Supplementary Material for: Potential for Optimization of Growth Hormone Treatment in Children with Growth Hormone Deficiency, Small for Gestational Age, and Turner Syndrome in Germany: Data from the PATRO^® Children Study

<b><i>Introduction:</i></b> Growth hormone (GH) treatment in children with growth hormone deficiency (GHD), short children born small for gestational age (SGA), and Turner syndrome (TS) is well established. However, a variety of parameters are still under discussion to achieve optimal growth results and efficiency of GH use in real-world treatment. <b><i>Methods:</i></b> German GH-treatment naïve patients of the PATRO Children database were grouped according to their start of treatment into groups of 3 years from 2007 to 2018. Time trends in age, gender, GH dose, height standard deviation score (SDS), first-year growth response, and Index of Responsiveness (IoR) were investigated in children with GHD, short children born SGA, and TS starting GH treatment in the German patient population of the PATRO Children database from 2007 to 2018 to determine specific parameters for GH treatment optimization. <b><i>Results:</i></b> All patient groups started GH treatment at a relatively high chronological age (2007–2009: GHD 8.33 ± 3.19, SGA 7.32 ± 2.52, TS 8.65 ± 4.39) with a slight but not significant trend towards younger therapy start up to 2016–2018 (GHD 8.04 ± 3.36, SGA 6.67 ± 2.65, TS 7.85 ± 3.38). In the GHD and SGA groups, female patients were underrepresented compared to male patients (GHD 32.3%, SGA 43.6%) with no significant change over the 4 time periods. Patients with GHD started GH treatment at a low dose (0.026 mg/kg/day). In SGA and TS patients, GH therapy was started below the registered dose recommendation (30.0 μg/kg/day and 33.7 μg/kg/day, respectively). In the first year of treatment, the mean GH dose was increased moderately (GHD: 30.7, SGA: 35.7, TS: 40.8 μg/kg/day). There was no significant change of GH dosing over time from 2007 to 2018. The IoR was comparable between time-groups for all 3 diagnoses. <b><i>Discussion:</i></b> This study shows potential for improvement of GH treatment results in GHD, SGA, and TS patients in terms of early dose adjustment and younger age at the start of treatment. This is in accordance with important parameters used in prediction models.

<b><i>引言：</i></b> 针对生长激素缺乏症（Growth Hormone Deficiency, GHD）、小于胎龄儿（Small for Gestational Age, SGA）及特纳综合征（Turner Syndrome, TS）患儿的生长激素（Growth Hormone, GH）治疗，其临床应用已较为成熟。然而，在真实世界临床诊疗中，如何通过优化各类参数以获得最佳生长效果与生长激素使用效率，仍是有待探讨的议题。<b><i>方法：</i></b> 本研究将PATRO儿童数据库中未接受过生长激素治疗的德国患者，按其治疗起始时间以3年为周期划分为2007至2018年的多个队列；针对该数据库中2007至2018年起始生长激素治疗的生长激素缺乏症、小于胎龄儿及特纳综合征患儿，分析其年龄、性别、生长激素剂量、身高标准差评分（Height Standard Deviation Score, SDS）、第一年生长应答情况及应答指数（Index of Responsiveness, IoR）的时间趋势，以期明确优化生长激素治疗的特异性参数。<b><i>结果：</i></b> 所有患者队列的生长激素治疗起始实足年龄均偏高：2007-2009年队列中，生长激素缺乏症患儿为8.33 ± 3.19岁，小于胎龄儿为7.32 ± 2.52岁，特纳综合征患儿为8.65 ± 4.39岁；至2016-2018年队列，治疗起始年龄呈轻度降低趋势，但未达到统计学显著性（生长激素缺乏症患儿8.04 ± 3.36岁，小于胎龄儿6.67 ± 2.65岁，特纳综合征患儿7.85 ± 3.38岁）。生长激素缺乏症与小于胎龄儿队列中，女性患者占比低于男性患者（生长激素缺乏症队列32.3%，小于胎龄儿队列43.6%），且四个时间队列中该比例无显著变化。生长激素缺乏症患者的初始生长激素给药剂量较低（0.026 mg/kg/日）；小于胎龄儿与特纳综合征患者的初始给药剂量则低于获批推荐剂量（分别为30.0 μg/kg/日与33.7 μg/kg/日）。治疗第一年，患者的平均生长激素给药剂量均有适度提升（生长激素缺乏症队列：30.7 μg/kg/日，小于胎龄儿队列：35.7 μg/kg/日，特纳综合征队列：40.8 μg/kg/日）；2007至2018年间，给药剂量未出现显著的时间趋势变化。三种诊断队列的应答指数（IoR）在各时间队列间均无显著差异。<b><i>讨论：</i></b> 本研究表明，针对生长激素缺乏症、小于胎龄儿及特纳综合征患者，通过早期调整给药剂量、降低治疗起始年龄，有望改善生长激素治疗效果，这与预测模型中所采用的关键参数相一致。

搜集汇总

背景与挑战

背景概述

该数据集是德国PATRO儿童研究的一部分，聚焦于生长激素缺陷、小于胎龄儿和特纳综合征儿童患者的生长激素治疗优化潜力。通过分析2007年至2018年间的真实世界数据，发现患者开始治疗时年龄较大、剂量偏低且存在性别不平衡，但时间趋势变化不显著，提示可通过早期剂量调整和更早治疗启动来改善疗效。数据集包含相关补充材料，用于支持研究结论。