measurement accuracy of two professional-use systems for point-of-care testing of blood glucose
  27. Letters to the Editor
  28. Human chorionic gonadotropin in oncology: a matter of tight (bio)marking
  29. More robust analytical evidence should support the selection of human chorionic gonadotropin assays for oncology application
  30. Letter in reply to the letter to the editor of Ferraro S and Panteghini M with the title “More robust analytical evidence should support the selection for human chorionic gonadotropin assays for oncology application”
  31. Definition of analytical quality specifications for serum total folate measurements using a simulation outcome-based model
  32. Alarmed by misleading interference in free T3 and free T4 assays: a new case of anti-streptavidin antibodies
  33. A root cause analysis of ‘falsely elevated’ oxygen saturation: investigation of pneumatic tube transport and differences between estimated and measured saturation in a critical patient population
  34. The chaos of serologic markers in interstitial pneumonia with autoimmune features can be corrected by the laboratory physician
  35. Vitamin A and E gender and age stratification in adults
  36. Detection of monoclonal B-lymphocytosis: interest of cellular population data and CytoDiff™ analysis
  37. Urinary reference intervals for gadolinium in individuals without recent exposure to gadolinium-based contrast agents
  38. Molecular diagnosis of toxoplasmosis: evaluation of automated DNA extraction using eMAG® (bioMérieux) on buffy coat, cerebrospinal and bronchoalveolar lavage fluids
  39. Retraction
  40. Retraction of: The Effect of a Gender Difference in the Apolipoprotein E Gene DNA Polymorphism on Serum Lipid Levels in a Serbian Healthy Population
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