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Clinical Chemistry 50: 2465, 2004; 10.1373/clinchem.2004.040253
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(Clinical Chemistry. 2004;50:2465.)
© 2004 American Association for Clinical Chemistry, Inc.

Letters to the Editor

Reference Values for N-Terminal Pro-B-Type Natriuretic Peptide in Umbilical Cord Blood

Jaap Bakker1,a, Inge Gies2, Barbara Slavenburg2, Otto Bekers1, Tammo Delhaas2 and Marja van Dieijen-Visser1

Departments of1 Clinical Chemistry and2 Pediatrics, University Hospital Maastricht, Maastricht, The Netherlands

aAddress correspondence to this author at: Department of Clinical Chemistry, University Hospital Maastricht, PO Box 5800, NL-6202 AZ Maastricht, The Netherlands. Fax 31-43-3874667; e-mail j.bakker{at}klinchem.azm.nl.


To the Editor:

Plasma concentrations of B-type natriuretic peptide (BNP), a 32-amino acid peptide hormone secreted by the myocardium, increase in response to myocardial stretch or strain (1)(2). On secretion, proBNP, the storage form of BNP, is cleaved into the inactive N-terminal proBNP (NT-proBNP) and the endocrinologically active BNP. In patients with heart failure, plasma BNP concentrations are related to the severity of symptoms and underlying cardiac abnormality (3). It is also known that neonates show transient increases in both plasma NT-proBNP and BNP in the first days of life as a result of the increased left ventricular volume load induced by the circulatory changes after birth (4). After closure of the ductus arteriosus and the foramen ovale and stabilization of the forced circulatory change, plasma NT-proBNP and BNP concentrations are still increased but decrease to "adult" values in the following months (5). Although a small study was published on NT-proBNP and fetal heart rate abnormalities (6), little is known regarding umbilical cord blood BNP or NT-proBNP concentrations. The purpose of the present study was to establish reference values for NT-proBNP concentrations in umbilical cord blood.

Of the 71 successively born neonates enrolled in the study, 67 were delivered by vaginal delivery and 4 by cesarean section. Gestational age ranged from 32 to 42 weeks. After early clamping of the cord, blood was drawn from the arterial and venous umbilical cord vessels. NT-proBNP was measured with an electrochemiluminescence immunoassay (Elecsys® 2010; Roche).

Mean (SD) NT-proBNP concentrations were 79.5 (42.9) and 79.9 (45.0) pmol/L for arterial and venous umbilical cord blood, respectively. NT-proBNP concentrations in arterial and venous umbilical cord blood, plotted against each other, are shown in Fig. 1 . There was no significant mean difference in NT-proBNP concentrations between arterial and venous umbilical cord blood (paired-sample t-test). In the studied group of newborns, we found no influence of gestational age, umbilical cord pH, or mode of delivery on NT-proBNP concentrations in the umbilical cord. The maternal NT-proBNP concentration was measured in eight cases and appeared to be within the adult reference interval. In all cases, large differences were found between maternal and neonatal NT-proBNP concentrations, suggesting no placental exchange of NT-proBNP. The high concentrations of NT-proBNP in umbilical cord blood compared with the reference interval for healthy adults (0–10 pmol/L) might be explained by the differences in cardiac output and ventricular stroke volume. The ventricular volume loads in fetal and neonatal life cause a constant myocardial stretch, leading to secretion of proBNP. Moreover, the growing fetal heart up-regulates the genes for the different natriuretic peptides (1).



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  		Figure 1. Relationship between NT-proBNP concentrations (pmol/L) in arterial and venous umbilical cord blood.

Equation for the line: y = 1.0064x + 0.2251 pmol/L (R2 = 0.9587).

This study established reference values for plasma concentrations of NT-proBNP in the umbilical artery and vein, the mean concentrations being ~80 pmol/L for both vessels when measured with an electrochemiluminescence immunoassay. Further studies will focus on BNP and NT-proBNP and the role of these natriuretic peptides in perinatal medicine.


Acknowledgments

We thank Vincent Kleijnen and Michel Sliepen for expert technical assistance in measuring NT-proBNP concentrations.


References

  1. Cameron V, Aitken G, Ellmers L, Kennedy M, Espiner E. The sites of gene expression of atrial, brain, and C-type natriuretic peptides in mouse fetal development: temporal changes in embryos and placenta. Endocrinology 1996;137:817-824.[Abstract]
  2. Cameron VA, Ellmers LJ. Minireview: natriuretic peptides during development of the fetal heart and circulation. Endocrinology 2003;144:2191-2194.[Abstract/Free Full Text]
  3. Clerico A. Pathophysiological and clinical relevance of circulating levels of cardiac natriuretic hormones: are they merely markers of cardiac disease?. Clin Chem Lab Med 2002;40:752-760.[CrossRef][ISI][Medline] [Order article via Infotrieve]
  4. 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;112:896-899.[Abstract/Free Full Text]
  5. 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;93:603-607.[CrossRef][ISI][Medline] [Order article via Infotrieve]
  6. Fleming SM, O’Gorman T, O’Byrne L, Grimes H, Daly KM, Morrison JJ. Cardiac troponin I and N-terminal pro-brain natriuretic peptide in umbilical artery blood in relation to fetal heart rate abnormalities during labor. Pediatr Cardiol 2001;22:393-396.[ISI][Medline] [Order article via Infotrieve]



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