Lazzerini Marzia, Rubert Laura, Pani Paola
Unit for Health Services Research and International Health, WHO Collaborating Centre for Maternal and Child Health, Institutefor Maternal and Child Health, Trieste, Italy.
Cochrane Database Syst Rev. 2013 Jun 21(6):CD009584. doi: 10.1002/14651858.CD009584.pub2.
Moderate acute malnutrition, also called moderate wasting, affects around 10% of children under five years of age in low- and middle-income countries. There are different approaches to addressing malnutrition with prepared foods in these settings; for example, providing lipid-based nutrient supplements or blended foods, either a full daily dose or in a low dose as a complement to the usual diet. There is no definitive consensus on the most effective way to treat children with moderate acute malnutrition.
To evaluate the safety and effectiveness of different types of specially formulated foods for children with moderate acute malnutrition in low- and middle-income countries, and to assess whether foods complying or not complying with specific nutritional compositions, such as the WHO technical specifications, are safe and effective.
In October 2012, we searched CENTRAL, MEDLINE, LILACS, CINAHL, BIBLIOMAP, POPLINE, ZETOC, ICTRP, mRCT, and ClinicalTrials.gov. In August 2012, we searched Embase. We also searched the reference lists of relevant papers and contacted nutrition-related organisations and researchers in this field.
We planned to included any relevant randomised controlled trials (RCTs), controlled clinical trials (CCTs), controlled before-and-after studies (CBAs), and interrupted time series (ITS) that evaluated specially formulated foods for the treatment of moderate acute malnutrition in children aged between six months and five years in low- and middle-income countries.
Two authors assessed trial eligibility and risk of bias, and extracted and analysed the data. We summarised dichotomous outcomes using risk ratios (RR) and continuous outcomes using mean differences (MD) with 95% confidence intervals (CI). Where appropriate, we combined data in meta-analyses using the random-effects model and assessed heterogeneity. The quality of evidence was assessed using GRADE methods.
Eight randomised controlled trials, enrolling 10,037 children, met our inclusion criteria. Seven of the trials were conducted in Africa. In general, the included studies were at a low risk of bias. There may have been a risk of performance bias as trial participants were aware which intervention group they were in, but we did not consider this likely to have biased the outcome measurement. We were unable to assess the risk of reporting bias in half of the trials and two trials were at high risk of attrition bias. Any specially formulated food versus standard care - the provision of food increased the recovery rate by 29% (RR 1.29, 95% CI 1.20 to 1.38; 2152 children, two trials; moderate quality evidence), decreased the number dropping out by 70% (RR 0.30, 95% CI 0.22 to 0.39; 1974 children, one trial; moderate quality evidence), and improved weight-for-height (MD 0.20 z-score, 95% CI 0.03 to 0.37; 1546 children, two trials; moderate quality evidence). The reduction in mortality did not reach statistical significance (RR 0.44; 95% CI 0.14 to 1.36; 1974 children, one trial; low quality evidence). Lipid-based nutrient supplements versus any blended foods (dry food mixtures, without high lipid content), at full doses - there was no significant difference in mortality (RR 0.93, 95% CI 0.54 to 1.62; 6367 children, five trials; moderate quality evidence), progression to severe malnutrition (RR 0.88, 95% CI 0.72 to 1.07; 4537 children, three trials; high quality evidence), or the number of dropouts from the nutritional programme (RR 1.14, 95% CI 0.62 to 2.11; 5107 children, four trials; moderate quality evidence). However, lipid-based nutrient supplements significantly increased the number of children recovered (RR 1.10, 95% CI 1.04 to 1.16; 6367 children, five trials; moderate quality evidence), and decreased the number of non-recovering children (RR 0.53, 95% CI 0.40 to 0.69; 4537 children, three trials; high quality evidence). LNS also improved weight gain, weight-for-height, and mid-upper arm circumference, although for these outcomes, the improvement was modest (moderate quality evidence). One trial observed more children with vomiting in the lipid-based nutrient supplements group compared to those receiving blended food (RR 1.43, 95% CI 1.11 to 1.85; 2712 children, one trial; low quality evidence). Foods at complementary doses - no firm conclusion could be drawn on the comparisons between LNS at complementary dose and blended foods at complementary or full dose (low quality evidence). Lipid-based nutrient supplements versus specific types of blended foods - a recently developed enriched blended food (CSB++) resulted in similar outcomes to LNS (4758 children, three trials; moderate to high quality evidence). Different types of blended foods - in one trial, CSB++ did not show any significant benefit over locally made blended food, for example, Misola, in number who recovered, number who died, or weight gain (moderate to high quality evidence). Improved adequacy of home diet - no study evaluated the impact of improving adequacy of local diet, such as local foods prepared at home according to a given recipe or of home processing of local foods (soaking, germination, malting, fermentation) in order to increase their nutritional content.
AUTHORS' CONCLUSIONS: In conclusion, there is moderate to high quality evidence that both lipid-based nutrient supplements and blended foods are effective in treating children with MAM. Although lipid-based nutrient supplements (LNS) led to a clinically significant benefit in the number of children recovered in comparison with blended foods, LNS did not reduce mortality, the risk of default or progression to SAM. It also induced more vomiting. Blended foods such as CSB++ may be equally effective and cheaper than LNS. Most of the research so far has focused on industrialised foods, and on short-term outcomes of MAM. There are no studies evaluating interventions to improve the quality of the home diet, an approach that should be evaluated in settings where food is available, and nutritional education and habits are the main determinants of malnutrition. There are no studies from Asia, where moderate acute malnutrition is most prevalent.
中度急性营养不良，又称中度消瘦，影响着低收入和中等收入国家约10%的五岁以下儿童。在这些地区，有多种使用预制食品解决营养不良问题的方法；例如，提供基于脂质的营养补充剂或混合食品，既可以是全日剂量，也可以是低剂量作为日常饮食的补充。对于治疗中度急性营养不良儿童的最有效方法，目前尚无定论。
评估不同类型的特殊配方食品对低收入和中等收入国家中度急性营养不良儿童的安全性和有效性，并评估符合或不符合特定营养成分（如世卫组织技术规范）的食品是否安全有效。
2012年10月，我们检索了Cochrane系统评价数据库、医学期刊数据库、拉丁美洲和加勒比卫生科学数据库、护理学与健康领域数据库、文献地图数据库、人口在线数据库、ZETOC数据库、国际临床试验注册平台、mRCT数据库和临床试验.gov。2012年8月，我们检索了Embase。我们还检索了相关论文的参考文献列表，并联系了该领域的营养相关组织和研究人员。
我们计划纳入任何相关的随机对照试验（RCT）、对照临床试验（CCT）、前后对照研究（CBA）和中断时间序列（ITS），这些研究评估了特殊配方食品对低收入和中等收入国家6个月至5岁儿童中度急性营养不良的治疗效果。
两位作者评估了试验的 eligibility 和偏倚风险，并提取和分析了数据。我们使用风险比（RR）汇总二分法结果，使用平均差（MD）汇总连续结果，并给出95%置信区间（CI）。在适当情况下，我们使用随机效应模型在meta分析中合并数据，并评估异质性。使用GRADE方法评估证据质量。
八项随机对照试验，共纳入10,037名儿童，符合我们的纳入标准。其中七项试验在非洲进行。总体而言，纳入的研究偏倚风险较低。由于试验参与者知道自己所在的干预组可能存在实施偏倚风险，但我们认为这不太可能影响结果测量。我们无法评估一半试验中的报告偏倚风险，两项试验存在高失访偏倚风险。任何特殊配方食品与标准护理相比——提供食品使恢复率提高了29%（RR 1.29，95% CI 1.20至1.38；2152名儿童，两项试验；中等质量证据），退出人数减少了70%（RR 0.30，95% CI 0.22至0.39；1974名儿童，一项试验；中等质量证据），并改善了身高别体重（MD 0.20 z评分，95% CI 0.03至0.37；1546名儿童，两项试验；中等质量证据）。死亡率的降低未达到统计学意义（RR 0.44；95% CI 0.14至1.36；1974名儿童，一项试验；低质量证据）。全剂量的基于脂质的营养补充剂与任何混合食品（干食品混合物，无高脂肪含量）相比——死亡率无显著差异（RR 0.93，95% CI 0.54至1.62；6367名儿童,五项试验；中等质量证据），进展为重度营养不良的情况无显著差异（RR 0.88，95% CI 0.72至1.07；4537名儿童，三项试验；高质量证据），或营养计划中的退出人数无显著差异（RR 1.14，95% CI 0.62至2.11；5107名儿童，四项试验；中等质量证据）。然而，基于脂质的营养补充剂显著增加了恢复儿童的数量（RR 1.10，95% CI 1.04至1.16；6367名儿童，五项试验；中等质量证据），并减少了未恢复儿童的数量（RR 0.53，95% CI 0.40至0.69；4537名儿童，三项试验；高质量证据）。基于脂质的营养补充剂也改善了体重增加、身高别体重和上臂中部周长，尽管对于这些结果，改善程度较小（中等质量证据）。一项试验观察到，与接受混合食品的儿童相比，基于脂质的营养补充剂组中呕吐的儿童更多（RR 1.43，95% CI 1.11至1.85；2712名儿童，一项试验；低质量证据）。补充剂量的食品——关于补充剂量的基于脂质的营养补充剂与补充或全剂量的混合食品之间的比较，无法得出明确结论（低质量证据）。基于脂质的营养补充剂与特定类型的混合食品相比——一种最近开发的强化混合食品（CSB++）产生的结果与基于脂质的营养补充剂相似（4758名儿童，三项试验；中等至高质量证据）。不同类型的混合食品——在一项试验中，CSB++在恢复人数、死亡人数或体重增加方面，与当地制作的混合食品（如米索拉）相比，未显示出任何显著益处（中等至高质量证据）。改善家庭饮食的充足性——没有研究评估改善当地饮食充足性的影响，例如根据给定食谱在家中制作的当地食物，或对当地食物进行家庭加工（浸泡、发芽、麦芽化、发酵）以增加其营养成分。
总之，有中等至高质量的证据表明，基于脂质的营养补充剂和混合食品在治疗中度急性营养不良儿童方面都是有效的。尽管与混合食品相比，基于脂质的营养补充剂（LNS）在恢复儿童数量方面带来了临床上显著的益处，但LNS并未降低死亡率、违约风险或进展为重度急性营养不良的风险。它还引发了更多呕吐。混合食品如CSB++可能同样有效且比LNS更便宜。到目前为止，大多数研究都集中在工业化食品以及中度急性营养不良的短期结果上。没有研究评估改善家庭饮食质量的干预措施，在有食物供应且营养教育和习惯是营养不良主要决定因素的环境中，这种方法应该得到评估。没有来自亚洲的研究，而亚洲是中度急性营养不良最普遍的地区。
