Pediatric Endocrinology, Indiana University School of Medicine, Indianapolis, Indiana 46202.
Endocrinology, Lilly Research Laboratories, Windlesham, Surrey GU20 6PH, United Kingdom.
J Clin Endocrinol Metab. 2017 Sep 1;102(9):3195-3205. doi: 10.1210/jc.2017-00214.
Although pediatric growth hormone (GH) treatment is generally considered safe for approved indications, concerns have been raised regarding potential for increased risk of mortality in adults treated with GH during childhood.
To assess mortality in children receiving GH.
Prospective, multinational, observational study.
Eight hundred twenty-seven study sites in 30 countries.
Children with growth disorders.
GH treatment during childhood.
Standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) using age- and sex-specific rates from the general population.
Among 9504 GH-treated patients followed for ≥4 years (67,163 person-years of follow-up), 42 deaths were reported (SMR, 0.77; 95% CI, 0.56 to 1.05). SMR was significantly elevated in patients with history of malignant neoplasia (6.97; 95% CI, 3.81 to 11.69) and borderline elevated for those with other serious non-GH-deficient conditions (2.47; 95% CI, 0.99-5.09). SMRs were not elevated for children with history of benign neoplasia (1.44; 95% CI, 0.17 to 5.20), idiopathic GHD (0.11; 95% CI, 0.02 to 0.33), idiopathic short stature (0.20; 95% CI, 0.01 to 1.10), short stature associated with small for gestational age (SGA) birth (0.66; 95% CI, 0.08 to 2.37), Turner syndrome (0.51; 95% CI, 0.06 to 1.83), or short stature homeobox-containing (SHOX) gene deficiency (0.83; 95% CI, 0.02 to 4.65).
No significant increases in mortality were observed for GH-treated children with idiopathic GHD, idiopathic short stature, born SGA, Turner syndrome, SHOX deficiency, or history of benign neoplasia. Mortality was elevated for children with prior malignancy and those with underlying serious non-GH-deficient medical conditions.
尽管儿科生长激素（GH）治疗通常被认为对批准的适应症是安全的，但人们对儿童期接受 GH 治疗的成年人潜在死亡风险增加表示担忧。
评估接受 GH 治疗的儿童的死亡率。
前瞻性、多国、观察性研究。
30 个国家的 827 个研究地点。
患有生长障碍的儿童。
儿童时期的 GH 治疗。
使用一般人群的年龄和性别特异性死亡率计算标准化死亡率比（SMR）和 95%置信区间（CI）。
在 9504 名接受 GH 治疗且随访时间≥4 年的患者（67163 人年随访）中，报告了 42 例死亡（SMR，0.77；95%CI，0.56 至 1.05）。有恶性肿瘤病史的患者的 SMR 显著升高（6.97；95%CI，3.81 至 11.69），其他严重非 GH 缺乏症的患者的 SMR 边缘升高（2.47；95%CI，0.99 至 5.09）。有良性肿瘤病史的儿童的 SMR 无升高（1.44；95%CI，0.17 至 5.20），特发性 GHD（0.11；95%CI，0.02 至 0.33），特发性身材矮小（0.20；95%CI，0.01 至 1.10），与出生体重不足（SGA）相关的身材矮小（0.66；95%CI，0.08 至 2.37），特纳综合征（0.51；95%CI，0.06 至 1.83），或短身材同源盒基因（SHOX）缺陷（0.83；95%CI，0.02 至 4.65）。
特发性 GHD、特发性身材矮小、出生 SGA、特纳综合征、SHOX 缺乏或良性肿瘤病史的 GH 治疗儿童未观察到死亡率显著增加。既往有恶性肿瘤和其他严重非 GH 缺乏基础医学疾病的儿童死亡率升高。
