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.

Objective: To determine normal values of plasma B type natriuretic peptide from infancy to adolescence using a commercially available rapid assay. Setting: Tertiary referral centre. Design: The study was cross sectional. Plasma BNP concentration was measured in 195 healthy infants, children, and adolescents from birth to 17.6 years using the triage BNP assay (a fluorescence immunoassay). Results: During the first week of life, the mean (SD) plasma concentration of BNP in newborn infants decreased significantly from 231.6 (197.5) to 48.4 (49.1) pg/ml (p = 0.001). In all subjects older than two weeks plasma BNP concentration was less than 32.7 pg/ml. There was no significant difference in mean plasma BNP measured in boys and girls younger than 10 years (8.3 (6.9) v 8.5 (7.5) pg/ml). In contrast, plasma concentration of BNP in girls aged 10 years or older was significantly higher than in boys of the same age group (12.1 (9.6) v 5.1 (3.5) pg/ml, p < 0.001). Plasma BNP concentrations were higher in pubertal than in prepubertal girls (14.4 (9.7) v 7.1 (6.6) pg/ml, p < 0.001) and were correlated with the Tanner stage (r = 0.41, p = 0.001). Conclusions: Plasma BNP concentrations in newborn infants are relatively high, vary greatly, and decrease rapidly during the first week of life. In children older than 2 weeks, the mean plasma concentration of BNP is lower than in adults. There is a sex related difference in the second decade of life, with higher BNP concentrations in girls. BNP concentrations in girls are related to pubertal stage.

Introduction: Clinical variability associated with the common 22q11.2 microdeletion is well known, and has led to a broad application of FISH diagnostics with probes for loci TUPLE1 or D22S75 (N25), although, rarely reported atypical deletions associated with the same phenotypic spectrum would not be discovered by these probes. As most types of 22q11.2 deletions occur between low copy repeats within the region (LCR22), we assumed that atypical deletions should be more common than has been reported. To address this question and the possibility of a deletion size related genotype-phenotype correlation, we systematically assessed the frequency of typical and atypical 22q11.2 deletions in a large cohort of patients. Methods: We used a set of 10 fluorescent in situ hybridisation (FISH) DNA probes, capable of detecting all reported and hypothetical deletions between the LCR22, and analysed 350 patients. Deletion sizes in atypical deletions were established by use of further FISH probes. Frequency of certain atypical deletions was analysed in controls by FISH and quantitative PCR. Results: Patients with conotruncal heart defects (ctCHD) and with typical VCFS phenotype showed the common 3 Mb or nested 1.5 Mb deletions (in 18.5% and 78.6%, respectively), but no atypical deletion, while 5% (3/63) of patients with a mildly suggestive, atypical phenotype showed atypical distal deletions, which were not detected in patients with mental retardation of unknown origin or in healthy controls. Discussion: These statistically significant differences demonstrate that atypical distal 22q11.2 deletions are very uncommon in patients with ctCHDs, while atypical congenital heart defects and mild dysmorphism are recognisable feature of atypical distal deletions. Further phenotype-genotype analysis disclosed association of significant developmental delay with the distal part of the common deletion region, and choanal atresia and atypical CHDs with the adjacent distal deletion region.

Variations in the three circadian clock genes Per2, Arntl, and Npas2 are associated with the disease, supporting the hypothesis that the circadian clock mechanisms contribute to winter depression.

The particular benefit of a covering stoma is reduction in the rate of leaks requiring surgery and thus in the severe consequences of an anastomotic leakage.