European Multicentre Study in Children Born Small for Gestational Age with Persistent Short Stature: Comparison of Continuous and Discontinuous Growth Hormone Treatment Regimens

Phillip, Moshe; Lebenthal, Yael; Lebl, Jan; Zuckerman‐Levin, Nehama; Korpal-Szczyrska, Maria; Marques, Jorge Sales; Steensberg, Adam; Jons, Kirsten; Kappelgaard, Anne-Marie; Ibáñez, Lourdes

doi:10.1159/000173742

Cited by 11 publications

(12 citation statements)

References 75 publications

(53 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have reported previously that continuous low-dose and discontinuous mid-dose and high-dose GH regimens were associated with similar height gain in short SGA children [29]. In the present study, we extend our research and hypothesise that GH-related changes in the metabolic profile will, in these children, be dose-dependent, and thus differ according to the GH regimen.…”

Section: Introductionsupporting

confidence: 79%

“…Children were recruited at 36 study centres in 8 countries: Czech Republic, Finland, Germany, Israel, Poland, Portugal, Spain and Sweden [29]. …”

Section: Methodsmentioning

confidence: 99%

“…Patients were randomly assigned through a centralised computer system (Novo Nordisk A/S, Copenhagen, Denmark) to double-blind treatment in one of two active GH treatment groups or to a control group that was left untreated in the first year [29]. The two active treatments were continuous low-dose GH therapy (Norditropin® SimpleXx®, Novo Nordisk A/S) at 0.033 mg/kg/day for 2 years (low-dose group) or high-dose GH therapy at 0.100 mg/kg/day for a year, followed by a year of observation without treatment (high-dose group).…”

Section: Methodsmentioning

confidence: 99%

“…GH therapy was delivered daily at bedtime by subcutaneous injection, using the NordiPen® (Novo Nordisk A/S). We previously reported on the growth response to different GH administration regimens in these patients [29]. …”

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Metabolic Impact of Growth Hormone Treatment in Short Children Born Small for Gestational Age

Lebl

Lebenthal²,

Koloušková³

et al. 2011

Horm Res Paediatr

Self Cite

View full text Add to dashboard Cite

Background: Growth hormone (GH) treatment in short children born small for gestational age (SGA) may result in metabolic changes with potential long-term effects. Methods: 149 short SGA children (mean birth weight 2.0 ± 0.6 kg, age 5.5 ± 1.5 years, height standard deviation score (SDS) –3.1 ± 0.6) were randomised to: low-dose GH therapy (0.033 mg/kg/day) for 2 years; high-dose GH therapy (0.100 mg/kg/day) for 1 year, or mid-dose GH therapy (0.067 mg/kg/day) for 1 year. Leptin, ghrelin, insulin-like growth factor-I (IGF-I), IGF binding protein-1 (IGFBP-1), lipids, fasting blood glucose and fasting insulin were assessed at baseline, 12 and 24 months. Results: After 1 year of active treatment, GH significantly reduced serum ghrelin and increased IGF-I SDS and insulin levels. Regression analysis showed an inverse correlation between ghrelin and IGF-I SDS (p < 0.001). Leptin and IGFBP-1 also declined (both p < 0.05). Changes in insulin levels reversed upon discontinuation. Improvements in lipid profile were nonsignificant and fasting blood glucose levels remained within the normal range. Conclusion: In short SGA children, ghrelin and leptin reductions associated with GH treatment may occur through a negative feedback loop of the GH–IGF-I axis. Consequently, via ghrelin and leptin suppression, GH treatment may modify food intake and body composition and potentially improve long-term metabolic outcomes.

show abstract

Section: Introductionsupporting

confidence: 79%

“…Children were recruited at 36 study centres in 8 countries: Czech Republic, Finland, Germany, Israel, Poland, Portugal, Spain and Sweden [29]. …”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Metabolic Impact of Growth Hormone Treatment in Short Children Born Small for Gestational Age

Lebl

Lebenthal²,

Koloušková³

et al. 2011

Horm Res Paediatr

Self Cite

View full text Add to dashboard Cite

show abstract

“…IGF-IR gene anomaly should be considered in those patients presenting with 1) low birth weight and birth height (< -1.5 SD), 2) a familial history of low birth weight, 3) a normal or increased IGF-I level, 4) a normal or increased GH response to GH stimulation test, 5) lower response to GH treatment than common SGA short stature. some 15q26 has also been reported [18][19][20][21][22][23]. Compared to patients with a heterozygous mutation of the IGF-IR gene, patients with loss of the IGF-IR gene tend to have more phenotypic abnormality; not only intrauterine growth retardation and postnatal growth failure, but also microcephaly, facial abnormalities including high arched palate, abnormal ears, hypertelorism, and skeletal abnormalities like clinodactyly, club feet and scoliosis.…”

Section: Resultsmentioning

confidence: 99%

Familial short stature with IGF-I receptor gene anomaly [Review]

2012

View full text Add to dashboard Cite

Abstract. Type I insulin-like growth factor receptor (IGF-IR) is widely expressed across many cell types in fetal and postnatal tissues. The activation of this receptor after the binding of secreted IGF-I and IGF-II promotes cell differentiation and proliferation. IGF-IR has an important role in normal fetal and postnatal growth and development. IGF-IR gene anomalies presenting with intrauterine and postnatal growth retardation have recently been reported in some families. Familial short stature with IGF-IR gene anomaly is considered rare, and the clinical condition and features remain unknown. IGF-IR gene anomaly such as heterozygous IGF-IR mutation or haploinsufficiency of the IGF-IR gene should be investigated in those patients presenting with 1) low birth weight and birth height (< -1.5 SD), 2) a familial history of low birth weight, 3) a normal or increased IGF-I level, 4) a normal or increased GH response to the GH stimulation test, and/or 5) less response to GH treatment than common small for gestational age (SGA) short-stature patients. In this review, we provide an overview of current knowledge of familial short stature with IGF-IR gene anomaly.Key words: Insulin-like growth factor (IGF), IGF-I receptor, Intrauterine and postnatal growth retardation, Short stature Type I insulin-like growth factor receptor (IGF-IR) is widely expressed across many cell types in fetal and postnatal tissues. The activation of this receptor after the binding of the secreted growth factor ligands IGF-I and IGF-II elicits a repertoire of cellular responses, including the proliferation and protection of cells from programmed cell death or apoptosis [1,2]. This signaling results in fetal somatic growth, whereas this postnatal somatic growth is achieved through the synergistic interaction of the growth hormone (GH) and IGFs. IGF-IR has an important role in normal fetal and postnatal growth and development [3,4].Intrauterine growth retardation is a common condition in newborns, in which fetal events constrain birth size, and 10-20% of children born small for their gestational age (SGA) remain short into adulthood. The birth weight of IGF-IR knockout mice is 45% of normal, but they die within minutes of birth due to respiratory failure [3,4]. Thus, it has been assumed that mutations in the IGF-IR gene are probably not a common cause of intrauterine growth retardation (IUGR) in humans [5]. However, recently heterozygous IGF-IR mutations presenting with intrauterine and postnatal growth retardation have been observed in10 families [6][7][8][9][10][11][12][13], including a patient we had previously reported [9]. In this review, we describe current knowledge of familial short stature with IGF-IR gene anomaly. IGFs knock-out miceThe first paper from Liu JP, Baker J and colleagues revealed the essential role of IGFs in promoting fetal and postnatal growth by presenting the phenotype of igf1 - /-, igf2-/-, igf1r -/-, igf2r-/-[3, 4]. Mice lacking either the igf1 or igf2 genes exhibited intrauterine growth retardation, with weights approxi...

show abstract

Growth and body composition in very young SGA children

2010

View full text Add to dashboard Cite

Infants with a very low birth weight are at risk of a reduced number of nephrons predisposing to kidney disorder, hypertension, and metabolic syndrome. Approximately 3% of infants are born small for gestational age (SGA), defined as birth weight and/or length at least 2 SD below the mean for gestational age (GA), independently of whether these children are born prematurely or at term. About 10% of these children do not show postnatal catch-up growth and remain of short stature during childhood. Most of these infants are not growth hormone (GH)-deficient, but may have GH resistance. Although GH-resistant, the majority of patients benefit from GH therapy, normalize height during childhood, maintain a normal growth velocity during puberty, and attain a normal adult height. To date, GH has been shown to be safe and no significant adverse effects have been demonstrated. Children with congenital chronic kidney disease (CKD) are born with subnormal birth weight and length and about 25% are born SGA. Shortness and need for GH treatment is highly correlated with weight at birth and gestational age. Primary renal disorders modify the response to GH treatment. Analysis of whether SGA is an additional risk factor for CKD regarding the development of hypertension, metabolic syndrome and cardiovascular complications is required.

show abstract

European Multicentre Study in Children Born Small for Gestational Age with Persistent Short Stature: Comparison of Continuous and Discontinuous Growth Hormone Treatment Regimens

Cited by 11 publications

References 75 publications

Metabolic Impact of Growth Hormone Treatment in Short Children Born Small for Gestational Age

Metabolic Impact of Growth Hormone Treatment in Short Children Born Small for Gestational Age

Familial short stature with IGF-I receptor gene anomaly [Review]

Growth and body composition in very young SGA children

Contact Info

Product

Resources

About