Skip to main content
SpringerLink
Log in

Reference values of NT-proBNP serum concentrations in the umbilical cord blood and in healthy neonates and children

Referenzwerte von NT-proBNPSerumkonzentrationen im Nabelschnurblut und bei gesunden Neugeborenen und Kindern

  • ORIGINAL PAPER
  • Published:
Zeitschrift für Kardiologie Aims and scope Submit manuscript

Zusammenfassung

Hintergrund

Das N-terminale BNP ist eine neurohormonale Substanz, die überwiegend von Herzmuskelzellen des linken Ventrikels und in geringerem Ausmaß auch aus der Wand des linken Vorhofs freigesetzt wird. Der Freisetzungsmechanismus wird induziert durch eine erhöhte Wandspannung infolge von Volumen- oder Druckbelastung des Ventrikels. Das aktive BNP bewirkt physiologischerweise eine Hemmung des Sympathikus, eine Vasodilatation, Natriurese und Diurese sowie eine Inhibierung des Renin-Angiotensin-Aldosteron-Systems. Aufgrund der hohen Sensitivität, Spezifität und der guten Korrelation mit dem Ausmaß der Volumenbelastung sind BNP als auch NTproBNP sensible Marker für eine ventrikuläre Dysfunktion. Es war das Ziel dieser Untersuchung, die Referenzwerte von NT-proBNP Serumkonzentrationen für das gesamte Kindes- und Jugendalter, insbesondere das Neugeborenenalter, zu bestimmen.

Methoden

In einer Querschnittsstudie wurden die NT-proBNP-Serumkonzentrationen mit Hilfe eines ElektroChemiLumineszenz ImmunoAssays („ECLIA“ Roche) gemessen. Die Bestimmungen erfolgten im Nabelschnurblut von 62 Neugeborenen und bei 222 gesunden Probanden im Alter von 0 bis 18 Jahren.

Ergebnisse

Die NT-proBNP-Konzentrationen im Nabelschnurblut lagen zwischen 281 und 2595 pg/ml (Mittelwert: 818 pg/ml). Es war ein signifikanter Anstieg der Werte während der ersten Lebenstage nachweisbar, gefolgt von einem schnellen Abfall der Konzentrationen im Verlauf des ersten Lebensjahres und einem nachfolgenden weiteren allmählichen Abfall im gesamten Kleinkindesalter; ab dem 10. Lebensjahr erreichten die Werte das Niveau des Erwachsenenalters.

Schlussfolgerung

Die Kenntnis der Referenzintervalle der NT-proBNP-Normalwerte bei gesunden Kindern dient als nichtinvasiver Parameter zur Differenzierung von pathologischen Konditionen wie Myokarditis, hypertrophische oder dilatative Kardiomyopathie, Tachyarrhythmien und pulmonalem Hochdruck.

Summary

Background:

N-terminal brain natriuretic peptide (NT-proBNP) is a neurohormonal substance secreted mainly by the cardiac myocytes of the left ventricle and to a less degree of the left atrium. The releasing mechanism is induced by an increased wall stress on the base of volume or pressure load of the ventricle. The physiologic actions of BNP are prohibition of the sympathetic activity, vasodilatation, natriuresis, diureses and inhibition of the renin-angiotensin system. Because of its high sensitivity and specifity in relation to the left ventricular incompetence, BNP as well as NTproBNP are well accepted markers of ventricular dysfunction. It was the aim of the study to establish reference values of NT-proBNP serum concentrations throughout childhood, in particular in the newborn age group.

Methods

In a cross sectional study, serum NT-proBNP concentrations were measured by an ElectroChemiLuminescenceImmunoAssay (“ECLIA” Roche) in the umbilical cord blood of 62 healthy full-term neonates and in 222 healthy probands from birth up to the age of 18 years.

Results

The concentration of NT-proBNP in the cord blood samples ranged from 281 to 2595 pg/ml (mean: 818 pg/ml). There was a significant increase in the first days of life followed by a rapid decrease during the first year and a further gradual decrease throughout infancy; beyond the 10th year of age normal adult values were approached.

Conclusions

The knowledge of the normal range of plasma NT-proBNP levels in healthy subjects during childhood serves as a non-invasive marker for differentiation of pathologic conditions such as acute myocarditis, hypertrophic or dilated cardiomyopathy, tachyarrhythmias and pulmonary hypertension.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  1. De Bold AJ, Borenstein HB, Veress AT, Sonnenberg H (1981) A rapid and potent natriuretic response to intravenous injection of atrial extracts in rats. Life Sci 28:89–94

    Article  CAS  PubMed  Google Scholar 

  2. Dillon MJ, Gillin ME, Ryness JM, de Swiet M (1976) Plasma renin activity and aldosterone concentration in the human newborn. Arch Dis Child 51:537–540

    CAS  PubMed  Google Scholar 

  3. Downie PF, Talwar S, Squire IB, Davies JE, Barnett DB, NG LL (1999) Assessment of the stability of N-terminal pro-brain natriuretic peptide in vitro: implications for assessment of left ventricular dysfunction. Clinical Science 97:255–258

    Article  CAS  PubMed  Google Scholar 

  4. Feller SM, Gagelmann M, Forssmann WG (1989) Urodilatin: a newly described member of the ANP family. Trends Pharmacol Sci 10:93–94

    Article  CAS  PubMed  Google Scholar 

  5. Fiselier TJW, Lijnen P, Monnens L, van Munster P, Jansen M, Peer P (1983) Levels of renin, angiotensin I and II angiotensin-converting enzyme and aldosterone in infancy and childhood. Eur J Pediatr 141:3–7

    Article  CAS  PubMed  Google Scholar 

  6. Gemelli M, Mami C, DeLuca F, Stelitano L, Bonaccorsi P, Martino F (1991) Atrial natriuretic peptide and reninaldosterone relationship in healthy newborn infants. Acta Paediatr Scand 80:1128–1133

    CAS  PubMed  Google Scholar 

  7. Herrmann M, Scharhag J,MicleaM, Urhausen A, Herrmann W, Kindermann W (2003) Post race kinetics of cardiac troponin T and I and N-terminal pro brain natriuretic peptide in marathon runners. Clin Chem 5:831–834

    Article  Google Scholar 

  8. Hobbs FD, Davis RC, Roalfe AK, Hare R, Davies MK, Kenkre JE (2002) Reliability of N-terminal pro-brain natriuretic peptide assay in diagnosis of heart failure: cohort study in representative and high risk community population. BMJ 324:1498–1503

    Article  CAS  PubMed  Google Scholar 

  9. Holmes SJ, Espiner EA, Richards AM, Yandle TG, Frampton C (1993) Renal, endocrine and haemodynamic effects of human brain natriuretic peptide in normal men. J Clin Endocrinol Metab 76:91–96

    Article  CAS  PubMed  Google Scholar 

  10. Hong M, Yan Q, Tao B, Boersma A, Han KK, Vantyghem MC, Racadot A, Lefebvre J (1992) Estradiol, progesterone and testosterone exposures affect the atrial natriuretic peptide gene expression in vivo in rats. Biol Chem Hoppe Seyler 373:213–218

    CAS  PubMed  Google Scholar 

  11. Hunt PJ, Richards AM, Nicholls MG, Yandle TG, Doughty RN, Espiner ER (1997) Immunoreactive amino-terminal pro-brain natriuretic peptide (NT-proBNP): a new marker of cardiac impairment. Clin Endocrin 47:287–296

    Article  CAS  Google Scholar 

  12. Hunt PJ, Yandle TG, Nicholls MG, Richards AM, Espiner EA (1995) The amino-terminal portion of pro-brain natriuretic peptide (Pro-BNP) ciculates in plasma. Biochem Biophys Res Commun 214:1175–1183

    Article  CAS  PubMed  Google Scholar 

  13. Koch A, Singer H (2003) Normal values of B-type natriuretic peptid in infants, children, and adolescents. Heart 89:875–878

    Article  CAS  PubMed  Google Scholar 

  14. Krüger C, Rauh M, Doerr HG (1998) Immunoreactive renin concentrations in healthy children from birth to adolescence. Clin Chim Acta 274:15–17

    Article  PubMed  Google Scholar 

  15. Luchner A, Holmer S, Schunkert H, Rieger GA (2003) Clinical utility of biochemical markers of heart failure (Bedeutung der Herzinsuffizienzmarker BNP und NT-proBNP für die Klinik) Dtsch Ärztebl 100:B2757–2763

    Google Scholar 

  16. McCullough PA, Omland T, Maisel AS (2003) B-type natriuretic peptides: A diagnostic breakthrough for clinicians. Reviews Cardiovasc Med 4:72–80

    Google Scholar 

  17. Meyer T, Schwaab B, Görge G, Scharhag J, Herrmann M, Kindermann W (2004) Can serum NT-proBNP detect changes of functional capacity in patients with chronic heart failure? Z Kardiol 93:540–545

    Article  CAS  PubMed  Google Scholar 

  18. Mir T, Laux R, Hellwege HH, Liedke B, Heinze C, von Buelow H, Laer S, Weil J (2003) Plasma concentrations of aminoterminal pro atrial natriuretic peptide and aminoterminal pro brain natriuretic peptide in healthy neonates: marked and rapid increase after birth. Pediatr 112:896–899

    Article  Google Scholar 

  19. Mir TS, Marohn S, Läer S, Eiselt M, Grollmus O, Weil J (2002) Plasma concentrations of N-terminal pro brain natriuretic peptide (N-BNP) in control children from the neonatal to adolescent period and in children with congestive heart failure. Pediatr 110:1243

    Google Scholar 

  20. Mukoyama M, Nakao K, Hosoda K, Suga S, Saito Y, Ogowa Y, Shirakami G, Jougasaki M, Obata K,Yasue H, Kambayashi Y, Inouye K, Imura H (1991) Brain natriuretic peptide as a novel cardiac hormone in humans. Evidence for an exquisite dual natriuretic peptide system, atrial natriuretic peptide and brain natriuretic peptide. J Clin Invest 87:1402–1412

    CAS  PubMed  Google Scholar 

  21. Nir A, Bar-Oz B, Brooks R, Korach A, Rein AJJT (2004) 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 93:603–607

    Article  CAS  PubMed  Google Scholar 

  22. Peacock WJ (2002) The B-type natriuretic peptide assay: A rapid test for heart failure. Cleveland Clin J Med 69:243–251

    Google Scholar 

  23. Rauh M, Koch A (2003) Plasma N-Terminal Pro-B-Type natriuretic peptide concentrations in control population of infants and children. Clin Chem 49:1563–1564

    Article  CAS  PubMed  Google Scholar 

  24. Raymond I, Groenning BA, Hildebrandt PR, Nilsson JC, Baumann M, Trawinski J, PedersenF (2003) The influence of age and sex and other variables on the plasma level of N-terminal pro brain natriuretic peptide in a large sample of the general population. Heart 89:745–751

    Article  CAS  PubMed  Google Scholar 

  25. Richards AM, Nicholls MG, Yandle TG, Frampton C, Espiner EA, Turner JG, Buttimore RC, Lainchbury JG, Elliott JM, Ikram H, Crozier IG, Smyth DW (1998) Plasma N-terminal probrain natriuretic peptide and adrenomedullin: new neuro-hormonal predictors of left ventricular function and prognosis after myocardial infarction. Circulation 97:1921–1929

    CAS  PubMed  Google Scholar 

  26. Schweitz H, Vigne P, Moinier D, Frelin C, Lazdunski M (1992) A new member of the natriuretic peptide family is present in the venom of the Green Mamba (Dendroaspis angusticeps). J Biol Chem 267:13928–13032

    CAS  PubMed  Google Scholar 

  27. Sudoh T, Kangawa K, Minamino N, Matsuo H (1988) A new natriuretic peptide in porcine brain. Nature 332:78–81

    Article  CAS  PubMed  Google Scholar 

  28. Sudoh T, Minamino N, Kangawa K, Matsuo H (1990) C-type natriuretic peptide: a new member of natriuretic peptide family identified in porcine brain. Biochem Biophys Res Commun 168:863–870

    Article  CAS  PubMed  Google Scholar 

  29. Troughton RW, Frampton CM, Yandle TG, Espiner EA, Nicholls MG, Richards AM (2000) Treatment of heart failure guided by plasma amino terminal brain natriuretic peptide (N-BNP) concentrations. Lancet 355:1126–1130

    Article  CAS  PubMed  Google Scholar 

  30. Tsutamoto T, Wada A, Maeda K, Hisanaga T, Mabuchi N, Hayashi M, Ohnishi M, Sawaki M, Fujii M, Horie H, Sugimoto Y, Kinoshita M (1999) Plasma brain natriuretic peptide level as a biochemical marker of morbidity and mortality in patients with symptomatic left ventricular dysfunction. Comparison with plasma angiotensin ll and endothelin-1. Eur Heart J 20:1799–1807

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Klinik für Kinderkardiologie , Universitätsklinikum des Saarlandes, 66421, Homburg/Saar, Germany

    A. Lindinger

  2. Derpartment of Pediatric Cardiology, University of the Saarland, Homburg/Saar, Germany

    L. Schwachtgen, P. Schwarz & N. Marx

  3. Institute of Clinical Chemistry and Laboratory Medicine, University of the Saarland, Homburg/Saar, Germany

    M. Herrmann

  4. Institute for Medical Biometrics Epidemiology and Medical Informatics, University of the Saarland, Homburg/Saar, Germany

    T. Georg

Authors
  1. L. Schwachtgen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Herrmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T. Georg
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P. Schwarz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. N. Marx
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. Lindinger
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. Lindinger.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schwachtgen, L., Herrmann, M., Georg, T. et al. Reference values of NT-proBNP serum concentrations in the umbilical cord blood and in healthy neonates and children. ZS Kardiologie 94, 399–404 (2005). https://doi.org/10.1007/s00392-005-0246-x

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00392-005-0246-x

Schlüsselwörter

Key words

Search

Navigation