Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children's Hospital of Fudan University, Shanghai, China.
Medical Affairs, GeneScience Pharmaceuticals Co., Ltd. (GenSci), Shanghai, China.
Endocrine. 2024 Dec;86(3):1121-1130. doi: 10.1007/s12020-024-04009-6. Epub 2024 Aug 29.
The study aimed to evaluate the factors influencing recombinant human growth hormone (rhGH) treatment in Chinese children with short stature born small for gestational age (SGA).
A single-centre, real-world retrospective study was conducted in short stature children born SGA in China. Outcomes were observed at 6, 12, 18, 24, 30, and 36 months. Outcome measures included height standard deviation score (HTSDS), height, growth velocity (GV), and change of HTSDS (ΔHTSDS). The study used the generalized estimating equation (GEE) to identify potential influencing factors, such as rhGH treatment duration, age at rhGH initiation, sex, 11p15 hypomethylation, GH secretion, and birth weight. A subgroup analysis was conducted to investigate the impact of 11p15 hypomethylation related to SGA or impaired GH secretion.
Of all 101 SGA patients included in the screening, 41 were eligible for inclusion in the study. The mean age at rhGH initiation was 5.6 ± 2.4 years. The results of the GEE analysis showed a significant association between time after rhGH initiation and HTSDS, height, GV, and ΔHTSDS. GV increased after treatment, with the highest increase observed in the first six months. Additionally, the study found negative correlations between 11p15 hypomethylation and GV, as well as between birth weight and both GV and ΔHTSDS. The study found a positive correlation between impairment in GH secretion and both GV and ΔHTSDS. No statistically significant difference was observed in the comparison of GV or ΔHTSDS between the initiation age of GH treatment and 11p15 hypomethylation. After 24 and 30 months of rhGH treatment, patients with impaired GH secretion had significantly higher ΔHTSDS scores.
In short stature Chinese children born SGA, those without SGA-related 11p15 hypomethylation or with impaired GH secretion showed better response to rhGH treatment. These findings highlight the importance of pre-treatment evaluation, including genetic and endocrine assessments.
本研究旨在评估影响中国胎龄小导致身材矮小（SGA）出生的儿童接受重组人生长激素（rhGH）治疗的因素。
在中国，对胎龄小导致身材矮小的儿童进行了一项单中心、真实世界的回顾性研究。在 6、12、18、24、30 和 36 个月时观察结局。结局指标包括身高标准差评分（HTSDS）、身高、生长速度（GV）和 HTSDS 变化（ΔHTSDS）。研究采用广义估计方程（GEE）来识别潜在的影响因素，如 rhGH 治疗持续时间、rhGH 起始年龄、性别、11p15 低甲基化、GH 分泌和出生体重。还进行了亚组分析，以探讨与 SGA 或 GH 分泌受损相关的 11p15 低甲基化的影响。
在所有 101 名符合筛选标准的 SGA 患者中，有 41 名符合纳入研究标准。rhGH 起始年龄的平均值为 5.6±2.4 岁。GEE 分析结果显示，rhGH 起始后时间与 HTSDS、身高、GV 和 ΔHTSDS 之间存在显著关联。治疗后 GV 增加，前六个月增加最明显。此外，该研究还发现 11p15 低甲基化与 GV 之间呈负相关，与出生体重与 GV 和 ΔHTSDS 之间也呈负相关。研究发现 GH 分泌受损与 GV 和 ΔHTSDS 之间呈正相关。GH 治疗起始年龄与 11p15 低甲基化之间在 GV 或 ΔHTSDS 的比较中未观察到统计学差异。rhGH 治疗 24 个月和 30 个月后，GH 分泌受损的患者 ΔHTSDS 评分显著更高。
在中国胎龄小导致身材矮小的儿童中，无 SGA 相关 11p15 低甲基化或 GH 分泌受损的患者对 rhGH 治疗的反应更好。这些发现强调了治疗前评估的重要性，包括遗传和内分泌评估。
