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

Palm J, Hoffmann G, Klawonn F, Tutarel O, Palm H, Holdenrieder S, Ewert P.

Clin Chem Lab Med. 2020 Apr 18. pii: /j/cclm.ahead-of-print/cclm-2019-1185/cclm-2019-1185.xml. doi: 10.1515/cclm-2019-1185. [Epub ahead of print]

PMID: 32305952

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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 ${\rm{Zlo}}{{\rm{g}}_{{\rm{NT – proBNP}}}} = {{\log \;x + 0.512 \cdot \log \;t – 3.417} \over {1.489 + 0.014 \cdot \log \;t}} \cdot 3.92$ 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.

 

source:https://pubmed.ncbi.nlm.nih.gov/32305952/

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