CONTEXT C-type natriuretic peptide (CNP) plays an essential role in endochondral bone growth. Insight into CNP's paracrine actions is possible using plasma measurements of the amino-terminal pro C-type natriuretic peptide (NTproCNP). Whether correlations of NTproCNP with linear growth, as found in children and lambs, apply in neonates is unknown. OBJECTIVES Our objective was to determine the effects of prematurity, gender, and antenatal steroids on plasma NTproCNP at birth, and serial changes in hormone concentrations, linear growth, and markers of bone turnover in the first month of postnatal life. DESIGN AND SETTING This is a prospective study of newborn infants admitted to an intensive care unit. SUBJECTS A total of 48 infants (four gestation groups) were enrolled. Umbilical cord samples were also obtained from 39 healthy term infants. MAIN OUTCOME MEASURES Plasma NTproCNP and CNP were measured in cord plasma. In enrolled neonates, serial measurements of hormone concentrations and markers of bone turnover were related to tibial growth velocity as measured by knemometry. RESULTS Cord plasma NTproCNP was inversely related to gestational age (r = -0.35; P = 0.003) and was higher in males (P < 0.001). Plasma NTproCNP (P = 0.016) and CNP (P < 0.001) increased within the first week of life, the increase relating inversely to gestational age (r = -0.64; P < 0.001). Plasma NTproCNP at 1 wk was strongly correlated with linear growth velocity (r = 0.49; P < 0.001), and also at 2-4 wk, the relation being stronger than observed between bone turnover markers and growth velocity. CONCLUSIONS In neonates with diverse disorders affecting growth and nutrition, plasma NTproCNP was strongly correlated with linear growth during the first 4 wk of postnatal life and may prove to be a novel marker of growth plate activity in neonates.