Plasma Amino-Terminal Pro C-Type Natriuretic Peptide in the Neonate: Relation to Gestational Age and Postnatal Linear Growth

2008 ◽  
Vol 93 (1) ◽  
pp. 225-232 ◽  
Author(s):  
Timothy C. R. Prickett ◽  
Bronwyn Dixon ◽  
Chris Frampton ◽  
Timothy G. Yandle ◽  
A. Mark Richards ◽  
...  

Abstract 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.

2007 ◽  
Vol 92 (11) ◽  
pp. 4294-4298 ◽  
Author(s):  
Robert C. Olney ◽  
Timothy C. R. Prickett ◽  
Timothy G. Yandle ◽  
Eric A. Espiner ◽  
Joan C. Han ◽  
...  

Abstract Context: C-type natriuretic peptide (CNP), a paracrine factor of the growth plate, plays a key role in stimulating bone growth. The amino-terminal propeptide of CNP (NTproCNP) is produced in equimolar amounts with CNP and is measurable in plasma, providing a potential biomarker for growth plate activity and, hence, linear growth. Objective: We explored the effects of puberty, testosterone, and GH treatment on NTproCNP levels in normal and short-statured children. Design: This was a retrospective analysis of samples obtained during previous studies. Setting: The study was conducted at a pediatric clinical research center. Subjects: Children with short stature due to GH deficiency, idiopathic short stature (ISS), or constitutional delay of growth and maturation (CDGM) were studied (n = 37). A cohort of normal-statured adolescent boys was also studied (n = 23). Interventions: Children with GH deficiency and ISS were studied before and during testosterone and/or GH treatment. Boys with CDGM and healthy controls were studied once. Main Outcome Measures: The main outcomes were NTproCNP levels before and during growth-promoting therapy and during pubertal growth. Results: Children with short stature due to GH deficiency, ISS, or CDGM had comparable baseline levels of NTproCNP, and levels increased markedly in response to GH or testosterone treatment. In boys with CDGM, levels were comparable with height-matched controls but were less than those from age-matched controls. In healthy boys, NTproCNP appears to peak with the pubertal growth spurt. Conclusions: NTproCNP levels increase during growth-promoting therapy and are increased during puberty in boys. This novel biomarker of growth may have clinical utility in the evaluation of children with short stature and for monitoring growth-promoting therapy.


2011 ◽  
Vol 212 (2) ◽  
pp. 217-225 ◽  
Author(s):  
T C R Prickett ◽  
J C Bothwell ◽  
T G Yandle ◽  
A M Richards ◽  
E A Espiner

Studies from genetic modification and spontaneous mutations show that C-type natriuretic peptide (CNP) signalling plays an essential part in postnatal endochondral growth, but measurement of CNP proteins and changes in their abundance in tissues and plasma during normal growth has not been reported. Using rodent pups with GH deficiency, we now describe the pharmacodynamic response of CNP and rat amino-terminal proCNP (NTproCNP) in plasma and tissues, and relate these to changes in linear growth (nose–tail length, tibial length and tibial growth plate width) during the course of 1 week of GH or saline (control) administration. Compared with saline, significant increases in plasma and tissue CNP forms were observed after 24 h in GH-treated pups and before any detectable change in linear growth. Whereas CNP abundance was increased in most tissues (muscle, heart and liver) by GH, enrichment was the greatest in extracts from growth plates and kidney. Plasma and tissue concentrations in GH-treated pups were sustained or further increased at 1 week when strong positive associations were found between plasma NTproCNP and linear growth or tissue concentrations. High content of NTproCNP in kidney tissue strongly correlated with plasma concentrations, which is consistent with previous data showing renal extraction of the peptide. In showing a prompt and significant increase in CNP in tissues driving normal endochondral growth, these findings provide further rationale for CNP agonists in the treatment of growth disorders resistant to current therapies and support the use of CNP concentrations as biomarkers of linear growth.


2013 ◽  
Vol 98 (2) ◽  
pp. 523-532 ◽  
Author(s):  
Raquel M. Carneiro ◽  
Linda Prebehalla ◽  
Mary Beth Tedesco ◽  
Susan M. Sereika ◽  
Caren M. Gundberg ◽  
...  

Abstract Context: The African-American skeleton is resistant to PTH; whether it is also resistant to PTHrP and the hormonal milieu of lactation is unknown. Objectives: The objective of the study was to assess bone turnover markers in African-Americans during lactation vs Caucasians. Design and Participants: A prospective cohort study with repeated measures of markers of bone turnover in 60 African-American women (3 groups of 20: lactating, bottle feeding, and healthy controls), compared with historic Caucasian women. Setting: The study was conducted at a university medical center. Outcome Measures: Biochemical markers of bone turnover and calcium metabolism were measured. Results: 25-Hydroxyvitamin D (25-OHD) and PTH were similar among all 3 African-American groups, but 25-OHD was 30%–50% lower and PTH 2-fold higher compared with Caucasians (P < .001, P < .002), with similar 1,25 dihydroxyvitamin D [1,25(OH)2D] values. Formation markers [amino-terminal telopeptide of procollagen-1 (P1NP) and bone-specific alkaline phosphatase (BSAP)] increased significantly (2- to 3-fold) in lactating and bottle-feeding African-American women (P1NP, P < .001; BSAP, P < .001), as did resorption [carboxy-terminal telopeptide of collagen-1 (CTX) and serum amino-terminal telopeptide of collagen 1 (NTX), both P < .001]. P1NP and BSAP were comparable in African-American and Caucasian controls, but CTX and NTX were lower in African-American vs Caucasian controls. African-American lactating mothers displayed quantitatively similar increases in markers of bone formation but slightly lower increases in markers of resorption vs Caucasians (P = .036). Conclusions: Despite reported resistance to PTH, lactating African-American women have a significant increase in markers of bone resorption and formation in response the hormonal milieu of lactation. This response is similar to that reported in Caucasian women despite racial differences in 25-OHD and PTH. Whether this is associated with similar bone loss in African-Americans as in Caucasians during lactation is unknown and requires further study.


2012 ◽  
Vol 76 (6) ◽  
pp. 790-796 ◽  
Author(s):  
Belinda J. Schouten ◽  
Timothy C. Prickett ◽  
Penelope J. Hunt ◽  
A. Mark Richards ◽  
Mitchell E. Geffner ◽  
...  

2010 ◽  
Vol 103 (12) ◽  
pp. 1706-1710 ◽  
Author(s):  
Nicola M. Lowe ◽  
Soma R. Mitra ◽  
Peter C. Foster ◽  
Issak Bhojani ◽  
John F. McCann

Suboptimal vitamin D status among the South Asian UK population is widely reported; however, its impact on bone health is unclear. The aim of the present study was to conduct a comparative investigation of vitamin D status in postmenopausal South Asian (SA) and Caucasian (C) women and its relationship to parathyroid hormone (PTH) concentration, biochemical markers of bone turnover and bone quality. A cross-sectional study of community-dwelling women aged 50–66 years was carried out. A total of sixty-six SA women of Pakistani origin and forty-two C women living in the same community were recruited. Fasting blood was taken for the measurement of vitamin D, PTH and biochemical markers of bone turnover, including type-1 collagen β C-telopeptide (βCTX), procollagen type-1 amino-terminal propeptide (P1NP), and bone-specific alkaline phosphatase (BAP) activity. Bone quality was assessed using broadband ultrasound attenuation (BUA). Total serum 25-hydroxyvitamin D (25(OH)D) was significantly lower in the SA women than the C women (medians: SA 10·5 v. C 47·1 nmol/l; P < 0·001) This was associated with a significantly elevated serum PTH concentration in the SA group (medians: SA 7·3 v. C 4·5 pmol/l; P < 0·01). BAP activity was also significantly higher in the SA group, indicating elevated osteoblast activity and bone turnover (medians: SA 23·0 v. C 20·0 U/l; P < 0·05). No significant differences were observed between the two groups for P1NP, βCTX or BUA. Although the SA women had significantly higher serum PTH and lower 25(OH)D concentrations than C women, this was not associated with significantly higher markers of bone resorption, or reduced bone quality in the SA women.


2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
J. L. Bowtell ◽  
S. R. Jackman ◽  
S. Scott ◽  
L. J. Connolly ◽  
M. Mohr ◽  
...  

We aimed to study whether short-duration vibration exercise or football sessions of two different durations acutely changed plasma markers of bone turnover and muscle strain. Inactive premenopausal women (n=56) were randomized to complete a single bout of short (FG15) or long duration (FG60) small sided football or low magnitude whole body vibration training (VIB). Procollagen type 1 amino-terminal propeptide (P1NP) was increased during exercise for FG15 (51.6±23.0 to 56.5±22.5 μg·L−1, mean ± SD, P<0.05) and FG60 (42.6±11.8 to 50.2±12.8 μg·L−1, P<0.05) but not for VIB (38.8±15.1 to 36.6±14.7 μg·L−1, P>0.05). An increase in osteocalcin was observed 48 h after exercise (P<0.05), which did not differ between exercise groups. C-terminal telopeptide of type 1 collagen was not affected by exercise. Blood lactate concentration increased during exercise for FG15 (0.6±0.2 to 3.4±1.2 mM) and FG60 (0.6±0.2 to 3.3±2.0 mM), but not for VIB (0.6±0.2 to 0.8±0.4 mM) (P<0.05). Plasma creatine kinase increased by 55±63% and 137±119% 48 h after FG15 and FG60 (P<0.05), but not after VIB (26±54%, NS). In contrast to the minor elevation in osteocalcin in response to a single session of vibration exercise, both short and longer durations of small sided football acutely increased plasma P1NP, osteocalcin, and creatine kinase. This may contribute to favorable effects of chronic training on musculoskeletal health.


2009 ◽  
Vol 79 (56) ◽  
pp. 297-307 ◽  
Author(s):  
Laila Hussein ◽  
Sahar Abdel Aziz ◽  
Salwa Tapouzada ◽  
Boehles

Objective:Cobalamin (B12) deficiency has been reported in infants born to mothers with low cobalamin intake. Early diagnosis of vitamin B12 deficiency in infants is critical for the prevention of neurobehavioral disorders. We investigated the relationship between serum vitamin B12 level in newborns and in their healthy mothers who consumed an omnivorous diet. Anthropometry was studied longitudinally to assess the growth velocity of the infants. Urinary methylmalonic acid (MMA) excretion of 6-month old infants was compared retrospectively as the biomarker correlated with the initial serum vitamin B12 concentrations. Methods: Serum cobalamin and blood hemoglobin were determined in 84 pairs of newborns and their mothers. Urinary MMA excretion was measured in the same subjects during the first 6 months of the post partum period. Results: At birth, median serum cobalamin levels were 152.0 pmol/L in the mothers and 296.6 pmol/L in the newborns. Maternal and neonatal serum cobalamin levels had no effect on growth velocity during the first six months of postnatal life. Serum maternal and neonatal cobalamin levels were inversely associated with urinary MMA excretion. Conclusion: Early diagnosis of vitamin B12 status in neonates and infants is crucial, particularly in nutritionally deprived areas. Biochemical measurement of plasma cobalamin or its metabolic marker MMA is highly recommended. Urinary MMA measurement in cobalamin diagnostics provides an advantage in that blood sampling is not required. A vitamin B12 taskforce should be created to alleviate vitamin deficiency and its negative consequences.


2000 ◽  
Vol 6 (2) ◽  
pp. 130-139 ◽  
Author(s):  
Duncan J. Campbell ◽  
Kenneth I. Mitchelhill ◽  
Stephen M. Schlicht ◽  
Russell J. Booth

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