Supplementary Material for: Hyperbaric Oxygen Therapy Is Beneficial for the Improvement of Clinical Symptoms of Cerebral Palsy: A Systematic Review and Meta-Analysis

<b><i>Introduction:</i></b> Hyperbaric oxygen (HBO) has been used for the treatment of cerebral palsy for more than 20 years, but its efficacy and safety are still controversial. In this systematic review and meta-analysis, we evaluated the currently promulgated data related to the efficacy of HBO for patients with cerebral palsy. <b><i>Methods:</i></b> We searched the PubMed/Medline, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases (from their inception to April 2020) for randomized controlled trials published in English or Chinese. Two researchers used the Cochrane Collaboration tool for data extraction and an independent quality assessment. The extracted data were analyzed by Review Manager 5.3 software. <b><i>Results:</i></b> A total of 25 studies consistent with the inclusion criteria were included, with a total of 2,146 people, which included 1,185 participants in the HBO group and 961 in the control group. This meta-analysis showed that when compared with the controls, HBO therapy can improve the gross motor functions evaluated by the Gross Motor Function Measure (<i>n</i> = 696, SMD 0.29, 95% CI [0.07–0.51], Z = 2.62, <i>p</i> = 0.009) and Gross Motor Function Classification System (<i>n</i> = 248, MD –0.40, 95% CI [–0.52 to –0.27], Z = 6.28, <i>p</i> &lt; 0.00001), global developmental level evaluated by Gesell (<i>n</i> = 560, RR 1.30, 95% CI [1.19–1.42], Z = 6.03, <i>p</i> &lt; 0.00001) and developmental quotient (<i>n</i> = 374, MD 8.25, 95% CI [6.48–10.01], Z = 9.15, <i>p</i> &lt; 0.00001) and language expression (<i>n</i> = 270, MD 4.34, 95% CI [2.30–6.38], Z = 4.17, <i>p</i> &lt; 0.00001) and comprehension (<i>n</i> = 270, MD 4.87, 95% CI [2.87–6.88], Z = 4.76, <i>p</i> &lt; 0.00001). HBO therapy only caused mild ear pain. However, the quality of the data for all outcomes evaluated by the Grading of Recommendations Assessment, Development, and Evaluation analysis was very low. <b><i>Conclusions:</i></b> HBO therapy may produce a much more efficient clinical experiment result than the control group with cerebral palsy patients, and HBO therapy is well tolerated and relatively safe for the included participants.

**引言：** 高压氧（Hyperbaric oxygen, HBO）用于治疗脑瘫已有二十余年历史，但其疗效与安全性仍存在广泛争议。本项系统评价与荟萃分析旨在评估当前已发布的、针对高压氧治疗脑瘫患者疗效的相关研究数据。

**方法：** 我们检索了PubMed/Medline、Embase、Web of Science、Cochrane图书馆、中国知网（China National Knowledge Infrastructure）及万方数据库（Wanfang），检索时限为各数据库自建库起至2020年4月，纳入语种为英文或中文的随机对照试验。由两名研究者采用Cochrane协作网工具开展数据提取与独立质量评价，提取的数据通过Review Manager 5.3软件进行统计分析。

**结果：** 最终共有25项符合纳入标准的研究被纳入本分析，累计纳入2146名受试者，其中高压氧组1185人，对照组961人。本次荟萃分析结果显示，与对照组相比，高压氧治疗可显著改善经粗大运动功能量表（Gross Motor Function Measure, GMFM）评估的粗大运动功能（n=696，标准化均数差SMD=0.29，95%置信区间CI[0.07, 0.51]，Z=2.62，p=0.009），以及经粗大运动功能分类系统（Gross Motor Function Classification System, GMFCS）评估的运动功能分级结果（n=248，均数差MD=-0.40，95%CI[-0.52, -0.27]，Z=6.28，p<0.00001）；同时可提升经格塞尔发育量表（Gesell）评估的整体发育水平（n=560，相对危险度RR=1.30，95%CI[1.19, 1.42]，Z=6.03，p<0.00001）、发育商（n=374，MD=8.25，95%CI[6.48, 10.01]，Z=9.15，p<0.00001），以及语言表达能力（n=270，MD=4.34，95%CI[2.30, 6.38]，Z=4.17，p<0.00001）与语言理解能力（n=270，MD=4.87，95%CI[2.87, 6.88]，Z=4.76，p<0.00001）。高压氧治疗仅会引发轻度耳部疼痛，但采用推荐分级、评估、制定与评价（Grading of Recommendations Assessment, Development and Evaluation, GRADE）工具对所有结局指标的研究质量进行评价后发现，其证据质量均为极低级别。

**结论：** 对于脑瘫患者而言，高压氧治疗的临床疗效优于对照组，且纳入受试者对高压氧治疗耐受性良好，安全性相对较高。