Nutrition and Clinical Services Division (NCSD), International Centre for Diarrhoeal Disease Research, Bangladesh (icddr, b), 68, Shaheed Tajuddin Ahmed Sarani Mohakhali, Dhaka, 1212, Bangladesh.
The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA.
BMC Public Health. 2020 Feb 17;20(1):242. doi: 10.1186/s12889-020-8330-8.
Childhood undernutrition remains a significant global health challenge accounting for over half of all under 5 child mortality. Moderate acute malnutrition (MAM), which leads to wasting [weight-for-length z-scores (WLZ) between - 2 and - 3], affects 33 million children under 5 globally and more than 2 million in Bangladesh alone. We have previously reported that acute malnutrition in this population is associated with gut microbiota immaturity, and in a small, 1-month pre-proof-of-concept (POC) study demonstrated that a microbiota-directed complementary food formulation (MDCF-2) was able to repair this immaturity, promote weight gain and increase plasma biomarkers and mediators of healthy growth. Here we describe the design controlled feeding study that tests whether MDCF-2 exhibits superior efficacy (ponderal growth, host biomarkers of a biological state) than a conventional Ready-to-use Supplementary Food (RUSF) in children with MAM over intervention period of 3 months.
Two separate cohorts of 12-18-month-old children will be enrolled: 124 with primary MAM, and 124 with MAM after having been treated for severe acute malnutrition (post-SAM MAM). We have established several field sites in an urban slum located in the Mirpur district of Dhaka, Bangladesh and at a rural site, Kurigram in the north of Bangladesh. The two groups of children receiving MDCF-2 and RUSF will be compared at baseline (pre-intervention), after 1 month, at the end of intervention (3 months), 1 month after cessation of intervention, and every 6 months thereafter for 4 years.
This study will determine whether daily, controlled administration of MDCF-2 for 3 months provides superior improvements in weight gain, microbiota repair, and elevated levels of key plasma biomarkers/mediators of healthy growth compared to the control RUSF formulation. The pathogenesis of MAM is poorly defined and there are currently no WHO-approved treatments; results from the current study of children with primary MAM and post-SAM MAM will shed light on the effects of the gut microbiota on childhood growth/development and will provide a knowledge base that may help improve complementary feeding practices.
The primary MAM and post-SAM MAM trials are registered in Clintrials.gov (NCT04015999 and NCT04015986, registered on July 11, 2019, retrospectively registered).
儿童期营养不良仍然是一个重大的全球健康挑战，占五岁以下儿童死亡人数的一半以上。中度急性营养不良（MAM）导致消瘦[体重长度 z 分数（WLZ）在-2 至-3 之间]，影响全球 3300 万五岁以下儿童，仅孟加拉国就有 200 多万儿童受到影响。我们之前报告过，该人群中的急性营养不良与肠道微生物组不成熟有关，并且在一项小型的、为期 1 个月的预概念验证（POC）研究中表明，一种微生物组导向的补充食品配方（MDCF-2）能够修复这种不成熟，促进体重增加，并增加血浆生物标志物和健康生长的介质。在这里，我们描述了一项设计对照喂养研究，该研究旨在测试 MDCF-2 是否比传统的即食补充食品（RUSF）在干预期为 3 个月的 MAM 儿童中表现出更好的疗效（体重增长，宿主生物学状态的生物标志物）。
将招募两个独立的 12-18 个月大的儿童队列：124 名患有原发性 MAM 的儿童，以及 124 名患有严重急性营养不良（SAM 后）的儿童。我们已经在孟加拉国达卡的米尔普尔区的一个城市贫民窟和孟加拉国北部的库里格拉姆建立了几个实地站点。接受 MDCF-2 和 RUSF 的两组儿童将在基线（干预前）、干预 1 个月后、干预结束时（3 个月）、干预停止后 1 个月以及此后每 6 个月进行比较，共 4 年。
这项研究将确定每天控制 MDCF-2 的使用是否可以在 3 个月内提供更好的体重增长、微生物组修复和关键血浆生物标志物/健康生长介质水平的提高，与对照 RUSF 配方相比。MAM 的发病机制尚未明确，目前尚无世界卫生组织批准的治疗方法；目前对原发性 MAM 和 SAM 后 MAM 儿童的研究结果将阐明肠道微生物组对儿童生长/发育的影响，并为改善补充喂养实践提供知识基础。
原发性 MAM 和 SAM 后 MAM 试验在 Clintrials.gov 注册（NCT04015999 和 NCT04015986，于 2019 年 7 月 11 日注册，回顾性注册）。
