Markers of Type I and Type III Collagen Turnover, Insulin-Like Growth Factors, and Their Binding Proteins in Cord Plasma of Small Premature Infants: Relationships with Fetal Growth, Gestational Age, Preeclampsia, and Antenatal Glucocorticoid Treatment

Intermittent umbilical cord compression with resultant fetal hypoxia can have a negative impact on fetal growth and development. Insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are the most important regulators of fetal growth. In preterm (107-108 days of gestation) and near-term (128-131 days of gestation) ovine fetuses, we have determined the effect of intermittent umbilical cord occlusion (UCO) over a period of 4 days on the profile and expression of IGFs and IGFBPs. In experimental group animals (preterm n=7; near term n=7) UCOs were carried out by complete inflation of an occluder cuff (duration 90 s) every 30 min for 3-5 h each day, while control fetuses (preterm n=7; near term n=7) received no UCOs. Ewes were euthanized at the end of day 4, and fetal heart, lung, kidney, liver, skeletal muscle and placenta were collected. During UCOs, PO(2! ) fell (by approximately 13 mmHg), pH fell (by approximately 0.05) and PCO(2) increased (by approximately 7 mmHg), and changed to a similar extent in both preterm and near-term groups. In both preterm and near-term groups, there was no difference in fetal body or organ weight between UCO and control fetuses. No significant changes were observed in plasma IGF-I and -II concentrations or IGFBP-1, -2, -3 or -4 levels throughout the 4-day study at either gestational age. In the preterm group UCO fetuses, IGF-II mRNA (1.2-6.0 kb) levels were lower in fetal lung (33%, P<0.05), heart (54%, P<0.01) and skeletal muscle (29%, P<0.05), but there were no differences in IGF-I mRNA levels (7.3 kb); IGFBP-2 mRNA (1.5 kb) levels were lower in the right lobe of the liver (42%, P<0.05) and kidney (22%, P<0.01), but hig! her in the heart (72%, P<0.01), while IGFBP-4 (2.4 kb) levels were lower in skeletal muscle (21%, P<0.01). In the near-term group UCO fetuses, IGFBP-2 mRNA levels were greater in the placenta (39%, P<0.05). Thus, intermittent UCO as studied has a greater effect on the expression of genes encoding certain peptides of the fetal IGF system in selected tissues in preterm fetuses than that in near-term fetuses. Altered IGFBP-2 mRNA levels with reduced IGF-II mRNA levels in selected tissues may mediate changes in growth and/or differentiation that might become apparent if the length of the UCO study were extended.

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Ghrelin, Leptin, IGF-1, IGFBP-3, and Insulin Concentrations at Birth: Is There a Relationship with Fetal Growth and Neonatal Anthropometry?

Clinical Chemistry ◽

10.1373/clinchem.2007.095299 ◽

2008 ◽

Vol 54 (3) ◽

pp. 550-558 ◽

Cited By ~ 84

Author(s):

Claudio Chiesa ◽

John F Osborn ◽

Cristina Haass ◽

Fabio Natale ◽

Marina Spinelli ◽

...

Keyword(s):

Growth Factors ◽

Fetal Growth ◽

Gestational Age ◽

Head Circumference ◽

Serum Glucose ◽

Birth Length ◽

Large For Gestational Age ◽

Appropriate For Gestational Age ◽

Igfbp 3 ◽

Insulin Like Growth Factors

Abstract Background: Insulin, growth hormone (GH), and growth factors (insulin-like growth factors [IGFs] and their binding proteins [IGFBPs]) are known to influence fetal growth and also the synthesis/secretion of the recently discovered hormones leptin and ghrelin. Methods: In 153 delivering mothers and their offspring at birth, we prospectively investigated the association between mothers’ and babies’ serum concentrations of ghrelin, leptin, insulin, IGF-1, and IGFBP-3 and neonatal anthropometric characteristics and the growth of the fetus. We also tried to put babies’ serum glucose and GH measurements in this context. Results: Birth weight (BW), birth length, head circumference, and ponderal index (PI) were positively associated with cord IGF-1, IGFBP-3, and leptin and negatively associated with GH. BW was independently associated with maternal stature and prepartum weight, birth length with maternal stature, PI with maternal insulin and prepartum weight, and head circumference with maternal ghrelin. Compared with preterm infants whose development was appropriate for gestational age (AGA), preterm growth-restricted babies displayed alteration in GH-IGF axis (increased GH and low IGF-1 and IGFBP-3 concentrations), low leptin and glucose concentrations, and increased ghrelin concentrations. In large-for-gestational-age (LGA) babies, leptin, IGFBP-3, insulin, and glucose concentrations were significantly higher in asymmetric LGA newborns than in symmetric LGA and AGA newborns. Conclusions: We found relationships between metabolic factors, fetal growth, and anthropometry. Intrauterine growth restriction involved alteration in the fetal GH-IGF axis, with relatively low leptin and glucose concentrations and increased ghrelin concentrations. Leptin, insulin, and IGFBP-3 delineated subtypes of fetal overgrowth.

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Leptin, insulin, insulin-like growth factors and their binding proteins in cord serum: insight into fetal growth and discordancy

Clinical Endocrinology ◽

10.1111/j.1365-2265.2006.02632.x ◽

2006 ◽

Vol 65 (5) ◽

pp. 586-592 ◽

Cited By ~ 20

Author(s):

S. Davidson ◽

M. Hod ◽

P. Merlob ◽

B. Shtaif

Keyword(s):

Growth Factors ◽

Fetal Growth ◽

Binding Proteins ◽

Cord Serum ◽

Insight Into ◽

Insulin Like Growth Factors

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Effects of Maternal Protein Malnutrition on Fetal Growth, Plasma Insulin-like Growth Factors, Insulin-like Growth Factor Binding Proteins, and Liver Insulin-like Growth Factor Gene Expression in the Rat

Pediatric Research ◽

10.1203/00006450-199503000-00014 ◽

1995 ◽

Vol 37 (3) ◽

pp. 334-342 ◽

Cited By ~ 20

Author(s):

Séverin M Muaku ◽

Véronique Beauloye ◽

Jean-Paul Thissen ◽

Louis E Underwood ◽

Jean-Marie Ketelslegers ◽

...

Keyword(s):

Gene Expression ◽

Growth Factors ◽

Growth Factor ◽

Fetal Growth ◽

Plasma Insulin ◽

Binding Proteins ◽

Insulin Like Growth Factor ◽

Factor Gene ◽

Growth Factor Gene ◽

Insulin Like Growth Factors

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Insulin-Like Growth Factors and Their Binding Proteins in Children Born Small for Gestational Age: Implication for Growth Hormone Therapy

Hormone Research in Paediatrics ◽

10.1159/000074512 ◽

2003 ◽

Vol 60 (3) ◽

pp. 115-123 ◽

Cited By ~ 7

Author(s):

Omar Ali ◽

Pinchas Cohen

Keyword(s):

Growth Hormone ◽

Growth Factors ◽

Hormone Therapy ◽

Gestational Age ◽

Small For Gestational Age ◽

Binding Proteins ◽

Growth Hormone Therapy ◽

Insulin Like Growth Factors

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Fetal and maternal plasma insulin-like growth factors and binding proteins in pregnancies with appropriate or retarded fetal growth

Early Human Development ◽

10.1016/s0378-3782(97)01867-7 ◽

1997 ◽

Vol 49 (1) ◽

pp. 7-17 ◽

Cited By ~ 68

Author(s):

Robert Holmes ◽

Raul Montemagno ◽

Jennifer Jones ◽

Michael Preece ◽

Charles Rodeck ◽

...

Keyword(s):

Growth Factors ◽

Fetal Growth ◽

Plasma Insulin ◽

Binding Proteins ◽

Maternal Plasma ◽

Insulin Like Growth Factors

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Turnover of type I and III collagen predicts progression of idiopathic pulmonary fibrosis

Respiratory Research ◽

10.1186/s12931-021-01801-0 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

H. Jessen ◽

N. Hoyer ◽

T. S. Prior ◽

P. Frederiksen ◽

M. A. Karsdal ◽

...

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Disease Progression ◽

Real World ◽

Progressive Disease ◽

Type Iii Collagen ◽

Type I ◽

Collagen Turnover ◽

Baseline Levels ◽

Longitudinal Biomarker

Abstract Background Idiopathic pulmonary fibrosis (IPF) is characterized by the accumulation of fibrillar collagens in the alveolar space resulting in reduced pulmonary function and a high mortality rate. Biomarkers measuring the turnover of type I and III collagen could provide valuable information for prognosis and treatment decisions in IPF. Methods Serological biomarkers reflecting the formation of type III collagen (PRO-C3) and degradation of type I (C1M) and III collagen (C3M) were evaluated in a real-world cohort of 178 newly diagnosed IPF patients. Blood samples and clinical data were collected at baseline, six, and 12 months. Baseline and longitudinal biomarker levels were related to disease progression of IPF (defined as ≥ 5% decline in forced vital capacity (FVC) and/or ≥ 10% decline in diffusing capacity for carbon monoxide (DLco) and/or all-cause mortality at 12 months). Furthermore, we analysed differences in percentage change of biomarker levels from baseline between patients receiving antifibrotic treatment or not. Results Increased baseline levels of type I and III collagen turnover biomarkers were associated with a greater risk of disease progression within 12 months compared to patients with a low baseline type I and III collagen turnover. Patients with progressive disease had higher serum levels of C1M (P = 0.038) and PRO-C3 (P = 0.0022) compared to those with stable disease over one year. There were no differences in biomarker levels between patients receiving pirfenidone, nintedanib, or no antifibrotics. Conclusion Baseline levels of type I and III collagen turnover were associated with disease progression within 12 months in a real-world cohort of IPF patients. Longitudinal biomarker levels of type I and III collagen turnover were related to progressive disease. Moreover, antifibrotic therapy did not affect type I and III collagen turnover biomarkers in these patients. PRO-C3 and C1M may be potential biomarkers for a progressive disease behavior in IPF.

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