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

Jonas Palm¹, Georg Hoffmann², Frank Klawonn^3,4

¹Department of Congenital Heart Disease and Paediatric Cardiology, German Heart Centre Munich, Technical University of Munich, Lazarettstraße 36, D-80636 Munich, Germany.

Clinical Chemistry and Laboratory Medicine

|April 20, 2020

Summary

This study introduces a new Zlog formula for NT-proBNP in children, enabling continuous age-specific reference intervals for better heart failure assessment. This biomarker tool aids early clinical worsening detection in pediatric practice.

Keywords:

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

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Area of Science:

Biochemistry
Pediatric Cardiology
Biomarker Research

Background:

N-terminal pro-B-type natriuretic peptide (NT-proBNP) is crucial for adult heart failure diagnosis and risk assessment.
Pediatric NT-proBNP reference intervals (RIs) are age-dependent, lack coverage for all ages, and are right-skewed.
Current pediatric RIs prevent common Z-score formation and cross-age interpretation.

Purpose of the Study:

To develop a novel, age-independent interpretive method for NT-proBNP in children.
To establish continuous reference limits for NT-proBNP across pediatric age groups.
To introduce a Zlog formula for simplified cross-age NT-proBNP interpretation.

Main Methods:

Applied new evaluation techniques to existing and new NT-proBNP data.
Utilized linear regression analysis to assess power-like behavior of NT-proBNP limits with age.
Derived functions for continuous RIs and calculated daily reference limits.
Deduced a Zlog formula for NT-proBNP interpretation.

Main Results:

Demonstrated power-like behavior of NT-proBNP concentration from birth to 18 years.
Established an age-specific Zlog formula for NT-proBNP: ZlogNT-proBNP = (log x + 0.512*log t - 3.417) / (1.489 + 0.014*log t) * 3.92.
Validated the formula's utility with two clinical examples.

Conclusions:

Continuous NT-proBNP RIs from 0 to 18 years can be obtained using derived upper and lower limit formulas.
The NT-proBNP-specific Zlog value serves as a cross-age Z-score equivalent, simplifying pediatric practice.
This approach enhances the identification of clinical worsening, offering earlier and clearer insights than absolute values.