Children born small for gestational age may demonstrate continued growth retardation, resulting in persistent short stature. In the majority of the cases, this is linked with abnormal growth hormone secretion and also abnormal insulin-like growth factor levels. This review discusses the treatment of such children with recombinant human growth hormone. It illustrates the importance of starting therapy early, the dose-dependent response, and the advantages of continuous therapy and describes safety considerations.
"As there is an increased prevalence of metabolic disorders in later life among subjects who were born SGA, monitoring of glucose homeostasis is recommended in children born SGA who are treated with r-hGH [Chatelain et al. 2007]. Although alterations in insulin sensitivity have been observed after long-term GH therapy in short children born SGA, no adverse effects on glucose levels are thought to occur [Sas, 2001; Hokken- Koelega et al. 2004; Cutfield et al. 2006; Chatelain et al. 2007]. In our study, insulin resistance was not significantly changed from baseline in children born SGA, or after 4 weeks of r-hGH treatment in those born SGA relative to those born AGA, suggesting that short-term GH therapy did not lead to changes in glucose metabolism. "
[Show abstract][Hide abstract] ABSTRACT: To compare the response between Chinese children with growth hormone deficiency (GHD) born either small for gestational age (SGA) or appropriate for gestational age (AGA) after 4 weeks of recombinant human growth hormone (r-hGH) therapy.
This was a phase IV, open-label, multicenter, interventional study (NCT01187550). Prepubertal children with GHD received open-label treatment with daily r-hGH (0.033 mg/kg) for 4 weeks. Serum levels of insulin-like growth factor I (IGF-I) and insulin-like growth factor-binding protein 3 (IGFBP3), and metabolic markers (including fasting glucose, insulin, total cholesterol, and homeostasis model assessment of insulin resistance) were assessed at baseline and after 4 weeks of treatment, and were analyzed according to patient subgroup (SGA or AGA).
A total of 205 children with GHD (mean age 10.4 years; 175 AGA, 30 SGA) were included in the analysis. Mean baseline serum IGF-I and IGFBP3 standard deviation scores (SDS) across the whole patient population were lower than the population norms (mean values: -2.1 SDS for IGF-I and -1.2 SDS for IGFBP3), with no significant differences between the two patient subgroups. After 4 weeks, IGF-I and IGFBP3 levels increased by 1.0 SDS (p < 0.001) and 0.34 SDS (p < 0.001), respectively, but no significant differences were found between the two patient subgroups for growth-related or metabolic markers.
For children with GHD born SGA, IGF-I and IGFBP3 are short-term biomarkers of responsiveness to treatment with growth hormone, as for children with GHD born AGA.
Therapeutic advances in endocrinology and metabolism 04/2013; 4(2):41-9. DOI:10.1177/2042018813484051
"Effectiveness of GH treatment in short-statured children born SGA has been well demonstrated [12,13,42,43]. A 4-year study of GH treatment in SGA and GHD children enrolled in the NordiNet® international outcome study (IOS) demonstrated similar height improvement in SGA and GHD children, supporting the idea that GH treatment in non-GHD patients is as effective as it is in GHD children . "
[Show abstract][Hide abstract] ABSTRACT: Approximately 10% of children born small for their gestational age (SGA) fail to show catch-up growth and may remain short-statured as adults. Despite treatment guidelines for children born SGA that recommend referral for growth hormone (GH) therapy evaluation and initiation by ages 2 to 4 years, the average age of GH treatment initiation is typically much later, at ages 7 to 9 years. Delayed referral for GH treatment is problematic as studies show younger age at GH treatment initiation in children born SGA is an independent predictor for responses such as optimal growth acceleration, normalization of prepubertal height, and most importantly, adult height (AH). This review discusses the importance and associated challenges of early diagnosis of children born SGA who fail to show catch-up growth, contrasts the recommended age of referral for these patients and the average age of GH treatment initiation, and discusses studies showing the significant positive effects of early referral and treatment with GH on AHs in short-statured children born SGA. To optimize the eventual height in short-statured SGA children who fail to manifest catch-up growth, a lowering of the average age of referral for GH therapy evaluation is needed to better align with consensus recommendations for SGA management. The importance of increasing parental and physician awareness that most children born SGA will do well developmentally and will optimally benefit from early initiation of GH treatment when short-statured is addressed, as is the need to shift the age of referral to better align with consensus recommendations.
International Journal of Pediatric Endocrinology 05/2012; 2012(1):11. DOI:10.1186/1687-9856-2012-11
"GH treatment does not appear to be associated with an increased risk of malignancy . It is recommended that IGF-1 concentrations should be monitored and GH dose should be reduced in children with a plasma IGF-1 above +2 SD [58,59]. "
[Show abstract][Hide abstract] ABSTRACT: Children born small for gestational age (SGA) experience higher rates of morbidity and mortality than those born appropriate for gestational age. In Latin America, identification and optimal management of children born SGA is a critical issue. Leading experts in pediatric endocrinology throughout Latin America established working groups in order to discuss key challenges regarding the evaluation and management of children born SGA and ultimately develop a consensus statement.
SGA is defined as a birth weight and/or birth length greater than 2 standard deviations (SD) below the population reference mean for gestational age. SGA refers to body size and implies length-weight reference data in a geographical population whose ethnicity is known and specific to this group. Ideally, each country/region within Latin America should establish its own standards and make relevant updates. SGA children should be evaluated with standardized measures by trained personnel every 3 months during year 1 and every 6 months during year 2. Those without catch-up growth within the first 6 months of life need further evaluation, as do children whose weight is ≤ -2 SD at age 2 years. Growth hormone treatment can begin in SGA children > 2 years with short stature (< -2.0 SD) and a growth velocity < 25th percentile for their age, and should continue until final height (a growth velocity below 2 cm/year or a bone age of > 14 years for girls and > 16 years for boys) is reached. Blood glucose, thyroid function, HbA1c, and insulin-like growth factor-1 (IGF-1) should be monitored once a year. Monitoring insulin changes from baseline and surrogates of insulin sensitivity is essential. Reduced fetal growth followed by excessive postnatal catch-up in height, and particularly in weight, should be closely monitored. In both sexes, gonadal function should be monitored especially during puberty.
Children born SGA should be carefully followed by a multidisciplinary group that includes perinatologists, pediatricians, nutritionists, and pediatric endocrinologists since 10% to 15% will continue to have weight and height deficiency through development and may benefit from growth hormone treatment. Standards/guidelines should be developed on a country/region basis throughout Latin America.
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