Jump to ContentJump to Main Navigation
Show Summary Details
In This Section

Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter / Tate, Jillian R.

12 Issues per year

IMPACT FACTOR 2016: 3.432

CiteScore 2016: 2.21

SCImago Journal Rank (SJR) 2015: 0.873
Source Normalized Impact per Paper (SNIP) 2015: 0.982

See all formats and pricing
In This Section
Volume 44, Issue 1 (Jan 2006)


N-Terminal pro-brain natriuretic peptide: normal ranges in the pediatric population including method comparison and interlaboratory variability

Stefanie Albers
  • Clinical Pharmacy and Pharmacotherapy, Heinrich-Heine University, Düsseldorf, Germany
/ Thomas S. Mir
  • Department of Pediatric Cardiology, University Hospital Hamburg-Eppendorf, Hamburg, Germany
/ Munif Haddad
  • Department of Clinical Chemistry, University Hospital Hamburg-Eppendorf, Hamburg, Germany
/ Stephanie Läer
  • Clinical Pharmacy and Pharmacotherapy, Heinrich-Heine University, Düsseldorf, Germany
Published Online: 2011-09-21 | DOI: https://doi.org/10.1515/CCLM.2006.016


The aim of the present study was the investigation of N-terminal pro-brain natriuretic peptide (NT-proBNP) in the pediatric population. This is essential for adequate monitoring and classification of pediatric patients with heart disease, but no consistent data are available yet. In addition, the comparability of two commercially available NT-proBNP assays and the inter-laboratory variability for the most suitable one were assessed. For this purpose, 408 subjects (1–29years) were included. NT-proBNP was determined with a non-competitive electrochemiluminescent immunoassay (Roche NT-proBNP; n=402) and a competitive enzyme-immunoassay (Biomedica NT-proBNP; n=402). Inter-laboratory variability was evaluated for the Roche assay by stepwise inclusion of four and 11 centers throughout Germany, respectively. Roche NT-proBNP ranged from 5.0 to 391.5ng/L, with higher values for younger children. The 97.5th (75th) percentile curve ranged from 319.9ng/L (231.2 ng/L, 1–3years) to 114.9ng/L (53.3 ng/L, 18years). In contrast, Biomedica NT-proBNP ranged from 253.7 to 7602.8 ng/L, with no significant age dependency. The mean difference between the assays was 1649.7ng/L (95% confidence interval 1546.3–1753.1ng/L). Inter-laboratory variability ranged from 6.5% to 3.8%, covering a range from 51.3 to 6618.1ng/L. The assay seems to influence the interpretation of resulting NT-proBNP values and therefore has to be chosen carefully. For the monitoring and classification of pediatric patients with congenital heart disease, age-based NT-proBNP values should be used.

Keywords: assay; biological markers; congenital heart defect; pediatrics; pro-brain natriuretic peptide; reference values


  • 1.

    Clerico A, Emdin M. Diagnostic accuracy and prognostic relevance of the measurement of cardiac natriuretic peptides: a review. Clin Chem 2004; 50:33–50.CrossrefGoogle Scholar

  • 2.

    Doust JA, Glasziou PP, Pietrzak E, Dobson AJ. A systematic review of the diagnostic accuracy of natriuretic peptides for heart failure. Arch Intern Med 2004; 164:1978–84.Google Scholar

  • 3.

    Doust JA, Pietrzak E, Dobson A, Glasziou P. How well does B-type natriuretic peptide predict death and cardiac events in patients with heart failure: systematic review. Br Med J 2005; 330:625.Google Scholar

  • 4.

    Troughton RW, Frampton CM, Yandle TG, Espiner EA, Nicholls MG, Richards AM. Treatment of heart failure guided by plasma aminoterminal brain natriuretic peptide (N-BNP) concentrations. Lancet 2000; 355:1126–30.Google Scholar

  • 5.

    Vanderheyden M, Bartunek J, Goethals M. Brain and other natriuretic peptides: molecular aspects. Eur J Heart Fail 2004; 6:261–8.CrossrefGoogle Scholar

  • 6.

    Collinson PO, Barnes SC, Gaze DC, Galasko G, Lahiri A, Senior R. Analytical performance of the N-terminal pro B-type natriuretic peptide (NT-proBNP) assay on the Elecsys 1010 and 2010 analysers. Eur J Heart Fail 2004; 6:365–8.Google Scholar

  • 7.

    Mueller T, Gegenhuber A, Dieplinger B, Poelz W, Haltmayer M. Long-term stability of endogenous B-type natriuretic peptide (BNP) and amino terminal proBNP (NT-proBNP) in frozen plasma samples. Clin Chem Lab Med 2004; 42:942–4.CrossrefGoogle Scholar

  • 8.

    Gobinet-Georges A, Valli N, Filliatre H, Dubernet MF, Dedeystere O, Bordenave L. Stability of brain natriuretic peptide (BNP) in human whole blood and plasma. Clin Chem Lab Med 2000; 38:519–23.Google Scholar

  • 9.

    Hunt PJ, Richards AM, Nicholls MG, Yandle TG, Doughty RN, Espiner EA. Immunoreactive amino-terminal pro-brain natriuretic peptide (NT-PROBNP): a new marker of cardiac impairment. Clin Endocrinol (Oxf) 1997; 47:287–96.CrossrefGoogle Scholar

  • 10.

    Tulevski , II, Groenink M, van Der Wall EE, van Veldhuisen DJ, Boomsma F, Stoker J, et al. Increased brain and atrial natriuretic peptides in patients with chronic right ventricular pressure overload: correlation between plasma neurohormones and right ventricular dysfunction. Heart 2001; 86:27–30.CrossrefGoogle Scholar

  • 11.

    Book WM, Hott BJ, McConnell M. B-type natriuretic peptide levels in adults with congenital heart disease and right ventricular failure. Am J Cardiol 2005; 95:545–6.CrossrefGoogle Scholar

  • 12.

    Bolger AP, Sharma R, Li W, Leenarts M, Kalra PR, Kemp M, et al. Neurohormonal activation and the chronic heart failure syndrome in adults with congenital heart disease. Circulation 2002; 106:92–9.CrossrefGoogle Scholar

  • 13.

    Hopkins WE, Chen Z, Fukagawa NK, Hall C, Knot HJ, LeWinter MM. Increased atrial and brain natriuretic peptides in adults with cyanotic congenital heart disease: enhanced understanding of the relationship between hypoxia and natriuretic peptide secretion. Circulation 2004; 109:2872–7.CrossrefGoogle Scholar

  • 14.

    Wang TJ, Larson MG, Levy D, Benjamin EJ, Leip EP, Omland T, et al. Plasma natriuretic peptide levels and the risk of cardiovascular events and death. N Engl J Med 2004; 350:655–63.Google Scholar

  • 15.

    Raymond I, Groenning BA, Hildebrandt PR, Nilsson JC, Baumann M, Trawinski J, et al. The influence of age, sex and other variables on the plasma level of N-terminal pro brain natriuretic peptide in a large sample of the general population. Heart 2003; 89:745–51.CrossrefGoogle Scholar

  • 16.

    Loke I, Squire IB, Davies JE, Ng LL. Reference ranges for natriuretic peptides for diagnostic use are dependent on age, gender and heart rate. Eur J Heart Fail 2003; 5:599–606.CrossrefGoogle Scholar

  • 17.

    Mir TS, Marohn S, Laer S, Eiselt M, Grollmus O, Weil J. Plasma concentrations of N-terminal pro-brain natriuretic peptide in control children from the neonatal to adolescent period and in children with congestive heart failure. Pediatrics 2002; 110:e76.CrossrefGoogle Scholar

  • 18.

    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.CrossrefGoogle Scholar

  • 19.

    Nir A, Bar-Oz B, Perles Z, Brooks R, Korach A, Rein AJ. 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.CrossrefGoogle Scholar

  • 20.

    Rauh M, Koch A. Plasma N-terminal pro-B-type natriuretic peptide concentrations in a control population of infants and children. Clin Chem 2003; 49:1563–4.CrossrefGoogle Scholar

  • 21.

    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.CrossrefGoogle Scholar

  • 22.

    Clerico A, Del Ry S, Giannessi D. Measurement of cardiac natriuretic hormones (atrial natriuretic peptide, brain natriuretic peptide, and related peptides) in clinical practice: the need for a new generation of immunoassay methods. Clin Chem 2000; 46:1529–34.Google Scholar

  • 23.

    Mueller T, Gegenhuber A, Poelz W, Haltmayer M. Comparison of the Biomedica NT-proBNP enzyme immunoassay and the Roche NT-proBNP chemiluminescence immunoassay: implications for the prediction of symptomatic and asymptomatic structural heart disease. Clin Chem 2003; 49:976–9.CrossrefGoogle Scholar

  • 24.

    Hammerer-Lercher A, Ludwig W, Falkensammer G, Muller S, Neubauer E, Puschendorf B, et al. Natriuretic peptides as markers of mild forms of left ventricular dysfunction: effects of assays on diagnostic performance of markers. Clin Chem 2004; 50:1174–83.CrossrefGoogle Scholar

  • 25.

    Sokoll LJ, Baum H, Collinson PO, Gurr E, Haass M, Luthe H, et al. Multicenter analytical performance evaluation of the Elecsys proBNP assay. Clin Chem Lab Med 2004; 42:965–72.CrossrefGoogle Scholar

  • 26.

    Mir TS, Flato M, Falkenberg J, Haddad M, Budden R, Weil J, et al. Plasma concentrations of N-terminal brain natriuretic peptide in healthy children, adolescents, and young adults: effect of age and gender. Pediatr Cardiol 2005. In press. (DOI: 10.1007/s00246-005-1022-4).CrossrefGoogle Scholar

  • 27.

    Biomedica Group. Assay specification, 2004.Google Scholar

  • 28.

    Roche Diagnostics. Assay specifications, 2002.Google Scholar

  • 29.

    Bland JM, Altman DG. Measuring agreement in method comparison studies. Stat Methods Med Res 1999; 8:135–60.CrossrefGoogle Scholar

  • 30.

    Koch A, Singer H. Normal values of B type natriuretic peptide in infants, children, and adolescents. Heart 2003; 89:875–8.CrossrefGoogle Scholar

  • 31.

    Hall C. Essential biochemistry and physiology of (NT-pro)BNP. Eur J Heart Fail 2004; 6:257–60.CrossrefGoogle Scholar

  • 32.

    Shih HC, Chao L, Chao J. Age and hormonal dependence of tonin levels in rat submandibular gland as determined by a new direct radioimmunoassay. Biochem J 1986; 238:145–9.Google Scholar

  • 33.

    Maffei S, Del Ry S, Prontera C, Clerico A. Increase in circulating levels of cardiac natriuretic peptides after hormone replacement therapy in postmenopausal women. Clin Sci (Lond) 2001; 101:447–53.CrossrefGoogle Scholar

About the article

Corresponding author. Stephanie Läer, MD, PhD, Clinical Pharmacy and Pharmacotherapy, Heinrich-Heine University of Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany Phone: +49-211-8113664, Fax: +49-211-8113847,

Received: 2005-08-10

Accepted: 2005-10-07

Published Online: 2011-09-21

Published in Print: 2006-01-01

Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/CCLM.2006.016.

Export Citation

©2006 by Walter de Gruyter Berlin New York. Copyright Clearance Center

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

Chiara Caselli, Rosetta Ragusa, Concetta Prontera, Manuela Cabiati, Massimiliano Cantinotti, Giovanni Federico, Silvia Del Ry, Maria Giovanna Trivella, and Aldo Clerico
Biomarkers in Medicine, 2016
Melanie K. Nies, David D. Ivy, and Allen D. Everett
PROTEOMICS - Clinical Applications, 2014, Volume 8, Number 11-12, Page 862
Corinna Binder-Heschl, Berndt Urlesberger, Martin Koestenberger, Bernhard Schwaberger, Georg M. Schmölzer, and Gerhard Pichler
Acta Paediatrica, 2015, Volume 104, Number 1, Page 32
Sibo Tian, Kim M. Hirshfield, Salma K. Jabbour, Deborah Toppmeyer, Bruce G. Haffty, Atif J. Khan, and Sharad Goyal
Frontiers in Oncology, 2014, Volume 4
Hyun Kyung Bae, Do Kyung Lee, Jung Hyun Kwon, Hae Soon Kim, Sejung Sohn, and Young Mi Hong
Korean Journal of Pediatrics, 2014, Volume 57, Number 8, Page 357
Nura Afshani, Simone Schülein, Bruce M. Biccard, Jenny M. Thomas, and Greg Hammer
Pediatric Anesthesia, 2015, Volume 25, Number 2, Page 115
Nagib Dahdah and Anne Fournier
Diagnostics, 2013, Volume 3, Number 1, Page 1
Massimiliano Cantinotti, Yuk Law, Simona Vittorini, Maura Crocetti, Marotta Marco, Bruno Murzi, and Aldo Clerico
Heart Failure Reviews, 2014, Volume 19, Number 6, Page 727
Pinar Bambul Heck, Jan Müller, Ruth Weber, and Alfred Hager
European Journal of Heart Failure, 2013, Volume 15, Number 6, Page 644
A. M. C. Mavinkurve-Groothuis, K. A. Marcus, M. Pourier, J. Loonen, T. Feuth, P. M. Hoogerbrugge, C. L. de Korte, and L. Kapusta
European Heart Journal - Cardiovascular Imaging, 2013, Volume 14, Number 6, Page 562
Antonio Ruggiero, Gabriella De Rosa, Daniela Rizzo, Andrea Leo, Palma Maurizi, Alessia De Nisco, Francesca Vendittelli, Cecilia Zuppi, Alvaro Mordente, and Riccardo Riccardi
International Journal of Clinical Oncology, 2013, Volume 18, Number 5, Page 927
Joseph M. Collaco, Lewis H. Romer, Bridget D. Stuart, John D. Coulson, Allen D. Everett, Edward E. Lawson, Joel I. Brenner, Anna T. Brown, Melanie K. Nies, Priya Sekar, Lawrence M. Nogee, and Sharon A. McGrath-Morrow
Pediatric Pulmonology, 2012, Volume 47, Number 11, Page 1042
Ariane McNeal-Davidson, Anne Fournier, Linda Spigelblatt, Claire Saint-Cyr, Thomas S Mir, Amiram Nir, Frédéric Dallaire, Jocelyne Cousineau, Edgard Delvin, and Nagib Dahdah
Pediatrics International, 2012, Volume 54, Number 5, Page 627
Martin Christopher Johns and Carol Stephenson
The American Journal of Cardiology, 2008, Volume 101, Number 3, Page S76
Angelika Hammerer-Lercher, Bernd Puschendorf, and Johannes Mair
Jugoslovenska medicinska biohemija, 2006, Volume 25, Number 4, Page 287
Pierluigi Politi, Piercarlo Minoretti, Noemi Piaggi, Natascia Brondino, and Enzo Emanuele
Neuroscience Letters, 2007, Volume 417, Number 3, Page 322
Kazunari Kaneko, Ken Yoshimura, Atsushi Ohashi, Takahisa Kimata, Tomohiko Shimo, and Shoji Tsuji
Pediatric Cardiology, 2011, Volume 32, Number 8, Page 1106
Annelies M.C. Mavinkurve-Groothuis, Jacqueline Groot-Loonen, Karen A. Marcus, Louise Bellersen, Ton Feuth, Jos P.M. Bökkerink, Peter M. Hoogerbrugge, Chris de Korte, and Livia Kapusta
Ultrasound in Medicine & Biology, 2010, Volume 36, Number 11, Page 1783
Tanja M. Raedle-Hurst, Karsten Koenigstein, Frank Gruenhage, Jochen Raedle, Eva Herrmann, and Hashim Abdul-Khaliq
American Heart Journal, 2010, Volume 160, Number 6, Page 1105
Daphne T. Hsu and Charles E. Canter
Heart Failure Clinics, 2010, Volume 6, Number 4, Page 415
Daniëlle Robbers-Visser, Livia Kapusta, Lennie van Osch-Gevers, Jan L.M. Strengers, Eric Boersma, Yolanda B. de Rijke, Frans Boomsma, Ad J.J.C. Bogers, and Willem A. Helbing
The Journal of Thoracic and Cardiovascular Surgery, 2009, Volume 138, Number 1, Page 89
Markus Rauchenzauner, Edda Haberlandt, Carla Rösslhuber, Gerhard Luef, Markus Otto, Angelika Hammerer-Lercher, Andrea Griesmacher, and Kevin Rostasy
Epilepsy Research, 2009, Volume 86, Number 2-3, Page 131
Roberto F. Machado, Mariana Hildesheim, Laurel Mendelsohn, Alan T. Remaley, Gregory J. Kato, and Mark T. Gladwin
British Journal of Haematology, 2011, Volume 154, Number 4, Page 512
Christopher Ratnasamy, Daniel D. Kinnamon, Steven E. Lipshultz, and Paolo Rusconi
American Heart Journal, 2008, Volume 155, Number 3, Page 527
Massimiliano Cantinotti, Stefania Giovannini, Bruno Murzi, and Aldo Clerico
Clinical Chemistry and Laboratory Medicine, 2011, Volume 49, Number 4
Angelika Hammerer-Lercher, Andrea Griesmacher, Gerhard Pölzl, Natascha Brinskelle-Schmal, Johannes Mair, Matthias Frick, and Gerhard Hawa
Clinical Chemistry and Laboratory Medicine, 2009, Volume 47, Number 10
Angelika Hammerer-Lercher, Bernd Puschendorf, and Johannes Mair
Jugoslovenska medicinska biohemija, 2006, Volume 25, Number 4, Page 287
Silvia Favilli, Stefano Frenos, Donatella Lasagni, Filippo Frenos, Iva Pollini, Gabriella Bernini, Maurizio Aricò, and Roberta M Bini
Journal of Cardiovascular Medicine, 2009, Volume 10, Number 4, Page 298
Julie Smith, Jens P. Goetze, Claus B. Andersen, and Niels Vejlstrup
Cardiology in the Young, 2010, Volume 20, Number 04, Page 353
Nagib Dahdah, Ana Siles, Anne Fournier, Jocelyne Cousineau, Edgard Delvin, Claire Saint-Cyr, Linda Spiegelblatt, Yvette Bonny, Michèle Vartian, and Martine Montigny
Pediatric Cardiology, 2009, Volume 30, Number 6, Page 810
Annelies M.C. Mavinkurve-Groothuis, Jacqueline Groot-Loonen, Louise Bellersen, Milanthy S. Pourier, Ton Feuth, Jos P.M. Bökkerink, Peter M. Hoogerbrugge, and Livia Kapusta
Pediatric Blood & Cancer, 2009, Volume 52, Number 5, Page 631
Amiram Nir, Angelika Lindinger, Manfred Rauh, Benjamin Bar-Oz, Stephanie Laer, Lynn Schwachtgen, Andreas Koch, Jan Falkenberg, and Thomas S. Mir
Pediatric Cardiology, 2009, Volume 30, Number 1, Page 3
M. Rauchenzauner, E. Haberlandt, M. Ortler, T. Tatarczyk, M. Laimer, E. Trinka, and G. Luef
Journal of Neurology, 2008, Volume 255, Number 7, Page 980
Markus Rauchenzauner, Edda Haberlandt, Stefanie Foerster, Hanno Ulmer, Markus Laimer, Christoph F. Ebenbichler, Michael Joannidis, Lothar-Bernd Zimmerhackl, Jörg Stein, and Gerhard Luef
Epilepsia, 2007, Volume 48, Number 1
Douglas S Moodie
Nature Clinical Practice Cardiovascular Medicine, 2006, Volume 3, Number 7, Page 362

Comments (0)

Please log in or register to comment.
Log in