Short children born small for gestational age: hormonal regulation of growth
Abstract
It is generally recognized that children born small for gestational age (SGA) have a higher risk of short stature than children born at normal size. It has been suggested that the programming of the endocrine axes occurs during critical phases of fetal development and is affected by intrauterine growth retardation. The main objectives of this thesis were to study the hormonal regulation of growth in prepubertal children born SGA who did not show complete postnatal catch-up growth and to evaluate the efficacy and tolerability of growth hormone (GH) treatment.The study group included 177 children with a birth weight and/or birth length below -2 standard deviation score (SDS) compared with Swedish reference values corrected for gestational age. All of the children were still short at/or after 2 years of age, and were prepubertal and short at the time of the investigation. Fourteen children with dysmorphic features of Silver-Russell syndrome were included in the study group. Prepubertal healthy children born appropriate for gestational age (AGA) of both short or normal stature were used as reference groups.The mean estimated GH secretion rate was lower in the children born SGA compared with the reference groups born AGA, of either short or normal stature. Moreover, in the youngest children born SGA (2-6 years of age) a different pattern of GH secretion was found, with a high basal GH level, low peak amplitude, and high peak frequency. The majority of the children born SGA had pretreatment levels of GH-binding protein (GHBP) within the range previously reported for normal children. However, levels of insulin-like growth factor-I (IGF-I), IGF-binding protein-3 (IGFBP-3) and leptin were significantly reduced compared with the reference values. In contrast, cortisol and insulin levels were not different to those in normal children born AGA of either normal or short stature.GH treatment for at least 2 years revealed a dose-dependent increase in the growth rate; mean height was normalized within 3 years of GH treatment. GH treatment was well tolerated and no side effects were observed. Up to 76% of the variability of the growth response could be explained by different prediction models: the best predictors were the dose of GH, the spontaneous GH secretion rate, chronological age at the start of treatment, maternal height SDS, basal leptin levels, and the short-term changes in the ratio of IGF-I/IGFBP-3 during treatment, in this order of importance. Mean GHBP levels increased by 27% after 1 year of therapy, despite the high degree of variability in the individual GHBP response to treatment. IGF-I levels increased significantly during the first year of treatment, whereas IGFBP-3 levels increased mainly during the first 10 days of therapy. A dose-dependent increase in insulin levels was observed after 2 years of treatment without negative consequences on glucose or glycosylated haemoglobin. In contrast, leptin levels decreased during the GH treatment period. In conclusion, the low spontaneous GH secretion rate and a disturbed GH secretion pattern, together with low serum levels of IGF-I, IGFBP-3 and leptin, might contribute to the reduced postnatal growth in the subgroup of children born SGA who remain short during childhood. These children may benefit from GH treatment. Finally, fasting insulin concentrations and cortisol levels were normal in short children born SGA.Key words: small for gestational age, intrauterine growth retardation, short stature, growth hormone, growth hormone-binding protein, insulin-like growth factor-I, insulin-like growth factor-binding protein-3, leptin, cortisol, insulin.
University
Göteborgs universitet/University of Gothenburg
Institution
Department of Pediatrics
Avdelningen för pediatrik / International Pediatric Growth Research Centre
Date of defence
1997-10-02
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Date
1997Author
Boguszewski, Margaret C.S. 1964-
Keywords
Intrauterine growth retardation
short stature
growth hormone
growth hormene-binding protein
insulin-like grwth factor-I
insulin-like growth factor-binding protein-
Publication type
Doctoral thesis
Metadata
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