The Auxological and Biochemical Continuum of Short Children Born Small for Gestational Age (SGA) or with Normal Birth Size (Idiopathic Short Stature)

Growth hormone (GH) is used to treat short stature and growth failure associated with growth disorders. Birth size and GH status variably modulate response to GH therapy. The aim of this study was to determine the effect of birth size on response to GH therapy, and to determine the impact of GH status in patients born small for gestational age (SGA) on response to GH therapy. Data from the prospective, non-interventional American Norditropin Studies: Web-Enabled Research (ANSWER) Program was analyzed for several growth outcomes in response to GH therapy over 3 years. GH-naïve children from the ANSWER Program were included in this analysis: SGA with peak GH ≥10 ng/mL (20 mIU/L), SGA with peak GH <10 ng/mL (20 mIU/L), isolated growth hormone deficiency (IGHD) born SGA, IGHD not born SGA and idiopathic short stature. For patients with IGHD, those who did not meet criteria for SGA at birth showed greater improvements in height SDS and BMI SDS than patients with IGHD who met criteria for SGA at birth. For patients born SGA, response to GH therapy varied with GH status. Therefore, unlike previous guidelines, we recommend that GH status be established in patients born SGA to optimize GH therapy.

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Association Analysis of Ten Candidate Genes in a Large Multinational Cohort of Small for Gestational Age Children and Children with Idiopathic Short Stature (NESTEGG study)

Hormone Research in Paediatrics ◽

10.1159/000355409 ◽

2013 ◽

Vol 80 (6) ◽

pp. 466-476 ◽

Cited By ~ 7

Author(s):

L.C.G. de Graaff ◽

A.J.L. Clark ◽

M. Tauber ◽

M.B. Ranke ◽

L.B. Johnston ◽

...

Keyword(s):

Short Stature ◽

Candidate Genes ◽

Association Analysis ◽

Gestational Age ◽

Small For Gestational Age ◽

Idiopathic Short Stature

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Unexpected high frequency of skeletal dysplasia in idiopathic short stature and small for gestational age patients

Acta Endocrinologica ◽

10.1530/eje-13-0864 ◽

2014 ◽

Vol 170 (5) ◽

pp. 677-684 ◽

Cited By ~ 14

Author(s):

I Flechtner ◽

K Lambot-Juhan ◽

R Teissier ◽

A Colmenares ◽

G Baujat ◽

...

Keyword(s):

Short Stature ◽

Gestational Age ◽

Small For Gestational Age ◽

Comparison Group ◽

Final Height ◽

Normal Growth ◽

Idiopathic Short Stature ◽

Skeletal Survey ◽

Genetic Syndrome ◽

The Impact

ObjectiveTo assess the prevalence of skeletal dysplasias (SDs) in patients with idiopathic short stature (ISS) or small for gestational age (SGA) status.SettingRare Endocrine/Growth Diseases Center in Paris, France.DesignA prospective study on consecutive patients with ISS and SGA enrolled from 2004 to 2009.MethodWe used a standardized workup to classify patients into well-established diagnostic categories. Of 713 patients with ISS (n=417) or SGA status (n=296), 50.9% underwent a skeletal survey. We chose patients labeled normal or with a prepubertal slowdown of growth as a comparison group.ResultsDiagnoses were ISS (16.9%), SGA (13.5%), normal growth (24.5%), transient growth rate slowing (17.3%), endocrine dysfunction (12%), genetic syndrome (8.9%), chronic disease (5.1%), and known SD (1.8%). SD was found in 20.9% of SGA and 21.8% ISS patients and in only 13.2% in our comparison group. SD prevalence was significantly higher in the ISS group than in the comparison group, especially (50%) for patients having at least one parent whose height was <−2 SDS. Dyschondrosteosis and hypochondroplasia were the most frequently identified SD, and genetic anomaly was found in 61.5 and 30% respectively. Subtle SD was found equally in the three groups and require long-term growth follow-up to evaluate the impact on final height.ConclusionSD may explain more than 20% of cases of growth retardation ascribed to ISS or SGA, and this proportion is higher when parental height is <−2 SDS. A skeletal survey should be obtained in patients with delayed growth in a context of ISS or SGA.

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The Growth Response to Growth Hormone (GH) Treatment in Children with Isolated GH Deficiency Is Independent of the Presence of the Exon 3-Minus Isoform of the GH Receptor

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2006-0063 ◽

2006 ◽

Vol 91 (10) ◽

pp. 4171-4174 ◽

Cited By ~ 68

Author(s):

Werner F. Blum ◽

Kalotina Machinis ◽

Elena P. Shavrikova ◽

Alexandra Keller ◽

Heike Stobbe ◽

...

Keyword(s):

Short Stature ◽

Outcome Measures ◽

Gestational Age ◽

Small For Gestational Age ◽

Growth Response ◽

Gh Deficiency ◽

Idiopathic Short Stature ◽

Height Velocity ◽

Gh Treatment ◽

Gh Receptor

Abstract Context: A variant of the human GH receptor (GHR) lacks a 22-amino-acid sequence derived from exon 3 (d3-GHR). It was reported that pediatric patients, born small for gestational age or with idiopathic short stature who were homozygous or heterozygous for this variant responded better to GH treatment than those homozygous for the full-length allele (fl-GHR). Objective: The objective was to study the impact of the GHR genotype on the phenotype and growth response in patients with isolated GH deficiency (IGHD) treated with GH. Design: This was a retrospective, multinational, multicenter observational study. Patients: Patients with IGHD (n = 107) were recruited. Interventions: All patients received GH treatment at replacement doses. The GHR genotype (fl-GHR/fl-GHR, fl-GHR/d3-GHR, or d3-GHR/d3-GHR) was determined by PCR amplification. Main Outcome Measures: Measures included height sd score, height velocity, height velocity sd score at baseline and 1 yr of GH treatment, and their changes. Results: There was no statistically significant difference of the main outcome measures between patients with the d3-GHR allele (n = 48) and patients who were homozygous for the fl-GHR allele (n = 59). Moreover, the genotype group did not contribute significantly to the growth prediction in multiple linear regression models. Conclusions: Our results indicate that the d3-GHR allele does not affect response to GH treatment or contribute to growth predictions in patients with IGHD who received replacement doses of GH aiming to restore a normal GH status. We did not confirm the previously reported data obtained in patients small for gestational age or with idiopathic short stature who received supraphysiological GH doses.

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Prevalence of children born small for gestational age with short stature who qualify for growth hormone treatment

Italian Journal of Pediatrics ◽

10.1186/s13052-021-01026-3 ◽

2021 ◽

Vol 47 (1) ◽

Author(s):

Gianluca Tamaro ◽

Mariagrazia Pizzul ◽

Giuliana Gaeta ◽

Raffaella Servello ◽

Marina Trevisan ◽

...

Keyword(s):

Growth Hormone ◽

Short Stature ◽

Gestational Age ◽

Small For Gestational Age ◽

Well Being ◽

Italian Population ◽

Gh Treatment ◽

Short Children ◽

Catch Up ◽

Rhgh Treatment

Abstract Background Recombinant human growth hormone (rhGH) is approved in Europe as a treatment for short children born small for gestational age (SGA) since 2003. However, no study evaluated the prevalence of SGA children with short stature who qualify for rhGH in Europe so far. This study aimed to investigate in an Italian population the prevalence of children born SGA, of short stature in children born SGA, and of SGA children who qualify for rhGH treatment at 4 years of age. Methods We conducted a population-based study on primary care pediatricians’ databases in Trieste, Italy. Data was collected on 3769 children born between 2004 and 2014. SGA was defined as birth weight and/or birth length ≤ − 2 SDS. Data on height and weight were registered at the closest well-being visit to 1, 2, 3, 4 years of age. Short stature was defined as height ≤ − 2 SDS. Short children born SGA who qualify for rhGH treatment were identified according to Note AIFA #39 criteria (age ≥ 4 years; height ≤ − 2.5 SDS; growth velocity < 50th percentile). Results Full data at birth were available for 3250 children. The SGA prevalence was 3.6% (0.8% SGA for weight, 2.2% SGA for length, 0.6% SGA for both weight and length). The prevalence of short stature among SGA children was 9% at 1 year of age, 6% at 2 years (significantly higher in preterm in the first 2 years), 4% at 3 years, 3% at 4 years (all born at term). At 4 years of age, median height SDS was − 0.52. One child born SGA was eligible for GH treatment (0.8% among SGA children). Conclusions The prevalence in a general pediatric population of children born SGA who qualify for GH treatment was 1:3250. Although the prevalence of SGA in our population was similar to previous studies, catch-up growth was recorded earlier in our sample compared to previous reports, and term babies had late catch-up. Height SDS of children born SGA at 4 years of age was lower than expected (− 0.52 SDS).

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