de Zegher F, Butenandt O, Chatelain P, Albertsson-Wikland K, Jonsson B, Löfström A, Chaussain J L
Department of Pediatrics, University of Leuven, Belgium.
Acta Paediatr Suppl. 1997 Nov;423:207-12. doi: 10.1111/j.1651-2227.1997.tb18418.x.
A minority of children born small for gestational age (SGA) fail to achieve sufficient catch-up growth during infancy and remain short throughout childhood, apparently without being growth hormone (GH) deficient. A previous metanalysis of four trials revealed that GH treatment over a period of 2 years induced a dose-dependent acceleration of linear growth and, to a lesser extent, of the rate of bone maturation in short, prepubertal children born SGA. The rate of bone maturation and the change in height SDS for bone age from the previous 2-year metanalysis have been re-analysed according to chronological age (two prepubertal age groups: group A, 3.0-5.9 years old; group B, 6.0-8.9 years old). The rate of bone maturation was slower in younger than in older prepubertal children; this difference was more marked in children receiving high-dose (0.2 or 0.3 IU/kg/day) GH treatment (p < or = 0.01). Accordingly, the change in height SDS for bone age was increased by high-dose GH treatment in both age groups (p < or = 0.01), and was more pronounced in younger than in older children (1.45 +/- 0.28 versus 0.63 +/- 0.20; p < or = 0.01). Height SDS data from 100 short, prepubertal children born SGA have been analysed over 4 years. The change in height SDS appeared to be related to the average dose of GH. A mean GH dose of 0.1 IU/kg/day over 4 years was administered either as 0.1 IU/kg/day for 4 years (continuous) or as 0.2 IU/kg/day for 2 years, followed by 2 years without GH treatment (discontinuous). After 4 years of treatment, the increase in height SDS for the continuous and discontinuous treatment schedules was similar, being 1.42 +/- 0.10 SDS and 1.58 +/- 0.17 SDS, respectively. In a second regimen, a mean GH dose of 0.2 IU/kg/day over 3 years was administered either as 0.2 IU/kg/day for 3 years (continuous) or as 0.3 IU/kg/day for 2 years, followed by 1 year without GH treatment (discontinuous). After 3 years, the increase in height SDS with the continuous and discontinuous treatment schedules was similar, being 2.01 +/- 0.18 SDS and 2.22 +/- 0.16 SDS, respectively. GH administration was well tolerated in all treatment groups. In conclusion, the rate of bone maturation in short, prepubertal children born SGA treated with GH appeared to depend not only on the dose of GH, but also on the age of the child. GH treatment resulted in a prolonged increase in height SDS, the magnitude of the rise being dependent on the average GH dose rather than on the continuous or discontinuous mode of GH administration.
一小部分小于胎龄儿（SGA）出生的儿童在婴儿期未能实现足够的追赶生长，并且在整个儿童期都保持矮小，显然不存在生长激素（GH）缺乏。先前对四项试验的荟萃分析显示，在2年期间进行GH治疗可诱导矮小的青春期前SGA出生儿童线性生长呈剂量依赖性加速，在较小程度上也可加速骨成熟速率。根据实际年龄（两个青春期前年龄组：A组，3.0 - 5.9岁；B组，6.0 - 8.9岁），对先前2年荟萃分析中的骨成熟速率和骨龄身高标准差评分（SDS）变化进行了重新分析。青春期前较年幼儿童的骨成熟速率比年龄较大儿童慢；这种差异在接受高剂量（0.2或0.3 IU/kg/天）GH治疗的儿童中更为明显（p≤0.01）。因此，两个年龄组中高剂量GH治疗均使骨龄身高SDS增加（p≤0.01），且在较年幼儿童中比年龄较大儿童更显著（1.45± 0.28对0.63±0.20；p≤0.01）。对100名矮小的青春期前SGA出生儿童的身高SDS数据进行了4年的分析。身高SDS的变化似乎与GH的平均剂量有关。4年期间平均GH剂量为0.1 IU/kg/天，给药方式为4年中每天0.1 IU/kg（连续）或2年中每天0.2 IU/kg，随后2年不进行GH治疗（间断）。治疗4年后，连续和间断治疗方案的身高SDS增加相似，分别为1.42±0.10 SDS和1.58±0.17 SDS。在第二种方案中，3年期间平均GH剂量为0.2 IU/kg/天，给药方式为3年中每天0.2 IU/kg（连续）或2年中每天0.3 IU/kg，随后1年不进行GH治疗（间断）。3年后，连续和间断治疗方案的身高SDS增加相似，分别为2.01±0.18 SDS和2.22±0.16 SDS。所有治疗组对GH给药耐受性良好。总之，接受GH治疗的矮小青春期前SGA出生儿童的骨成熟速率似乎不仅取决于GH剂量，还取决于儿童的年龄。GH治疗导致身高SDS持续增加，增加幅度取决于GH平均剂量而非GH给药的连续或间断方式。
