scholarly journals Metabolic implications of GH treatment in small for gestational age

2007 ◽  
Vol 157 (suppl_1) ◽  
pp. S47-S50 ◽  
Author(s):  
E M Delemarre ◽  
J Rotteveel ◽  
H A Delemarre-van de Waal
Keyword(s):  
Lipid Metabolism ◽  
Gestational Age ◽  
Growth Retardation ◽  
Small For Gestational Age ◽  
Postnatal Growth ◽  
Gh Treatment ◽  
Increased Risk ◽  
Igf I

Fetal growth retardation is associated with decreased postnatal growth, resulting in a lower adult height. In addition, a low birth weight is associated with an increased risk of developing diseases during adulthood, such as insulin resistance, type 2 diabetes mellitus, hypertension, dyslipidemia, and cardiovascular diseases. Children with persistent postnatal growth retardation, i.e., incomplete catchup growth, can be treated with human GH. The GH/IGF-I axis is involved in the regulation of carbohydrate and lipid metabolism. The question of whether treatment with GH in children born small for gestational age (SGA) has long-term implications with respect to glucose/insulin and lipid metabolism has not been answered yet. In this article, the available data are reviewed.

scholarly journals Successful Long-Term Growth Hormone Therapy in a Girl with Haploinsufficiency of the Insulin-Like Growth Factor-I Receptor due to a Terminal 15q26.2->qter Deletion Detected by Multiplex Ligation Probe Amplification

2008 ◽  
Vol 93 (6) ◽  
pp. 2421-2425 ◽  
Author(s):  
Marie J. E. Walenkamp ◽  
Sabine M. P. F. de Muinck Keizer-Schrama ◽  
Marianne de Mos ◽  
Margot E. Kalf ◽  
Hermine A. van Duyvenvoorde ◽  
...  
Keyword(s):  
Gestational Age ◽  
Growth Retardation ◽  
Small For Gestational Age ◽  
Adult Height ◽  
Gh Therapy ◽  
Igf I ◽  
Multiplex Ligation Probe Amplification ◽  
Igf Receptor

Abstract Context: Microscopically visible heterozygous terminal 15q deletions encompassing the IGF1R gene are rare and usually associated with intrauterine growth retardation and short stature. The incidence of submicroscopic deletions is unknown, as is the effect of GH therapy in this condition. Objective: The objective of the study was to describe the use of a novel genetic technique [multiplex ligation probe amplification (MLPA)] to detect haploinsufficiency of the IGF1R gene in a patient suspected of an IGF1R gene defect and evaluate the effect of long-term GH therapy. Patient: A 15-yr-old adolescent, born small for gestational age, showed persistent postnatal growth retardation, microcephaly, and elevated IGF-I levels. She had been treated with GH since the age of 5 yr. Methods: MLPA and array comparative genomic hybridization (aCGH) were performed to examine gene copy number changes. Dermal fibroblast cultures were used for functional analysis. Results: With MLPA, a deletion of one copy of the IGF1R gene was detected, defined by aCGH as a loss of 15q26.2->qter. IGF1R mRNA expression was decreased in fibroblasts. IGF-I binding and type 1 IGF receptor protein expression as well as activation of type 1 IGF receptor autophosphorylation and protein kinase B/Akt by IGF-I tended to be lower, but this did not reach statistical significance. GH treatment resulted in a good growth response and a normal adult height. Conclusions: MLPA and aCGH are useful tools to detect submicroscopic deletions of the IGF1R gene in patients born small for gestational age with persistent growth failure. The phenotype resembles that of a heterozygous inactivating IGF1R mutation. Long-term GH therapy causes growth acceleration in childhood and a normal adult height.

scholarly journals The Association Between Delivery of Small-for-Gestational-Age Neonate and Their Risk for Long-Term Neurological Morbidity

2020 ◽  
Vol 9 (10) ◽  
pp. 3199
Author(s):  
Omer Hadar ◽  
Eyal Sheiner ◽  
Tamar Wainstock
Keyword(s):  
Gestational Age ◽  
Small For Gestational Age ◽  
Developmental Disorders ◽  
Proportional Hazards Model ◽  
Survival Curve ◽  
Cohort Analysis ◽  
Cox Proportional Hazards Model ◽  
Increased Risk ◽  
Neurological Morbidity

Small-for-gestational-age (SGA) is defined as a birth weight below the 10th or below the 5th percentile for a specific gestational age and sex. Previous studies have demonstrated an association between SGA neonates and long-term pediatric morbidity. In this research, we aim to evaluate the possible association between small-for-gestational-age (SGA) and long-term pediatric neurological morbidity. A population-based retrospective cohort analysis was performed, comparing the risk of long-term neurological morbidities in SGA and non-SGA newborns delivered between the years 1991 to 2014 at a single regional medical center. The neurological morbidities included hospitalizations as recorded in hospital records. Neurological hospitalization rate was significantly higher in the SGA group (3.7% vs. 3.1%, OR = 1.2, 95% CI 1.1–1.3, p < 0.001). A significant association was noted between neonates born SGA and developmental disorders (0.2% vs. 0.1%, OR = 2.5, 95% CI 1.7–3.8, p < 0.001). The Kaplan-Meier survival curve demonstrated a significantly higher cumulative incidence of neurological morbidity in the SGA group (log-rank p < 0.001). In the Cox proportional hazards model, which controlled for various Confounders, SGA was found to be an independent risk factor for long-term neurological morbidity (adjusted hazard ratio( HR) = 1.18, 95% CI 1.07–1.31, p < 0. 001). In conclusion, we found that SGA newborns are at an increased risk for long-term pediatric neurological morbidity.

Growth Hormone Treatment in Children Born Small for Gestational Age—Adult Height and Metabolic Consequences

2010 ◽  
Vol 06 (01) ◽  
pp. 63
Author(s):  
Michelle L Klein ◽  
Robert Rapaport ◽  
◽  
Keyword(s):  
Growth Hormone ◽  
Gestational Age ◽  
Small For Gestational Age ◽  
Growth Velocity ◽  
Adult Height ◽  
Prediction Models ◽  
Short Term ◽  
Gh Treatment ◽  
Long Term Studies

Short-term studies of children born small for gestational age (SGA) who do not adequately catch up have shown that growth hormone (GH) treatment over a range of doses is both safe and effective at increasing growth velocity and height standard deviation (SD). Long-term studies have shown an improvement in adult height compared with untreated controls. Predictors of growth response include height and weight at start of GH treatment, pre-treatment growth velocity, target height, and pre-pubertal years treated with GH. Height prediction models are being developed to help maximize GH treatment response. While some short-term studies of GH treatment in SGA children have shown abnormalities in carbohydrate metabolism, long-term studies have demonstrated that these changes were transient. GH treatment has been shown to be safe and effective in increasing adult height of children born SGA. Follow-up is needed for assessment of the long-term effects of GH treatment.

scholarly journals High Serum Levels of Growth Hormone (GH) and Insulin-Like Growth Factor-I (IGF-I) during High-Dose GH Treatment in Short Children Born Small for Gestational Age

2006 ◽  
Vol 91 (4) ◽  
pp. 1390-1396 ◽  
Author(s):  
Marije van Dijk ◽  
Paul Mulder ◽  
Mieke Houdijk ◽  
Jaap Mulder ◽  
Kees Noordam ◽  
...  
Keyword(s):  
Gestational Age ◽  
Small For Gestational Age ◽  
Serum Levels ◽  
High Serum ◽  
High Dose ◽  
Gh Treatment ◽  
Igf I ◽  
Group A ◽  
Group B ◽  
Igfbp 3

Context: Epidemiological studies have indicated that high serum levels of GH and IGF-I are associated with long-term risks. Objective: The objective of the study was to evaluate the changes in serum levels of GH during overnight profiles, IGF-I, and IGF binding protein 3 (IGFBP-3) in short small for gestational age (SGA) children during GH treatment with two doses. Patients: Thirty-six prepubertal short SGA children were the subjects of this study. Intervention: Subjects received 1 (group A) or 2 (group B) mg GH/m2·d. Main Outcome Measures: At baseline and after 6 months of GH treatment, overnight GH profiles were performed, and serum IGF-I and IGFBP-3 levels were measured. Results: After 6 months, group B had significantly higher GH levels during the profile (mean, maximum, and area under the curve above zero line) than group A (P &lt; 0.009). In group B, maximum GH levels increased from 43.9–161 mU/liter (P &lt; 0.0002), and in group A, from 57.2–104 mU/liter (P = 0.002). During the profile (i.e. 12 h per day), children of group B had mean GH levels of 64.4 vs. 34.8 mU/liter in group A (P = 0.001). The IGF-I and IGF-I to IGFBP-3 ratio sd scores increased significantly in both groups, but were higher in group B than A [1.5 vs. 0.2 (P = 0.002) and 1.4 vs. 0.3 (P = 0.007), respectively]. In group B, 74% of the children had IGF-I levels in the highest quintile during GH treatment compared with 19% in group A. Conclusion: Our study shows that high-dose GH treatment in short SGA children results in high serum GH and IGF-I levels in most children. We recommend monitoring IGF-I levels during GH therapy to ensure that these remain within the normal range.

scholarly journals A novel heterozygous IGF-1 receptor mutation associated with hypoglycemia

2017 ◽  
Vol 6 (6) ◽  
pp. 395-403 ◽  
Author(s):  
R Solomon-Zemler ◽  
L Basel-Vanagaite ◽  
D Steier ◽  
S Yakar ◽  
E Mel ◽  
...  
Keyword(s):  
Gestational Age ◽  
Growth Retardation ◽  
Small For Gestational Age ◽  
Postnatal Growth ◽  
Heterozygous Mutation ◽  
Growth Disorders ◽  
Primary Fibroblast ◽  
Akt Phosphorylation ◽  
Abnormal Glucose Metabolism ◽  
Fibroblast Cultures

Mutation in the insulin-like growth factor-1 receptor (IGF1R) gene is a rare cause for intrauterine and postnatal growth disorders. Patients identified with IGF1R mutations present with either normal or impaired glucose tolerance. None of the cases described so far showed hypoglycemia. We aimed to identify the genetic basis for small for gestational age, short stature and hypoglycemia over three generations in one family. The proband, a 9-year-old male, presented in infancy with recurrent hypoglycemic episodes, symmetric intrauterine growth retardation and postnatal growth retardation. Blood DNA samples from the patient, his parents, a maternal sister and maternal grandmother underwent Sanger sequencing of the IGF1R gene. Primary skin fibroblast cultures of the patient, his mother and age- and sex-matched control donors were used for gene expression and receptor functional analyses. We found a novel heterozygous mutation (c.94 + 1g > a, D1105E) affecting the splicing site of the IGF1R mRNA in the patient, his mother and his grandmother. Primary fibroblast cultures derived from the patient and his mother showed reduced proliferation and impaired activation of the IGF1R, evident by reduced IGF1R and AKT phosphorylation upon ligand binding. In conclusion, the newly identified heterozygous missense mutation in exon 1 of IGF1R (D1105E) results in impaired IGF1R function and is associated with small for gestational age, microcephaly and abnormal glucose metabolism. Further studies are required to understand the mechanisms by which this mutation leads to hypoglycemia.

scholarly journals Increases in Bioactive IGF do not Parallel Increases in Total IGF-I During Growth Hormone Treatment of Children Born SGA

2019 ◽  
Vol 105 (4) ◽  
pp. e1291-e1298 ◽  
Author(s):  
Mathilde Gersel Wegmann ◽  
Rikke Beck Jensen ◽  
Ajay Thankamony ◽  
Jan Frystyk ◽  
Edna Roche ◽  
...  
Keyword(s):  
Gestational Age ◽  
Small For Gestational Age ◽  
Receptor Activation ◽  
High Dose ◽  
Reference Ranges ◽  
Gh Treatment ◽  
Normal Reference ◽  
Igf I ◽  
One Year

Abstract Background Some children born small for gestational age (SGA) experience supra-physiological insulin-like growth factor-I (IGF-I) concentrations during GH treatment. However, measurements of total IGF-I concentrations may not reflect the bioactive fraction of IGF-I which reaches the IGF-I receptor at target organs. We examined endogenous IGF-bioactivity using an IGF-I kinase receptor activation (KIRA) assay that measures the ability of IGF-I to activate the IGF-IR in vitro. Aim To compare responses of bioactive IGF and total IGF-I concentrations in short GH treated SGA children in the North European Small for Gestational Age Study (NESGAS). Material and method In NESGAS, short SGA children (n = 101, 61 males) received GH at 67 µg/kg/day for 1 year. IGF-I concentrations were measured by Immulite immunoassay and bioactive IGF by in-house KIRA assay. Results Bioactive IGF increased with age in healthy pre-pubertal children (n = 94). SGA children had low-normal bioactive IGF levels at baseline (-0.12 (1.8 SD), increasing significantly after one year of high-dose GH treatment to 1.1 (1.4) SD, P &lt; 0.01. Following high-dose GH, 68% (n = 65) of SGA children had a total IGF-I concentration &gt;2SD (mean IGF-I 2.8 SDS), whereas only 15% (n = 15) had levels of bioactive IGF slightly above normal reference values. At baseline, bioactive IGF (SDS) was significantly correlated to height (SDS) (r = 0.29, P = 0.005), in contrast to IGF-I (SDS) (r = 0.17, P = 0.10). IGF-I (SDS) was inversely correlated to delta height (SDS) after one year of high-dose GH treatment (r = -0.22, P = 0.02). Conclusion In contrast to total IGF-I concentrations, bioactive IGF stayed within the normal reference ranges for most SGA children during the first year of GH treatment.

Long-term GH treatment is not associated with disadvantageous changes of inflammatory markers and adipocytokines in children born small for gestational age

2007 ◽  
Vol 0 (0) ◽  
pp. 070902090319002-???
Author(s):  
Ruben H. Willemsen ◽  
Paul G. H. Mulder ◽  
Albert W. van Toorenenbergen ◽  
Anita C. S. Hokken-Koelega
Keyword(s):  
Gestational Age ◽  
Small For Gestational Age ◽  
Inflammatory Markers ◽  
Gh Treatment
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