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儿童期起病的炎症性肠病所致生长障碍的激素治疗:一项采用试验序贯分析的系统评价和荟萃分析

Hormonal therapy for impaired growth due to pediatric-onset inflammatory bowel disease: a systematic review and meta-analysis with trial sequential analysis.

作者信息

Melo Mardhen Catunda Rocha, Lima Rian Vilar, Strada Maryana Modena, Rocha João Lucas Maia, Cavalcante Beatriz Vieira, Bezerra Maria Lya Pinheiro, Martins Lívia Vasconcelos, Torquato Maria Clara Parente, Veloso Túlio Veras, Macedo Delanie Bulcao

机构信息

Department of Medicine, University of Fortaleza, Fortaleza, Ceará, Brazil.

Endocrinology Division, Emilio Ribas Medicina Diagnóstica, Fortaleza, Ceará, Brazil.

出版信息

J Pediatr Endocrinol Metab. 2025 Apr 8;38(6):562-569. doi: 10.1515/jpem-2024-0609. Print 2025 Jun 26.

Abstract

INTRODUCTION

Inflammatory bowel diseases (IBDs) have an increasing incidence in the pediatric population. The dysabsorptive effects of this condition often lead to a decrease in linear growth. However, the effectiveness and safety of growth hormone (GH) therapy in this population is still a topic of debate, with studies showing conflicting results.

CONTENT

MEDLINE, Embase, and Cochrane Library databases were systematically searched according to the PRISMA guidelines. All experimental studies featuring children with IBD receiving GH therapy were included. In addition, a trial sequential analysis (TSA) was conducted to determine the sample size required for each outcome. The prospective registry was carried out under protocol CRD42024563079. The total data set comprised eight studies involving 127 patients with IBD, 78 (61.41 %) of whom received GH therapy, with a mean follow-up duration of 1.3 years. A statistically significant effect of GH was found in increasing the height standard deviation score (HtSDS) of children with IBD (standardized mean difference - SMD=1.07; CI=0.58, 1.56; p<0.0001). When comparing children who received GH with controls, no significant improvement in HtSDS was observed (SMD=0.18; CI=-0.73, 1.08; p=0.70). However, meta-regression analysis indicated that a longer follow-up was associated with a greater improvement in the HtSDS (p=0.04). Regarding height velocity (HV), a significant increase was found when comparing measurements before and after the initiation of hormone therapy (mean difference - MD=4.09; CI=2.58, 5.60; p<0.0001). An increase in HV was also noted in children receiving GH compared to the control group (MD=4.47; CI=2.03, 6.90; p=0.0003). No significant changes in the Pediatric Crohn's Disease Activity Index (PCDAI) were detected, comparing values before and after the start of treatment (MD=-10.09; CI=-22.29, 2.10; p=0.10). The overall prevalence of any adverse effect was estimated at 15.51 % (95 % CI: 2.32-58.70 %). Most common reaction was itching at injection sites. TSA indicated a low risk of overestimating or underestimating the intervention's effect on the analyzed outcomes.

SUMMARY

Our study points to the effectiveness and safety of GH therapy in children with IBD and growth impairment.

OUTLOOK

Further randomized controlled trials (RCT) with standardized methodologies and extended follow-up periods are necessary to confirm these findings.

摘要

引言

炎症性肠病(IBD)在儿科人群中的发病率呈上升趋势。这种疾病的吸收不良效应常常导致线性生长减缓。然而,生长激素(GH)治疗在该人群中的有效性和安全性仍是一个有争议的话题,各项研究结果相互矛盾。

内容

根据PRISMA指南,系统检索了MEDLINE、Embase和Cochrane图书馆数据库。纳入了所有以接受GH治疗的IBD儿童为研究对象的实验性研究。此外,进行了一项试验序贯分析(TSA)以确定每个结局所需的样本量。前瞻性注册研究按照方案CRD42024563079进行。数据集总共包括八项研究,涉及127例IBD患者,其中78例(61.41%)接受了GH治疗,平均随访时间为1.3年。研究发现,GH对提高IBD儿童的身高标准差评分(HtSDS)有统计学显著效果(标准化均数差-SMD = 1.07;可信区间CI = 0.58, 1.56;p < 0.0001)。将接受GH治疗的儿童与对照组儿童进行比较时,未观察到HtSDS有显著改善(SMD = 0.18;CI = -0.73, 1.08;p = 0.70)。然而,meta回归分析表明,随访时间越长,HtSDS改善越大(p = 0.04)。关于身高增长速度(HV),比较激素治疗开始前后的测量值时发现有显著增加(平均差-MD = 4.09;CI = 2.58, 5.60;p < 0.0001)。与对照组相比,接受GH治疗的儿童的HV也有所增加(MD = 4.47;CI = 2.03, 6.90;p = 0.0003)。比较治疗开始前后的小儿克罗恩病活动指数(PCDAI)值,未发现有显著变化(MD = -10.09;CI = -22.29, 2.10;p = 0.10)。任何不良反应的总体发生率估计为15.51%(95%CI:2.32 - 58.70%)。最常见的反应是注射部位瘙痒。TSA表明高估或低估干预措施对分析结局影响的风险较低。

总结

我们的研究表明GH治疗对IBD和生长发育受损儿童具有有效性和安全性。

展望

需要进一步开展方法标准化且随访期延长的随机对照试验(RCT)来证实这些发现。

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