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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 and Peter Ewert
Published/Copyright: April 18, 2020
Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 58 Issue 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.

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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

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https://doi.org/10.1515/cclm-2019-1185
Keywords for this article
age-dependent; children; clinical chemistry; NT-proBNP; pediatric cardiology; reference values; zlog value

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  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
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  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
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  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
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  21. A liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based assay to profile 20 plasma steroids in endocrine disorders
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  23. Evaluation of a novel extended automated particle-based multi-analyte assay for the detection of autoantibodies in the diagnosis of primary biliary cholangitis
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