Startseite Medizin Continuous, complete and comparable NT-proBNP reference ranges in healthy children
Artikel
Lizenziert
Nicht lizenziert Erfordert eine Authentifizierung

Continuous, complete and comparable NT-proBNP reference ranges in healthy children

  • Jonas Palm ORCID logo EMAIL logo , Georg Hoffmann , Frank Klawonn , Oktay Tutarel , Herbert Palm , Stefan Holdenrieder und Peter Ewert
Veröffentlicht/Copyright: 18. April 2020
Clinical Chemistry and Laboratory Medicine (CCLM)
Aus der Zeitschrift Clinical Chemistry and Laboratory Medicine (CCLM) Band 58 Heft 9

Abstract

Background

NT-proBNP is one of the most important biomarkers for the diagnosis and risk assessment of heart failure in adults. Age- and gender-independent reference intervals (RIs) have been reported. In contrast, RIs in children are strongly age-dependent, do not exist for all ages and reveal a right-skewed distribution. Accordingly, no common Z-score can be formed and a cross-age interpretive method, so far, is missing.

Methods

Within the paper on hand, new evaluation techniques are applied to already published NT-proBNP study results and additionally to newly gained data. Upper limits (ULs), lower limits (LLs) and 50th percentiles are tested for power-like behavior as a function of age using linear regression analysis. Functions for continuous RIs are derived and reference limits are calculated on a per day basis. A corresponding Zlog formula is deduced and its usefulness is stated in two clinical examples.

Results

The power-like behavior of NT-proBNP concentration from birth to 18 years is demonstrated. With age in days t and measured NT-proBNP value x in pg/mL, an age-specific Zlog value may directly be calculated using the equation:

ZlogNT-proBNP=log x+0.512⋅log t−3.4171.489+0.014⋅log t⋅3.92

Conclusions

Using formulas for UL and LL, continuous RIs from 0 to 18 years may be obtained. Continuity corresponds to physiological changes in the body much better than discrete RIs. With the advent of an NT-proBNP-specific Zlog value, a cross-age Z-score equivalent is providing an easy interpretation aid in everyday pediatric practice. This new approach allows to identify clinical worsening much better, sooner and more clearly than previous absolute values.

Keywords: age-dependent; children; clinical chemistry; NT-proBNP; pediatric cardiology; reference values; zlog value

Acknowledgments

We would like to thank everyone who contributed to this study, in particular, Ms. Laura Wiegand for performing the database query.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interest: All authors have no conflict of interest to declare. The funding organization 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.

References

1. Clerico A, Passino C, Franzini M, Emdin M. Cardiac biomarker testing in the clinical laboratory: where do we stand? General overview of the methodology with special emphasis on natriuretic peptides. Clin Chim Acta 2015;443:17–24.10.1016/j.cca.2014.06.003Suche in Google Scholar PubMed

2. Cantinotti M, Walters HL, Crocetti M, Marotta M, Murzi B, Clerico A. BNP in children with congenital cardiac disease: is there now sufficient evidence for its routine use? Cardiol Young 2015;25:424–37.10.1017/S1047951114002133Suche in Google Scholar PubMed

3. McCullough PA, Kluger AY. Interpreting the wide range of NT-proBNP concentrations in clinical decision making. J Am Coll Cardiol 2018;71:1201–3.10.1016/j.jacc.2018.01.056Suche in Google Scholar PubMed

4. Nir A, Lindinger A, Rauh M, Bar-Oz B, Laer S, Schwachtgen L, et al. NT-pro-B-type natriuretic peptide in infants and children: reference values based on combined data from four studies. Pediatr Cardiol 2009;30:3–8.10.1007/s00246-008-9258-4Suche in Google Scholar PubMed

5. Hoffmann G, Klawonn F, Lichtinghagen R, Orth M. The zlog value as a basis for the standardization of laboratory results. LaboratoriumsMedizin 2017;41:23–32.10.1515/labmed-2017-0135Suche in Google Scholar

6. Schwachtgen L, Herrmann M, Georg T, Schwarz P, Marx N, Lindinger A. Reference values of NT-proBNP serum concentrations in the umbilical cord blood and in healthy neonates and children. Z Kardiol 2005;94:399–404.10.1007/s00392-005-0246-xSuche in Google Scholar PubMed

7. Martinez-Millana A, Hulst JM, Boon M, Witters P, Fernandez-Llatas C, Asseiceira I, et al. Optimisation of children z-score calculation based on new statistical techniques. PLoS One 2018;13:e0208362.10.1371/journal.pone.0208362Suche in Google Scholar PubMed PubMed Central

8. DeVore GR. Computing the Z score and centiles for cross-sectional analysis: a practical approach. J Ultrasound Med 2017;36:459–73.10.7863/ultra.16.03025Suche in Google Scholar PubMed

9. Mir TS, Laux R, Hellwege HH, Liedke B, Heinze C, von Buelow H, et al. Plasma concentrations of aminoterminal pro atrial natriuretic peptide and aminoterminal pro brain natriuretic peptide in healthy neonates: marked and rapid increase after birth. Pediatrics 2003;112:896–9.10.1542/peds.112.4.896Suche in Google Scholar PubMed

10. Albers S, Mir TS, Haddad M, Läer S. N-Terminal pro-brain natriuretic peptide: normal ranges in the pediatric population including method comparison and interlaboratory variability. Clin Chem Lab Med 2006;44:80–5.10.1515/CCLM.2006.016Suche in Google Scholar PubMed

11. Nir A, Bar-Oz B, Perles Z, Brooks R, Korach A, Rein A. N-terminal pro-B-type natriuretic peptide: reference plasma levels from birth to adolescence. Elevated levels at birth and in infants and children with heart diseases. Acta Paediatr 2004;93:603–7.10.1111/j.1651-2227.2004.tb02984.xSuche in Google Scholar

12. Holmgren D, Westerlind A, Lundberg PA, Wåhlander H. Increased plasma levels of natriuretic peptide type B and A in children with congenital heart defects with left compared with right ventricular volume overload or pressure overload. Clin Physiol Funct Imaging 2005;25:263–9.10.1111/j.1475-097X.2005.00622.xSuche in Google Scholar

13. Guignard J, Torrado A, Da Cunha O, Gautier E. Glomerular filtration rate in the first three weeks of life. J Pediatr 1975;87: 268–72.10.1016/S0022-3476(75)80600-7Suche in Google Scholar

14. Otukesh H, Hoseini R, Rahimzadeh N, Hosseini S. Glomerular function in neonates. Iran J Kidney Dis 2012;6:166–72.Suche in Google Scholar

15. Rauh M, Koch A. Plasma N-terminal pro-B-type natriuretic peptide concentrations in a control population of infants and children. Clinical Chem 2003;49:1563–4.10.1373/49.9.1563Suche in Google Scholar PubMed

16. Prontera C, Zucchelli GC, Vittorini S, Storti S, Emdin M, Clerico A. Comparison between analytical performances of polyclonal and monoclonal electrochemiluminescence immunoassays for NT-proBNP. Clin Chim Acta 2009;400:70–3.10.1016/j.cca.2008.10.011Suche in Google Scholar PubMed

17. Asgari S, Higgins V, McCudden C, Adeli K. Continuous reference intervals for 38 biochemical markers in healthy children and adolescents: comparisons to traditionally partitioned reference intervals. Clin Biochem 2019;73:82–9.10.1016/j.clinbiochem.2019.08.010Suche in Google Scholar PubMed

18. Zierk J, Arzideh F, Haeckel R, Cario H, Frühwald MC, Groß HJ, et al. Pediatric reference intervals for alkaline phosphatase. Clin Chem Lab Med 2017;55:102–10.10.1515/cclm-2016-0318Suche in Google Scholar PubMed

Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2019-1185).

Received: 2019-11-16
Accepted: 2020-03-08
Published Online: 2020-04-18
Published in Print: 2020-08-27

©2020 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Editorial
  3. Measurement uncertainty: light in the shadows
  4. Review
  5. Childhood obesity: an overview of laboratory medicine, exercise and microbiome
  6. Mini review
  7. The utility of measurement uncertainty in medical laboratories
  8. Opinion Paper
  9. Do genetic polymorphisms in angiotensin converting enzyme 2 (ACE2) gene play a role in coronavirus disease 2019 (COVID-19)?
  10. Opinion Papers
  11. The current status and future prospects of precision medicine
  12. Precision medicine in medical oncology: hope, disappointment and reality
  13. IFCC Papers
  14. Laboratory practices to mitigate biohazard risks during the COVID-19 outbreak: an IFCC global survey
  15. Operational considerations and challenges of biochemistry laboratories during the COVID-19 outbreak: an IFCC global survey
  16. Genetics and Molecular Diagnostics
  17. Diverse fragment lengths dismiss size selection for serum cell-free DNA: a comparative study of serum and plasma samples
  18. General Clinical Chemistry and Laboratory Medicine
  19. Quantification of plasma remdesivir and its metabolite GS-441524 using liquid chromatography coupled to tandem mass spectrometry. Application to a Covid-19 treated patient
  20. Isotope dilution-LC-MS/MS method for quantification of the urinary cotinine-to-creatinine ratio
  21. A liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based assay to profile 20 plasma steroids in endocrine disorders
  22. Assessment of antinuclear antibodies by indirect immunofluorescence assay: report from a survey by the American Association of Medical Laboratory Immunologists
  23. Evaluation of a novel extended automated particle-based multi-analyte assay for the detection of autoantibodies in the diagnosis of primary biliary cholangitis
  24. Reference Values and Biological Variations
  25. Continuous, complete and comparable NT-proBNP reference ranges in healthy children
  26. Reference-mean-centered statistical quality control
  27. Hematology and Coagulation
  28. Top-down and bottom-up approaches for the estimation of measurement uncertainty in coagulation assays
  29. Cancer Diagnostics
  30. Tumor-associated exosomal miRNA biomarkers to differentiate metastatic vs. nonmetastatic non-small cell lung cancer
  31. Analysis of EGFR mutation status in malignant pleural effusion and plasma from patients with advanced lung adenocarcinoma
  32. Cardiovascular Diseases
  33. Establishing the 99th percentile of a novel assay for high-sensitivity troponin I in a healthy blood donor population
  34. The clinically effective use of cardiac markers by restructuring laboratory profiles at Cardiology wards
  35. Infectious Diseases
  36. Lower nasopharyngeal viral load during the latest phase of COVID-19 pandemic in a Northern Italy University Hospital
  37. SARS-CoV-2 RNA identification in nasopharyngeal swabs: issues in pre-analytics
  38. Rapid identification of SARS-CoV-2-infected patients at the emergency department using routine testing
  39. Evaluation of eleven rapid tests for detection of antibodies against SARS-CoV-2
  40. Development and multicenter performance evaluation of fully automated SARS-CoV-2 IgM and IgG immunoassays
  41. Letters to the Editor
  42. Evaluation of seven commercial SARS-CoV-2 RNA detection kits based on real-time polymerase chain reaction (PCR) in China
  43. Blood sampling after COVID-19 − How to organize large scale phlebotomy services in the post SARS CoV-2 era
  44. Diagnostic performance of a SARS-CoV-2 IgG/IgM lateral flow immunochromatography assay in symptomatic patients presenting to the emergency department
  45. Urinalysis parameters for predicting severity in coronavirus disease 2019 (COVID-19)
  46. Neutrophil-to-lymphocyte ratio predicts the clearance of SARS-CoV-2 RNA in mild COVID-19 patients – a retrospective analysis from Dongxihu Fangcang Hospital in Wuhan, China
  47. Low levels of total and ionized calcium in blood of COVID-19 patients
  48. Is “light cannabis” really light? Determination of cannabinoids content in commercial products
  49. Amino-terminal proB-type natriuretic peptide reference values in umbilical cord blood
  50. The new era of LED microscopes in immunofluorescence anti-nuclear antibody (ANA) testing
  51. The centrifuge brake impacts neither routine coagulation assays nor platelet count in platelet-poor plasma
https://doi.org/10.1515/cclm-2019-1185
Schlagwörter für diesen Artikel
age-dependent; children; clinical chemistry; NT-proBNP; pediatric cardiology; reference values; zlog value

Artikel in diesem Heft

  1. Frontmatter
  2. Editorial
  3. Measurement uncertainty: light in the shadows
  4. Review
  5. Childhood obesity: an overview of laboratory medicine, exercise and microbiome
  6. Mini review
  7. The utility of measurement uncertainty in medical laboratories
  8. Opinion Paper
  9. Do genetic polymorphisms in angiotensin converting enzyme 2 (ACE2) gene play a role in coronavirus disease 2019 (COVID-19)?
  10. Opinion Papers
  11. The current status and future prospects of precision medicine
  12. Precision medicine in medical oncology: hope, disappointment and reality
  13. IFCC Papers
  14. Laboratory practices to mitigate biohazard risks during the COVID-19 outbreak: an IFCC global survey
  15. Operational considerations and challenges of biochemistry laboratories during the COVID-19 outbreak: an IFCC global survey
  16. Genetics and Molecular Diagnostics
  17. Diverse fragment lengths dismiss size selection for serum cell-free DNA: a comparative study of serum and plasma samples
  18. General Clinical Chemistry and Laboratory Medicine
  19. Quantification of plasma remdesivir and its metabolite GS-441524 using liquid chromatography coupled to tandem mass spectrometry. Application to a Covid-19 treated patient
  20. Isotope dilution-LC-MS/MS method for quantification of the urinary cotinine-to-creatinine ratio
  21. A liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based assay to profile 20 plasma steroids in endocrine disorders
  22. Assessment of antinuclear antibodies by indirect immunofluorescence assay: report from a survey by the American Association of Medical Laboratory Immunologists
  23. Evaluation of a novel extended automated particle-based multi-analyte assay for the detection of autoantibodies in the diagnosis of primary biliary cholangitis
  24. Reference Values and Biological Variations
  25. Continuous, complete and comparable NT-proBNP reference ranges in healthy children
  26. Reference-mean-centered statistical quality control
  27. Hematology and Coagulation
  28. Top-down and bottom-up approaches for the estimation of measurement uncertainty in coagulation assays
  29. Cancer Diagnostics
  30. Tumor-associated exosomal miRNA biomarkers to differentiate metastatic vs. nonmetastatic non-small cell lung cancer
  31. Analysis of EGFR mutation status in malignant pleural effusion and plasma from patients with advanced lung adenocarcinoma
  32. Cardiovascular Diseases
  33. Establishing the 99th percentile of a novel assay for high-sensitivity troponin I in a healthy blood donor population
  34. The clinically effective use of cardiac markers by restructuring laboratory profiles at Cardiology wards
  35. Infectious Diseases
  36. Lower nasopharyngeal viral load during the latest phase of COVID-19 pandemic in a Northern Italy University Hospital
  37. SARS-CoV-2 RNA identification in nasopharyngeal swabs: issues in pre-analytics
  38. Rapid identification of SARS-CoV-2-infected patients at the emergency department using routine testing
  39. Evaluation of eleven rapid tests for detection of antibodies against SARS-CoV-2
  40. Development and multicenter performance evaluation of fully automated SARS-CoV-2 IgM and IgG immunoassays
  41. Letters to the Editor
  42. Evaluation of seven commercial SARS-CoV-2 RNA detection kits based on real-time polymerase chain reaction (PCR) in China
  43. Blood sampling after COVID-19 − How to organize large scale phlebotomy services in the post SARS CoV-2 era
  44. Diagnostic performance of a SARS-CoV-2 IgG/IgM lateral flow immunochromatography assay in symptomatic patients presenting to the emergency department
  45. Urinalysis parameters for predicting severity in coronavirus disease 2019 (COVID-19)
  46. Neutrophil-to-lymphocyte ratio predicts the clearance of SARS-CoV-2 RNA in mild COVID-19 patients – a retrospective analysis from Dongxihu Fangcang Hospital in Wuhan, China
  47. Low levels of total and ionized calcium in blood of COVID-19 patients
  48. Is “light cannabis” really light? Determination of cannabinoids content in commercial products
  49. Amino-terminal proB-type natriuretic peptide reference values in umbilical cord blood
  50. The new era of LED microscopes in immunofluorescence anti-nuclear antibody (ANA) testing
  51. The centrifuge brake impacts neither routine coagulation assays nor platelet count in platelet-poor plasma
Jetzt anmelden und 20% sparen
Institutioneller Zugang
Wie funktioniert Authentifizierung?
Haben Sie eine Idee, wie wir unsere Website verbessern können?
Bitte schreiben Sie uns.
© 2025 De Gruyter Brill
Heruntergeladen am 12.12.2025 von https://www.degruyterbrill.com/document/doi/10.1515/cclm-2019-1185/html?lang=de
Button zum nach oben scrollen