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 A Nir 1 , B Bar-Oz 2 , Z Perles 1 , R Brooks 3 , A Korach 4 and AJJT Rein 1 Unit of Paediatric Cardiology 1 , Neonatology 2 , Paediatrics 3 , and Cardiothoracic Surgery 4 , Hadassah Medical Centre, Jerusalem, Israel 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 and in infants and children with heart diseases. Acta Pædiatr 2004; 93: 603–607. Stockholm. ISSN 0803-5253 Aim: Determination of plasma levels of N-terminal pro-B-type natriuretic peptide (N-BNP) in infants and children with and without heart diseases. Methods: Plasma N-BNP was measured in 78 infants and children without heart disease and in 55 infants and children with heart disease causing volume and pressure overload. Heart diseases included chronic dilated cardiomyopathy, acute left ventricular dysfunction, and congenital cardiac anomalies resulting in left and right ventricular volume or pressure overload. The Mann-Whitney rank-sum test and the ANOVA for ranks test were used to compare two or more groups, respectively. Results: N-BNP levels were elevated in the first days of life but were not significantly different in children from 4 mo to 15 y old. The upper limit in children older than 4 mo with no heart disease was 349 pg/ml. In patients with heart disease, N-BNP levels were significantly higher than in control children (p < 0.0001). Conclusion: N-BNP levels are elevated in the first days of life and are stable from age 4 mo to adolescence. Elevated N-BNP levels reflect cardiac dysfunction in infants and children. Key words: Cardiac function, congenital heart disease, natriuretic peptides, reference values Amiram Nir, Paediatric Cardiology, Hadassah University Hospital, PO Box 12000, Jerusalem 91120, Israel (Tel. 972 68685153, fax. 972 26555437, e-mail. amiramn@md.huji.ac.il) B-type natriuretic peptide (BNP), a member of the natriuretic peptide family, is produced in cardiac myocytes and secreted into the circulation in response to cardiac volume load, causing diuresis, natriuresis and vasodilatation, as well as inhibition of the renin- aldosterone system and sympathetic activity (1). Circu- lating levels of BNP are elevated in patients with congestive heart failure and correlate with the severity of heart failure and ventricular dysfunction (2). BNP is an important component of the adaptive mechanism that helps unload the failing myocardium through systemic vasodilatation, and reduction in venous return and vascular volume (3). In recent years, BNP has emerged as a very sensitive biochemical marker for cardiac dysfunction in adults (4). BNP levels were found to be elevated in both symptomatic and asymptomatic pa- tients with left ventricular dysfunction. It is a marker for both systolic and diastolic dysfunction (5). It can be used as a guide for the response to therapy (6), and its levels correlate with prognosis (7, 8). Recently, an assay to measure the N-terminal segment of the pro-hormone proBNP (N-BNP) was developed (9). This peptide is secreted into the circulation along with BNP from myocytes, and thus reflects BNP secretion. It has a longer half-life and is easier to measure (10). N-BNP has been found to be elevated in adults with congestive heart failure and to predict prognosis and response to medical therapy (11). N-BNP-guided therapy was reported to be better than traditional therapy for patients with heart failure (12). BNP and N-BNP appear to be equivalent diagnostic and prognostic markers (13). Limited data are available on N-BNP levels in infants and children (14, 15). The purpose of this study was to measure N-BNP values in infants and children without heart disease or acute illness and to establish age-related reference values. These values were compared to those of patients with haemodynamically significant heart disease. Patients and methods The study was approved by the ethical committee of the hospital. Informed consent was obtained from parents before taking blood for N-BNP levels. Plasma N-BNP was measured from blood collected after birth in healthy newborns with no foetal distress during labour and normal physical examination and clinical course. It was measured in infants and children with no known heart disease and no acute illness who had complete blood count as part of ambulatory evaluations (before elective surgery, endocrinological workup, routine  2004 Taylor & Francis. ISSN 0803-5253 Acta Pñdiatr 93: 603±607. 2004 DOI 10.1080/08035250410025799