重组人生长激素治疗小于胎龄矮小儿童的疗效和安全性

The therapeutic effect and safety of recombinant human growth hormone in short children born small for ges-tational age

目的 研究重组人生长激素对小于胎龄（SGA）矮小儿童的治疗作用和安全性。 方法 共有22例SGA矮小儿童纳入研究，按随机数字表法分为重组人生长激素治疗低剂量组[0.1 IU/（kg·d）]和高剂量组[0.2 IU/（kg·d）]。治疗前、治疗中及治疗2年后分别测定身高、体质量、骨龄、胰岛素样生长因子-1（IGF-1）、胰岛素样生长因子结合蛋白3（IGFBP-3），并计算生长速度、身高标准差积分（HtSDS），利用B-P法预测成年后终身高。测定空腹及餐后血糖、胰岛素、促甲状腺激素、T3、T4及糖化血红蛋白水平。 结果 SGA的生长激素基础值为（2.94±3.27） μg/L。高剂量组在治疗2年后，生长速率[（8.11±1.31） cm/年]、身高标准差（－1.16±0.83）及预测成年身高[（163.68±6.76） cm]均高于治疗前[（4.21±0.99） cm/年、－3.00±0.71、（156.54±7.39） cm]，差异均有统计学意义（F＝110.30、30.47、26.20，P均〈0.01）。低剂量组在治疗后2年，生长速率、身高标准差、骨龄均显著高于治疗前（P均〈0.05），预测成年身高的差异无统计学意义（P〉0.05）。高低剂量2组在治疗后2年，IGF-1、IGFBP-3高于治疗前。高剂量组在治疗后2年，相比较于治疗前，IGF-1的增加值与生长速率、身高标准差及预测成年身高的增加值均呈正相关（r＝0.567 4、0.652 4、0.584 3、0.499 8，P均〈0.05）。低剂量组与治疗前比较，IGF-1的增加值与生长速率、身高标准差的增加值均呈正相关（r＝0.437 1、0.405 6、0.501 1，P均〈0.05），但与预测成年身高增加值无相关性（r＝0.200 8，P〉0.05）。2组治疗后2年，与治疗前相比，空腹和餐后血糖、胰岛素、促甲状腺激素、T3、T4及糖化血红蛋白等无异常改变（P均〉0.05）。 结论 0.2 IU/（kg·d）的重组人生长激素可以显著提高SGA矮小儿童的生长速率和预测成年身高，是治疗SGA矮小的有效、安全的策略。

Objective To study the therapeutic effect and safety of recombinant human growth hormone in short children born small for gestational age （SGA）. Methods Twenty - two short children born SGA were randomly divided into 2 groups and were exposed to different doses of recombinant human growth hormone, which were low dose group [0.1 IU/（ kg · d） ] and high dose group [0.2 IU/（ kg · d） ]. Treatment was carried out for 2 years. Before and after treatment, height, weight, bone age, insulin - like growth factor 1 （ IGF - 1 ）, insulin - like growth factor - binding protein 3 （ IGFBP - 3 ）, growth rate （ GV）, height standard deviation scores （ HtSDS）, predicted adult lifetime height （PAH） ,fasting and postprandial blood glucose, insulin, thyroid stimulating hormone （TSH）, T3, T4, and glycosylated hemoglobin were measured. Results Basic value of growth hormone in SGA infant was （2.94 ± 3.27） μg/L. Two years after treatment of growth hormone in high dose group, growth rate [ （8.11 ± 1.31 ） cm/year vs （4.21 ± 0.99 ）cm/ year] ,HtSDS（ -1.16 ±0.83 vs -3.00 ±0.71） ,and PAH[ （163.68 ±6.76） cm vs （156.54 ±7.39） cm] were sig- nificantly higher than those before treatment（ F = 110.3,30.47,26.20, all P 〈 0.01 ）. Similar changes were observed in low dose group except for PAH. In high dose group after 2 years of treatment, IGF - 1, IGFBP - 3 were significantly higher than those before the treatment and the difference was statistically significant（ all P 〈 0.05）. Although the plas- ma levels of IGF - 1 and IGFBP - 3 in low dose group in 2 years of treatment were significantly higher than those before the treatment ,the difference was not statistically significant（ P 〉 0.05 ）. Compared with that before treatment ,the added value of IGF - 1 had a positive correlation with the added values of growth rate, HtSDS and PAH （ r = 0.567 4,0. 652 4, 0. 584 3,0. 499 8, all P 〈 0.05 ）. Similar observations were found in low dose group （ r = 0. 437 1,0. 405 6 and 0.501 1 ,all P 〈 0.05 ）. However,the added value of IGF- 1 in low dose group had no correlation with PAH （r = 0. 200 8 ,P 〉 0.05 ）. Compared with that before treatment ,2 groups had no differences in fasting and postprandial blood glucose,insulin,TSH,T3, T4 and glycosylated hemoglobin （ all P 〉 0.05 ）. Conclusions Recombinant human growth hormone [ 0.20 IU/（ kg · d） ] may significantly increase the growth rate and PAH of short children born SGA,which is a safe and effective strategy for the treatment of short SGA.