Related Experiment Video
Updated: Dec 23, 2025
How to Administer Near-Infrared Spectroscopy in Critically ill Neonates, Infants, and Children
Published on: August 19, 2020
Continuous, complete and comparable NT-proBNP reference ranges in healthy children
Jonas Palm1, Georg Hoffmann2, Frank Klawonn3,4
1Department of Congenital Heart Disease and Paediatric Cardiology, German Heart Centre Munich, Technical University of Munich, Lazarettstraße 36, D-80636 Munich, Germany.
Insights
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.
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.
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${\rm{Zlo}}{{\rm{g}}_{{\rm{NT - proBNP}}}} = {{\log \;x + 0.512 \cdot \log \;t - 3.417} \over {1.489 + 0.014 \cdot \log \;t}} \cdot 3.92$.
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.
