目的 系統(tǒng)歸納、分析兒童環(huán)境性腸道功能障礙（EED）臨床試驗的設計和評價的主要技術要素，通過標準化試驗設計，為不同試驗結果的比較提供一定的可行性。方法 采用文獻研究的方法，通過系統(tǒng)檢索2000-2020年發(fā)表在PubMed、Cochrane以及EMBASE數(shù)據(jù)庫，由2位研究者獨立按照文獻納入與排除標準篩選兒童EED的臨床隨機對照試驗文獻，對納入文獻的試驗設計與評價技術要素進行提取。結果 檢索出文獻634篇，最終納入16項研究。（1）試驗目的：以改善腸道功能障礙的生物標志物為主14篇（87.5%），其中6篇（37.5%）同時評價了改善生長發(fā)育遲緩效果。（2）試驗設計：全部文獻均采用了隨機對照試驗（RCT）的設計方法，其中3篇（18.75%）為整群隨機對照試驗；選擇安慰劑對照9篇（56.25%），雙盲試驗12篇（75.0%）。（3）受試人群：一般為生活在資源匱乏地區(qū)，長期暴露于衛(wèi)生條件不足和營養(yǎng)缺乏環(huán)境中的兒童。（4）干預措施：主要是藥物類（乳酸桿菌GG、利福昔明、美沙拉嗪、鋅、阿苯達唑、阿奇霉素、多種微量元素）9篇（56.25%），其次食物類（菜豆、黑眼豆、米糠）和環(huán)境衛(wèi)生條件干預各3篇（18.75%）。（5）療程：3 d~36個月。（6）有效性評價指標：主要是EED生物標志物14篇（87.5%）和生長發(fā)育指標6篇（37.5%）。其中，生物標志物主要包括尿乳果糖與甘露醇比值變化（L：M）9篇（56.25%），尿乳果糖的排泄率6篇（37.5%）；糞便髓過氧化物酶5篇（31.25%），糞便α-1抗胰蛋白酶、糞便新蝶呤各4篇（25.0%），糞便鈣衛(wèi)蛋白3篇（18.75%），糞便再生基因1β2篇（12.5%）。生長發(fā)育指標包括年齡別身長/身高的Z評分、身長/身高、體質量各5篇（31.25%），年齡別體質量2篇（12.5%）等。（7）試驗的質量控制：以EED生物標志物為評價指標的研究，均在中心實驗室進行統(tǒng)一檢測。結論 納入的文獻信息完善、質量較高，結果涵蓋了兒童EED臨床研究設計與評價的基本技術要素，對于EED臨床試驗設計與實施，具有重要的借鑒與參考價值。

Objective To systematically evaluate the design points of clinical trials of children with Environmental Enteric Dysfunction(EED), and to provide certain feasibility for comparison with different trail results through standardized trail design. Methods By using the method of literature research, PubMed, Cochrane and EMBASE databases from 2000 to 2020 were searched systematically. Two researchers independently screened the clinical randomized controlled trials (RCTs) of children's EED according to the inclusion and exclusion criteria, and extracted the elements of experimental design and evaluation of the included articles. Results A total of 634 literatures were retrieved and 16 studies were included. (1) The main purpose of the study was to improve the biomarkers of intestinal dysfunction in 14 articles (87.5%), of which 6 (37.5%) evaluated the effect of improving growth retardation. (2) Design randomized controlled trials were used in all the studies, including 3 cluster-randomized controlled trial (18.75%), 9 placebo-controlled trials (56.25%) and 12 double-blind trials (75.0%). (3) The subjects were generally children living in resource deficient areas and exposed to inadequate sanitation and nutrition for a long time. (4) The main intervention measures were drugs (Lactobacillus GG, rifaximin, mesalazine, zinc, albendazole, azithromycin, multiple micronutrients) in 9 articles (56.25%), followed by food (cowpea, Common Bean, rice bran) and environmental hygiene condition intervention (18.75%). (5) The course of treatment was 3 days to 36 months. (6) The main efficacy indicators of 14 studies (87.5%) were EED biomarkers and 6 (37.5%) were linear growth. Among them, 9 articles (56.25%) of urinary lactulose/mannitol ratio change (L:M), 6 (37.5%) of urinary lactulose excretion rate, 5 (31.25%) of fecal myeloperoxidase, 4 (25.0%) of fecal α-1 antitrypsin and 4 (25.0%) of fecal neopterin, 3 (18.75%) of fecal calprotectin and 2 (12.5%) of fecal regeneration gene were used to evaluate EED biomarkers. The evaluation of linear growth includes 5 articles (31.25%) used length for age z-scores, length/height, weight, and 2 articles (12.5%) used weight for age zscores. (7) The quality control of the experiment and the study of EED biomarkers as the evaluation index were all tested in the central laboratory. Conclusion The included literature information is perfect and of high quality. The results cover the basic elements of the design and evaluation of pediatric EED clinical research, which has important reference value for the design and implementation of EED clinical trials.

R969.4;R985