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

Prickett, Timothy C. R.; Dixon, Bronwyn; Frampton, Chris; Yandle, Timothy G.; Richards, A. Mark; Espiner, Eric A.; Darlow, Brian A

doi:10.1210/jc.2007-1815

Cited by 39 publications

(34 citation statements)

References 38 publications

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“…Reduced CNP concentrations are also observed in umbilical blood of human newborns whose mothers were treated with glucocorticoids within 72 h of delivery (6). These findings confirm and extend these observations in showing significant inhibition of fetal CNP secretion by small increments in fetal plasma cortisol concentrations well within the range encountered in normal pregnancy.…”

Section: Discussionsupporting

confidence: 82%

“…In rapidly growing lambs, catabolic interventions such as caloric restriction (9) and high doses of glucocorticoids (7), well-recognized inhibitors of linear growth, rapidly and reversibly reduce circulating forms of CNP and markers of bone formation. Similar reductions in CNP forms occur in the fetus during maternal caloric restriction (10) or glucocorticoid administration (6). However, the effect of physiological increments in fetal cortisol on CNP synthesis is unknown.…”

Section: -Type Natriuretic Peptide (Cnp) Is An Important Growthmentioning

confidence: 99%

“…Peptide standards were made from synthetic human proCNP (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19), taking into account the purity data supplied (Chiron Technologies, Victoria, Australia).Within-and between-assay coefficients of variation were 4.9 and 6.4%, respectively, at 22 pmol/L.…”

Section: Animalsmentioning

confidence: 99%

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Effect of Cortisol on C-Type Natriuretic Peptide in Ovine Pregnancy: Differential Responses in Fetal and Placental Tissues

et al. 2010

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ABSTRACT:We have used aminoterminal pro C-type natriuretic peptide (NTproCNP)-a stable marker of CNP secretion-to study the effect of cortisol on CNP secretion and fetal growth. In ovine pregnancy, maternal plasma NTproCNP (largely sourced from the placenta) increases at the end of the first trimester and then decreases abruptly preterm during the phase of fetal surge in cortisol secretion. Postulating that increases in cortisol, as occurs in the fetal or maternal circulation in late pregnancy, will reduce CNP secretion, we studied the fetal and maternal responses in NTproCNP to sustained low-dose infusions of cortisol (1.2 mg/d/kg for 11 d) delivered to the fetus from d 117 gestation. Fetal plasma NTproCNP was progressively reduced during fetal cortisol infusions, whereas fetal girth growth was unchanged. In contrast, maternal NTproCNP was unaffected by cortisol. We conclude that fetal but not placental tissue production of CNP is reduced by small increments in fetal cortisol. Failure to reduce maternal NTproCNP may relate to the continuing presence of the placental barrier to cortisol at this stage of pregnancy. (Pediatr Res 68: 462-465, 2010) C -type natriuretic peptide (CNP) is an important growth factor expressed in a wide range of tissues (1) during development (2) and postnatal life (3). Although shown to be essential to postnatal linear growth in both rodents (4) and humans (5), CNP production has also been found to correlate strongly with linear growth velocity in lambs and throughout all phases of linear growth in humans (6 -8). In rapidly growing lambs, catabolic interventions such as caloric restriction (9) and high doses of glucocorticoids (7), well-recognized inhibitors of linear growth, rapidly and reversibly reduce circulating forms of CNP and markers of bone formation. Similar reductions in CNP forms occur in the fetus during maternal caloric restriction (10) or glucocorticoid administration (6). However, the effect of physiological increments in fetal cortisol on CNP synthesis is unknown.Recent studies of ovine pregnancy show that both CNP and the bio inactive aminoterminal fragment of pro CNP 1-103 (NTproCNP) (11) are secreted by the placenta and circulate at high concentrations in maternal plasma from the end of the first trimester (12). In contrast, the ovine placenta does not seem to contribute to circulating fetal CNP concentrations, which are much lower than maternal concentrations (12). Nonetheless, as in the human fetus (13), fetal CNP synthesis is likely to be high, as shown by the very high concentrations of NTproCNP in fetal plasma. Fetal CNP forms are clearly regulated independently of maternal concentrations (10), but the sites of synthesis and the source of NTproCNP in the fetal circulation remain to be determined.A striking feature of the pattern of maternal plasma CNP forms in healthy pregnant ewes is the sudden decline in both NTproCNP and CNP within the last week of pregnancy (12)-a phase of rapidly increasing fetal cortisol production (14). Mindful of the inhibitory effects o...

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Section: Discussionsupporting

confidence: 82%

Section: -Type Natriuretic Peptide (Cnp) Is An Important Growthmentioning

confidence: 99%

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Effect of Cortisol on C-Type Natriuretic Peptide in Ovine Pregnancy: Differential Responses in Fetal and Placental Tissues

et al. 2010

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“…The strong associations linking growth parameters to timematched plasma NTproCNP concentrations provide further support to the in vitro studies and indicate that CNP proteins are likely to materially contribute to sustained endochondral growth. In this context, it should be noted that this association (skeletal growth and plasma NTproCNP) has been established in lambs (using metacarpal growth (Prickett et al 2005)), human neonates (tibial growth (Prickett et al 2008)), children (height, i.e. largely vertebral and lower limb growth (Prickett et al 2005, Olney et al 2009) and now in rodents (nose-tail growth, tibial length and growth plate width).…”

Section: Discussionmentioning

confidence: 91%

“…We have found that plasma concentrations of NTproCNP are closely correlated with concurrent growth velocity throughout childhood (Olney et al 2007, Prickett et al 2008, suggesting that CNP production within growth plates or closely related tissue is age dependent and acts as a driver of linear growth after birth. However, no study has examined the peptide concentrations within tissues with potential to affect skeletal growth, or how the tissue concentrations may change or relate to plasma concentrations and the growth process itself.…”

Section: ) In Contrast Tomentioning

confidence: 91%

Pharmacodynamic responses of plasma and tissue C-type natriuretic peptide to GH: correlation with linear growth in GH-deficient rats

Prickett

Bothwell²,

Yandle³

et al. 2011

Journal of Endocrinology

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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.

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Urinary osteocalcin and serum pro-C-type natriuretic peptide predict linear catch-up growth in infants

Kilpeläinen

Ivaska

Kuiri-Hänninen

et al. 2012

Journal of Bone and Mineral Research

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Preterm (PT) infants are at risk of growth failure despite advanced early care and nutrition. In addition to poor weight gain, slow postnatal linear growth also is associated with adverse neurological outcome. Markers distinguishing infants at risk for impaired catch-up growth are needed. The aim of this longitudinal study was to determine the extent to which postnatal levels of circulating cartilage (serum pro-C-type natriuretic peptide [S-proCNP]) and urinary bone metabolic markers (urinary osteocalcin [MidOC] and two forms of C-terminal cross-linked telopeptide of type I collagen [U-a-CTX-I and U-b-CTX-I]) predict catch-up growth in infancy in 67 PT and 58 full-term (FT) infants. PT infants were significantly shorter than FT infants during the first 6 months of life, but no statistically significant difference was found at the corrected age of 14 months (M14). At the age of 3 months (M3), S-ProCNP and U-MidOC levels, but not U-a-CTX-I and U-b-CTX-I levels, correlated positively with prospective growth velocity from M3 to M14 (r ¼ 0.460, p < 0.001 and r ¼ 0.710, p < 0.001, respectively). In predicting slow linear growth (growth velocity at the lowest quartile), the area under the S-ProCNP ROC curve was 0.662 and that of U-MidOC 0.891. Thus, U-MidOC, and to lesser extent S-ProCNP at M3 are predictors of catch-up growth in infancy. ß

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

Cited by 39 publications

References 38 publications

Effect of Cortisol on C-Type Natriuretic Peptide in Ovine Pregnancy: Differential Responses in Fetal and Placental Tissues

Effect of Cortisol on C-Type Natriuretic Peptide in Ovine Pregnancy: Differential Responses in Fetal and Placental Tissues

Pharmacodynamic responses of plasma and tissue C-type natriuretic peptide to GH: correlation with linear growth in GH-deficient rats

Urinary osteocalcin and serum pro-C-type natriuretic peptide predict linear catch-up growth in infants

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