Reference intervals for C-type natriuretic peptide plasma levels in healthy newborns and infants

Purpose: C-type natriuretic peptide (CNP), a member of natriuretic peptides, is assuming increasing importance in cardiovascular disease and, in adults, its plasma levels are related to clinical and functional disease severity. Data are scarce regarding the reference values for CNP in infancy. Aim of this study was to assess the reference intervals for CNP in healthy newborns and infants. Methods: Plasma CNP was measured in 121 apparently healthy children divided into: 41 newborns (0-3 days), 24 newborns (3-30 days), 22 infants (1-12 months) and 32 infants (1-12 years). Blood was collected from healthy newborns and infants who underwent routine screening for genetic disorder (for newborns) or an endocrine work-up (for infants). All newborns were delivered at term and presented at birth with body weight ranging from 2.5-4.1 kg and an Apgar score>=8. A group of 32 healthy adult subjects (age 64±1 years) was also studied. CNP was measured by a commercial radioimmunoassay (Phoenix Pharmaceuticals, Belmount, CA, USA). Results: Plasma CNP, measured in the 121 children, resulted significantly higher than in healthy adult subjects (13.6±1.19 pg/ml vs. 7.4±1.00 pg/ml p=0.030). When the results were analyzed as a function of the age the reference intervals for plasma CNP levels resulted: 11.6±2.06 pg/ml for newborns (0-3 days), 16.4±3.7 pg/ml for newborns (3-30 days), 15.4±2.71 pg/ml for infants (1-12 months), 13.6±2.33 pg/ml for infants (1-12 years). CNP showed the highest concentrations after the first 3 days of life with a peak between 1 and 12 months of life with a progressive decline afterwards. CNP plasma levels resulted significantly higher in newborns (3-30 days) (p=0.01) and in infants (1-12 months) (p=0.03) than in the adult subjects, respectively. There was no significant difference between CNP values found in males and females. Conclusion: Higher CNP plasma levels in children with respect to adult subjects were observed, with the highest concentration in neonates and infants. Moreover according to these data at least 3 different reference intervals should be used: one for newborns, one for infant and the last for adults. These observation may be helpful for future clinical application of CNP in children.