In cardiology, B-type natriuretic peptide and the amino terminal segment of its prohormone (NT-proBNP) are important biomarkers. The importance of these peptides as markers for heart disease in pediatric cardiology is reviewed. The peptide levels are dependent on age, assay, and possibly gender. The normal value range and upper limits for infants and children are needed. To determine reference values, data were combined from four studies that measured NT-proBNP levels in normal infants and children using the same electrochemiluminescence assay. The age intervals for the upper limits of normal were chosen for intervals in which no age-dependent change was observed. Statistical analysis was performed on log-transformed data. A total of 690 subjects (47% males) ages birth to 18 years were included in the review. The levels of NT-proBNP were highest in the first days of life, then showed a marked decline in the first week or weeks. The peptide levels continued to decline gradually with age (r = 0.43; p < 0.001). Male and female levels differed only for children ages 10 to 14 years. However, the upper limit of normal did not differ between the boys and girls in any age group. The findings lead to the conclusion that B-type natriuretic peptide (BNP) and NT-proBNP are important markers for heart disease in pediatric cardiology. The levels of NT-proBNP are highest in the first days of life and decrease drastically thereafter. A mild gradual decline occurs with age throughout childhood. Girls have somewhat higher levels of NT-proBNP during puberty.

ABSTRACT. Objective. To determine plasma levels of N-terminal pro-brain natriuretic peptide (N-BNP) in control children to establish a normal age-dependent range from the neonatal period to adulthood. In addition, plasma concentrations of N-BNP were measured in children with congestive heart failure (CHF) and correlated with ejection fraction and clinical symptoms of heart failure.Methods. For establishing a normal age-dependent range of plasma N-BNP, venous blood samples were taken in 133 control patients from the neonatal period to adulthood (10 days-32 years) and in 31 children with CHF. Plasma N-BNP levels were determined by an enzyme immunoassay. In children (1 month-14 years) with CHF, plasma N-BNP levels were correlated to ejection fraction measured by echocardiography and clinical symptoms of heart failure using the Ross Score.Results. N-BNP levels in control children, adolescents, and adults did not show a significant age-related difference. In control children, the normal range was established between 150 (10th percentile) and 430 fmol/mL (90th percentile). Mean plasma N-BNP in control children was 311 fmol/mL (range: 74 -654 fmol/mL). In 31 children with CHF, the plasma N-BNP levels were significantly higher (mean: 846; range: 219-2718) than in control children. N-BNP levels showed a negative correlation with the ejection fraction (r ‫؍‬ ؊0.53) and a positive correlation with the clinical heart failure score (r ‫؍‬ 0.74).Conclusions. Plasma N-BNP levels reflect the severity of symptoms of heart failure and the impairment of cardiac function in children with CHF. In the future, determination of plasma N-BNP levels may be used as a helpful adjunct to monitor the effect of various treatments for CHF in children. Pediatrics 2002;110(6). URL: http://www.pediatrics.org/cgi/content/full/110/6/e76; N-BNP, children, heart failure, natriuretic peptides.ABBREVIATIONS. BNP, brain natriuretic peptide; N-BNP, Nterminal pro-brain natriuretic peptide; CHF, congestive heart failure; DCM, dilated cardiomyopathy; HLHS, hypoplastic left heart syndrome, FALL, postoperative tetralogy of Fallot; MR, mitral regurgitation; VSD, ventricular septal defect; AVSD, atrioventricular septal defect.T he cardiac natriuretic hormones play an important role in the regulation of extracellular fluid volume and blood pressure. These peptide hormones induce natriuresis, diuresis, and vasodilation and act specifically to counter the effects of the renin-angiotensin-aldosterone system. The natriuretic peptide system allows the heart to participate in the regulation of vascular tone and extracellular volume status. The brain natriuretic peptide (BNP) is a recently discovered natriuretic hormone of cardiac origin. 1 BNP is secreted from the cardiac ventricular myocytes in response to an increase in ventricular wall tension and is related to left ventricular filling pressures. 2 BNP mediates in arterial and venous vasodilation. Human pro-BNP consists of 108 amino acids; processing releases the biologically active 32-amino acid peptide and an ami...

The N-ANP and N-BNP plasma concentrations in healthy neonates showed a marked increase during the first days of age, suggesting that ANP and BNP have physiologic roles in the perinatal circulatory change from fetus to neonate.

No abstract

The diagnosis of Marfan syndrome (MFS) is based on evaluating a large number of clinical criteria. We have observed that many persons presenting in specialized centers for "Marfan-like" features do not have MFS, but exhibit a large spectrum of other syndromes. The spectrum of these syndromes and the distribution of "Marfan-like" features remain to be characterized. Thus, we prospectively evaluated 279 consecutive patients with suspected MFS (144 men and 135 women at a mean age of 34+/-13 years) for presence of 27 clinical criteria considered characteristic of MFS. The most frequent reasons to refer individuals for suspected MFS were skeletal features (31%), a family history of MFS, or aortic complications (29%), aortic dissection or aneurysm (19%), and eye manifestations (9%). Using established criteria, we confirmed MFS in 138 individuals (group 1) and diagnosed other connective tissue diseases, both with vascular involvement in 30 (group 2) and without vascular involvement in 39 (group 3), and excluded any distinct disease in 72 individuals (group 4). Clinical manifestations of MFS were present in all four patient groups and there was no single clinical criterion that exhibited positive and negative likelihood ratios that were per se sufficient to confirm or rule out MFS. We conclude that "Marfan-like" features are not exclusively indicative of MFS but also of numerous, alternative inherited diseases with many of them carrying a hitherto poorly defined cardiovascular risk. These alternative diseases require future study to characterize their responses to therapy and long-term prognosis.

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 (1-29 years) 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 391.5 ng/L, with higher values for younger children. The 97.5th (75th) percentile curve ranged from 319.9 ng/L (231.2 ng/L, 1-3 years) to 114.9 ng/L (53.3 ng/L, 18 years). 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 1649.7 ng/L (95% confidence interval 1546.3-1753.1 ng/L). Inter-laboratory variability ranged from 6.5% to 3.8%, covering a range from 51.3 to 6618.1 ng/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.

This study provides an example for rational drug dosage in children that copes with interpatient variability and can be easily switched to an individually guided therapy based on effective sotalol trough levels.

NT-proBNP is a reliable marker for the diagnosis of KD. Prospective clinical studies with emphasis on NT-proBNP in a diagnostic algorithm are needed.