He Mengyang, Deng Xiangling, Wang Xuan, Wan Yuxiang, Huang Jinchang, Zhang Zhixin, Niu Wenquan
Graduate School, Beijing University of Chinese Medicine, Beijing, China.
Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, China.
Front Pediatr. 2022 Apr 22;10:866295. doi: 10.3389/fped.2022.866295. eCollection 2022.
The safety of recombinant human growth hormone (rhGH) treatment in childhood and the role of rhGH therapy in promoting tumorigenesis and progression have been the subject of debate for decades. We aimed to systematically assess the relationship between rhGH therapy in children and adolescents and clinical outcomes, including all-cause mortality, cancer mortality, cancer incidence, and risk of the second neoplasm.
Literature retrieval, study selection, and data extraction were completed independently and in duplicate. Effect-size estimates are expressed as standardized mortality ratios (SMRs), standardized incidence ratio (SIR), and relative risk (RR) with a 95% CI.
Data from 24 articles, involving 254,776 persons, were meta-analyzed. Overall analyses revealed the association of rhGH therapy was not statistically significant with all-cause mortality (SMR = 1.28; 95% CI: 0.58-2.84; = 0.547; = 99.2%; Tau = 2.154) and cancer mortality (SMR = 2.59; 95% CI: 0.55-12.09; = 0.228; = 96.7%; Tau = 2.361) and also cancer incidence (SIR = 1.54; 95% CI: 0.68-3.47; = 0.229; = 97.5%; Tau = 2.287), yet statistical significance was observed for second neoplasm (RR = 1.77; 95% CI: 1.33-2.35; = 0.001; = 26.7%; Tau = 0.055). Differences in the geographic region, gender, treatment duration, mean rhGH dose, overall rhGH exposure dose, and initial disease accounted for heterogeneity in the subgroup analyses.
Our findings indicate that the rhGH therapy is not related to all-cause mortality and cancer mortality and cancer incidence, yet it seems to trigger a second tumor risk. Future prospective studies are needed to confirm our findings and answer the more challenging question regarding the optimal dose of rhGH therapy in children and adolescents.
重组人生长激素（rhGH）治疗儿童的安全性以及rhGH治疗在促进肿瘤发生和进展中的作用，数十年来一直是争论的焦点。我们旨在系统评估儿童和青少年rhGH治疗与临床结局之间的关系，包括全因死亡率、癌症死亡率、癌症发病率以及第二肿瘤的风险。
文献检索、研究选择和数据提取由两人独立完成且重复进行。效应量估计值以标准化死亡率比（SMR）、标准化发病率比（SIR）和相对风险（RR）表示，并伴有95%置信区间。
对24篇文章的数据进行荟萃分析，涉及254,776人。总体分析显示，rhGH治疗与全因死亡率（SMR = 1.28；95%置信区间：0.58 - 2.84；P = 0.547；I² = 99.2%；Tau = 2.154）、癌症死亡率（SMR = 2.59；95%置信区间：0.55 - 12.09；P = 0.228；I² = 96.7%；Tau = 2.361）以及癌症发病率（SIR = 1.54；95%置信区间：0.68 - 3.47；P = 0.229；I² = 97.5%；Tau = 2.287）之间的关联无统计学意义，但第二肿瘤有统计学意义（RR = 1.77；95%置信区间：1.33 - 2.35；P = 0.001；I² = 26.7%；Tau = 0.055）。地理区域、性别、治疗持续时间、平均rhGH剂量、rhGH总暴露剂量和初始疾病的差异在亚组分析中导致了异质性。
我们的研究结果表明，rhGH治疗与全因死亡率、癌症死亡率和癌症发病率无关，但似乎会引发第二肿瘤风险。未来需要进行前瞻性研究以证实我们的发现，并回答关于儿童和青少年rhGH治疗最佳剂量这一更具挑战性的问题。
