Kerac Marko, Bunn James, Seal Andrew, Thindwa Mariam, Tomkins Andrew, Sadler Kate, Bahwere Paluku, Collins Steve
Valid International, Oxford, UK.
Lancet. 2009 Jul 11;374(9684):136-44. doi: 10.1016/S0140-6736(09)60884-9.
Severe acute malnutrition affects 13 million children worldwide and causes 1-2 million deaths every year. Our aim was to assess the clinical and nutritional efficacy of a probiotic and prebiotic functional food for the treatment of severe acute malnutrition in a HIV-prevalent setting.
We recruited 795 Malawian children (age range 5 to 168 months [median 22, IQR 15 to 32]) from July 12, 2006, to March 7, 2007, into a double-blind, randomised, placebo-controlled efficacy trial. For generalisability, all admissions for severe acute malnutrition treatment were eligible for recruitment. After stabilisation with milk feeds, children were randomly assigned to ready-to-use therapeutic food either with (n=399) or without (n=396) Synbiotic2000 Forte. Average prescribed Synbiotic dose was 10(10) colony-forming units or more of lactic acid bacteria per day for the duration of treatment (median 33 days). Primary outcome was nutritional cure (weight-for-height >80% of National Center for Health Statistics median on two consecutive outpatient visits). Secondary outcomes included death, weight gain, time to cure, and prevalence of clinical symptoms (diarrhoea, fever, and respiratory problems). Analysis was on an intention-to-treat basis. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN19364765.
Nutritional cure was similar in both Synbiotic and control groups (53.9% [215 of 399] and 51.3% [203 of 396]; p=0.40). Secondary outcomes were also similar between groups. HIV seropositivity was associated with worse outcomes overall, but did not modify or confound the negative results. Subgroup analyses showed possible trends towards reduced outpatient mortality in the Synbiotic group (p=0.06).
In Malawi, Synbiotic2000 Forte did not improve severe acute malnutrition outcomes. The observation of reduced outpatient mortality might be caused by bias, confounding, or chance, but is biologically plausible, has potential for public health impact, and should be explored in future studies.
Department for International Development (DfID).
全球有1300万儿童受重度急性营养不良影响，每年导致100 - 200万人死亡。我们的目的是评估一种益生菌和益生元功能食品在艾滋病高发地区治疗重度急性营养不良的临床和营养效果。
从2006年7月12日至2007年3月7日，我们招募了795名马拉维儿童（年龄范围5至168个月[中位数22，四分位间距15至32]），进行一项双盲、随机、安慰剂对照的疗效试验。为确保普遍性，所有因重度急性营养不良入院治疗的儿童均符合招募条件。在用奶类喂养使其病情稳定后，将儿童随机分配至即食治疗食品组，其中一组（n = 399）添加Synbiotic2000 Forte，另一组（n = 396）不添加。治疗期间（中位数33天），Synbiotic的平均规定剂量为每天10(10)个菌落形成单位或更多的乳酸菌。主要结局为营养治愈（连续两次门诊就诊时身高别体重>美国国家卫生统计中心中位数的80%）。次要结局包括死亡、体重增加、治愈时间以及临床症状（腹泻、发热和呼吸问题）的发生率。分析采用意向性分析。该试验已注册为国际标准随机对照试验，编号为ISRCTN19364765。
Synbiotic组和对照组的营养治愈情况相似（分别为53.9%[399例中的215例]和51.3%[396例中的203例]；p = 0.40）。两组的次要结局也相似。总体而言，HIV血清阳性与更差的结局相关，但并未改变或混淆阴性结果。亚组分析显示，Synbiotic组门诊死亡率可能有降低趋势（p = 0.06）。
在马拉维，Synbiotic2000 Forte并未改善重度急性营养不良的结局。门诊死亡率降低这一观察结果可能是由偏倚、混杂因素或机遇导致，但从生物学角度来看是合理的，对公共卫生有潜在影响，应在未来研究中进一步探讨。
国际发展部（DfID）。
