Proof-of-concept study of the efficacy of a microbiota-directed complementary food formulation (MDCF) for treating moderate acute malnutrition.

BACKGROUND: 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. METHODS: 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. DISCUSSION: 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. TRIAL REGISTRATION: The primary MAM and post-SAM MAM trials are registered in Clintrials.gov (NCT04015999 and NCT04015986, registered on July 11, 2019, retrospectively registered).

Outcomes of a food voucher program and factors associated with the recovery rate of children with moderate acute malnutrition in Far North Cameroon.

BACKGROUND: Research on moderate acute malnutrition (MAM) is limited, despite its high prevalence. This study examined outcomes of bi-weekly locally available foods provided via a food voucher program (FVP) on nutritional recovery [mid-upper arm circumference (MUAC) ≥ 125 mm] from MAM (defined as MUAC between 115 and 124 mm) and identified the factors associated with recovery rate in Kaélé health district, Far North Region of Cameroon. METHODS: This was a prospective study with 474 MAM children aged 6-59 months. Food voucher distribution and MUAC screening were conducted at 6 bi-weekly visits or until the child was recovered. Time to recovery was evaluated with multivariate Cox proportional regression hazard models with associations quantified using adjusted hazard ratio (aHR). The trend for MUAC, including its determinants, was examined with multivariate linear mixed effect models. RESULTS: The recovery rate was 78.3% by 6 weeks after the first food basket; 3.4% remained MAM, and 5.9% were transferred for treatment for severe acute malnutrition (SAM defined as MUAC < 115 mm). Boys were 34% more likely to recover from MAM than girls [aHR = 1.34, 95%CI (1.09, 1.67)]. Children aged 24-53 months were 30% more likely to recover than those aged 6-11 months [aHR = 1.30, 95%CI (0.99, 1.70)]. A one unit increase in weight-for-height Z-score (WHZ) was associated with 1.89-fold greater likelihood of recovery [aHR = 1.89, 95%CI (1.66, 2.14)]. Male children had on average 1.82 mm greater increase in MUAC than female children (p < 0.001). One unit increase in WHZ was associated with 3.42 mm increase in MUAC (p = 0.025). Children aged 12-23 and 24-53 months had 1.03 mm and 2.44 mm, respectively, greater increase in MUAC over the program than children aged 6-11 months (all p < 0.01). CONCLUSION: The recovery rate of MAM children treated with the FVP met the Sphere standards for targeted supplementary feeding programs (> 75%). Child's WHZ, gender and age were significant factors associated with MUAC increase and recovery from MAM in the FVP. These findings indicate the FVP approach shows promise as an effective alternative treatment for MAM with consideration of associated factors and merits further evaluation.

Filling the Gaps for Enhancing the Effectiveness of Community-Based Programs Combining Treatment and Prevention of Child Malnutrition: Results from the Rainbow Project 2015⁻17 in Zambia.

BACKGROUND: Child malnutrition, in all its forms, is a public health priority in Zambia. After implementations based on a previous evaluation in 2012⁻14 were made, the efficacy of the Rainbow Project Supplementary Feeding Programs (SFPs) for the integrated management of severe acute malnutrition (SAM), moderate acute malnutrition (MAM), and underweight was reassessed in 2015⁻17. METHODS: The outcomes were compared with International Standards and with those of 2012⁻14. Cox proportional risk regression analysis was performed to identify predictors of mortality and defaulting. RESULTS: The data for 900 under-five year-old malnourished children were analyzed. Rainbow's 2015⁻17 outcomes met International Standards, for total and also when stratified for different type of malnutrition. A better performance than 2012⁻14 was noted in the main areas previously identified as critical: mortality rates were halved (5.6% vs. 3.1%, p = 0.01); significant improvements in average weight gain and mean length of stay were registered for recovered children (p < 0.001). HIV infection (5.5; 1.9⁻15.9), WAZ <⁻3 (4.6; 1.3⁻16.1), and kwashiorkor (3.5; 1.2⁻9.5) remained the major predictors of mortality. Secondly, training community volunteers consistently increased the awareness of a child's HIV status (+30%; p < 0.001). CONCLUSION: Rainbow SFPs provide an integrated community-based approach for the treatment and prevention of child malnutrition in Zambia, with its effectiveness significantly enhanced after the gaps in activities were filled.

A Pilot Randomized Controlled Trial of a New Supplementary Food Designed to Enhance Cognitive Performance during Prevention and Treatment of Malnutrition in Childhood.

BACKGROUND: Cognitive impairment associated with childhood malnutrition and stunting is generally considered irreversible. OBJECTIVE: The aim was to test a new nutritional supplement for the prevention and treatment of moderate-acute malnutrition (MAM) focused on enhancing cognitive performance. METHODS: An 11-wk, village-randomized, controlled pilot trial was conducted in 78 children aged 1-3 or 5-7 y living in villages in Guinea-Bissau. The supplement contained 291 kcal/d for young children and 350 kcal/d for older children and included 5 nutrients and 2 flavan-3-ol-rich ingredients not present in current food-based recommendations for MAM. Local bakers prepared the supplement from a combination of locally sourced items and an imported mix of ingredients, and it was administered by community health workers 5 d/wk. The primary outcome was executive function abilities at 11 wk. Secondary outcomes included additional cognitive measures and changes in z scores for weight (weight-for-age) and height (height-for-age) and hemoglobin concentrations at 11 wk. An index of cerebral blood flow (CBF) was also measured at 11 wk to explore the use of this measurement as a biological index of cognitive impairment. RESULTS: There were no significant differences in any outcome between groups at baseline. There was a beneficial effect of random assignment to the supplement group on working memory at 11 wk in children aged 1-3 y (P < 0.05). This difference contrasted with no effect in older children and was not associated with faster growth rate. In addition, CBF correlated with task-switching performance (P < 0.05). CONCLUSIONS: These preliminary data suggest that cognitive impairment can be monitored with measurement of CBF. In addition, the findings provide preliminary data that suggest that it may be possible to improve poor cognitive performance in young children through changes in the nutritional formulation of supplementary foods used to prevent and treat MAM. Powered studies of the new supplement formulation are needed. This trial was registered at clinicaltrials.gov as NCT03017209.

Intestinal helminth infections and nutritional status of children attending primary schools in Wakiso District, Central Uganda.

A cross-sectional study to assess the prevalence of intestinal helminth infections and nutritional status of primary school children was conducted in the Wakiso district in Central Uganda. A total of 432 primary school children aged 6-14 years were randomly selected from 23 schools. Anthropometric measurements of weight, height, MUAC were undertaken and analyzed using AnthroPlus software. Stool samples were examined using a Kato-Katz method. The prevalence of stunting, underweight and moderate acute malnutrition (MAM) was 22.5%, 5.3% and 18.5% respectively. Males had a threefold risk of being underweight (OR 3.2, 95% CI 1.17-9.4, p = 0.011) and 2 fold risk of suffering from MAM (OR 2.1, 95% CI 1.21-3.48, p = 0.004). Children aged 10-14 years had a 2.9 fold risk of stunting (OR 2.9, 95% CI 1.37-6.16, p = 0.002) and 1.9 risk of MAM (OR 1.9, 95% CI 1.07-3.44, p = 0.019). Attending urban slum schools had 1.7 fold risk of stunting (OR 1.7, 95% CI 1.03-2.75, p = 0.027). Rural schools presented a twofold risk of helminth infection (OR 1.95, 95% CI 1.12-3.32, p = 0.012). The prevalence of helminth infections was (10.9%), (3.1%), (1.9%), (0.2%) for hookworm, Trichuriatrichiura, Schistosomamansoni and Ascarislumbricoides, respectively. The study revealed that 26.6%, 46% and 10.3% of incidences of stunting, underweight and MAM respectively were attributable to helminth infections.