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N-terminal pro-B-type natriuretic peptide concentrations in mothers just before delivery, in cord blood, and in newborns.

To the Editor:

The role of the heart as an endocrine organ was established in 1981 by de Bold et al. (1). Usually, in adults, atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) are secreted mainly by the cardiac atria and ventricles, respectively (2). Plasma concentrations of these peptides, particularly that of BNP, have been shown to reflect cardiac dysfunction and volume overload in adults and children (3-8).

There is evidence that these peptides have possible roles during fetal life in the regulation of organogenesis of the heart and the cardiovascular system, in the regulation of blood pressure and water balance in the developing embryo, and in the transition from fetal to extra-uterine life (9). BNP may also have an important role in the regulation of amniotic fluid volume (10).

Sparse data exist regarding N-terminal proBNP (NT-proBNP) concentrations in umbilical cord blood and in the newborn during the first days of life (4, 11-13). In most of these studies, plasma concentrations of the peptide showed marked increases in the first day of life with a steady decrease during the first 5-7 days (4, 11-13).

Because NT-proBNP may be used as a marker for various pathologic conditions in perinatal medicine, we conducted a study to determine reference values for NT-proBNP in cord blood and in newborn blood compared with maternal blood.

EDTA-plasma NT-proBNP was measured in blood collected from 71 mothers just before delivery, from 122 umbilical cords, and from 33 full-term healthy newborns in the first days of life. Of 122 newborns enrolled in the study, 110 were delivered vaginally and 12 by cesarean section.

NT-proBNP was measured with an electrochemiluminescence immunoassay (Elecsys 1010/2010; Roche). The assay is unaffected by icterus (bilirubin <350 mg/L), hemolysis, or lipidemia.

The mean (SD) NT-proBNP concentration in maternal blood (n = 71) was 88.5 (44.9) ng/L, the mean concentration in cord blood (n = 122) was 578.8 (351.3) ng/L, and the mean plasma NT-proBNP concentration in the newborns (n = 33) was 3042.4 (1783.2) ng/L. For paired samples, there was a significant difference between maternal predelivery NT-proBNP concentrations and umbilical cord NT-proBNP concentrations [89.7 (45.4) vs 612.2 (364.5) ng/L, respectively; P <0.0001; n = 66]. We found no correlation between cord blood NT-proBNP concentrations and newborn weight loss.

There were no differences in NT-proBNP concentrations in cord blood and in newborns related to gender, gestational age, mode of delivery, duration of labor, or Apgar scores.

Because the reference values for the natriuretic peptides, including NT-proBNP, are assay specific (11, 14, 15), the use of different assays in the published studies makes it difficult to draw conclusions and relate to the currently published baseline values (11-13).

Our report includes NT-proBNP concentrations for 71 mothers just before delivery, 122 umbilical cord blood samples, and 33 full-term newborns (ages, 1-4 days) measured by the Roche proBNP assay. In agreement with previous studies (11-13, 16), our study shows low NT-proBNP concentrations in prelabor maternal blood, intermediate concentrations in cord blood, and high concentrations in newborn blood in the first 4 days of life. Using the same assay, Bakker et al. (13) reported a mean umbilical cord NT-proBNP concentration of ~80 pmol/L (670 ng/L), which is comparable to our result of 600 ng/L (1 pmol/L = 8.47 ng/L).

Although this study was carried out on a relatively small population of newborns, the results of our study may be used as an additional reference baseline for comparing NT-proBNP concentrations in cord blood and plasma of neonates with heart disease, pulmonary problems, or with water and electrolyte disorders in which volume overload and cardiac dysfunction are involved. The results should be compared with regard to the assay used.


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

(2.) de Lemos JA, McGuire DK, Drazner MH. B-Type natriuretic peptide in cardiovascular disease. Lancet 2003;362:316-22.

(3.) 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.

(4.) Nir A, Bar-Oz B, Perles Z, Brooks R, Korach A, Rein AJJT. N-Terminal pro-B-type natriuretic peptide. Reference plasma levels from birth to adolescence. Elevated levels at birth in infants and children with heart diseases. Acta Paediatr 2004;93:603-7.

(5.) 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.

(6.) Suda K, Matsumura M, Matsumoto M. Clinical implication of plasma natriuretic peptides in children with ventricular septal defect. Pediatr Int 2003;45:249-54.

(7.) Muta H, Ishii M, Maeno Y, Akagi T, Kato H. Quantitative evaluation of the changes in plasma concentrations of cardiac natriuretic peptide before and after transcatheter closure of atrial septal defect. Acta Paediatr 2002;91: 649-52.

(8.) Clerico A, Emdin M. Diagnostic accuracy and prognostic relevance of the measurement of cardiac natriuretic peptides: a review. Clin Chem 2004;50:33-50.

(9.) Cameron VA, Ellmers LJ. Minireview: natriuretic peptides during development of the fetal heart and circulation. Endocrinology 2003;144: 2191-4.

(10.) Bajoria R, Ward S, Chatterjee R. Brain natriuretic peptide and endothelin-1 in the pathogenesis of polyhydramnios-oligohydramnios in monochorionic twins. Am J Obstet Gynecol 2003;189:189-94.

(11.) 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.

(12.) 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.

(13.) Bakker J, Gies I, Slavenburg B, Bekers O, Delhaas T, van Dieijen-Visser M. Reference values for N-terminal pro-B-type natriuretic peptide in umbilical cord blood. Clin Chem 2004; 50:2465.

(14.) Koch A, Singer H. Normal values of B type natriuretic peptide in infants, children, and adolescents. Heart 2003;89:875-8.

(15.) Redfield MM, Rodeheffer RJ, Jacobsen SJ, Mahoney DW, Bailey KR, Burnett JC. Plasma brain natriuretic peptide concentration: impact of age and gender. J Am Coll Cardiol 2002;40: 976-82.

(16.) 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;22:393-6.

Benjamin Bar-Oz [1] * Achinoam Lev-Sagie [2] Ilan Arad [1] Lea Salpeter [3] Amiram Nir [4]

Departments of [1] Neonatology [2] Obstetrics and Gynecology and [3] Clinical Biochemistry and [4] Pediatric Cardiology Unit Hadassah and The Hebrew University Medical Center Jerusalem, Israel

DOI: 10.1373/clinchem.2005.048892

* Address correspondence to this author at: Department of Neonatology, Hadassah University Hospital, Mount Scopus, PO Box 24035, Jerusalem, Israel. Fax 972-2-5813068; e-mail or
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Title Annotation:Letters
Author:Bar-Oz, Benjamin; Lev-Sagie, Achinoam; Arad, Ilan; Salpeter, Lea; Nir, Amiram
Publication:Clinical Chemistry
Article Type:Letter to the editor
Date:May 1, 2005
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