Availability, use, and consumption practices of ready-to-use therapeutic foods prescribed to children with uncomplicated severe acute malnutrition aged 6-59 months during outpatient treatment in Burkina Faso.

Ready-to-use-therapeutic-foods (RUTF) was designed for the nutritional management of children with uncomplicated severe acute malnutrition (SAM) treated as outpatients. However, to our knowledge, no study has evaluated the availability, use and consumption of RUTF within the beneficiary household in programs and in the context of a reduction in the dose of RUTF. This study, assessed the effect of a reduction in RUTF dose on the availability, use, consumption, and perceptions of caregivers on RUTF prescribed to 516 children treated for SAM, aged 6-59 months in Burkina Faso. Children received a weekly dose of RUTF according to their treatment arm until recovery. Data were collected by structured individual in-depth interviews, with caregivers one month and two months post-admission. Differences between children receiving reduced RUTF (intervention arm) and those receiving standard RUTF (control arm) were assessed by Poisson, logistic, and ordered logistic regression model. RUTF was available for the whole week in 95% in intervention arm compared to about 98% in control arm (p > 0.05). Starting from week 3 onwards, children in intervention arm consumed an average of 9 sachets of RUTF per week compared to 15 sachets in control arm (p < 0.001) and 5% of children in intervention arm reported leftover compared to 11% in control arm (p < 0.05). About 40% of children in intervention arm consumed RUTF at least 3-times per day compared to 82% in control arm (p < 0.001). The amount of RUTF prescribed was perceived as sufficient in 93% by caregivers in intervention arm against 97% in control arm (p > 0.05). In conclusion, reducing the dose of RUTF did not affect the availability of RUTF during treatment but did reduce leftover and the frequency of consumption of RUTF.

Economic evaluation of a reduced dosage of ready-to-use therapeutic foods to treat uncomplicated severe acute malnourished children aged 6-59 months in Burkina Faso.

Ready-to-use therapeutic foods (RUTF) used to treat children with severe acute malnutrition (SAM) are costly, and the prescribed dosage has not been optimized. The MANGO trial, implemented by Action Contre la Faim in Burkina Faso, proved the non-inferiority of a reduced RUTF dosage in community-based treatment of uncomplicated SAM. We performed a cost-minimization analysis to assess the economic impact of transitioning from the standard to the reduced RUTF dose. We used a decision-analytic model to simulate a cohort of 399 children/arm, aged 6-59 months and receiving SAM treatment. We adopted a societal perspective: direct medical costs (drugs, materials and staff time), non-medical costs (caregiver expenses) and indirect costs (productivity loss) in 2017 international US dollar were included. Data were collected through interviews with 35 caregivers and 20 informants selected through deliberate sampling and the review trial financial documents. The overall treatment cost for 399 children/arm was $36,550 with the standard and $30,411 with the reduced dose, leading to $6,140 (16.8%) in cost savings ($15.43 saved/child treated). The cost/consultation was $11.6 and $9.6 in the standard and reduced arms, respectively, with RUTF accounting for 56.2% and 47.0% of the total. The savings/child treated was $11.4 in a scenario simulating the Burkinabè routine SAM treatment outside clinical trial settings. The reduced RUTF dose tested in the MANGO trial resulted in significant cost savings for SAM treatment. These results are useful for decision makers to estimate potential economic gains from an optimized SAM treatment protocol in Burkina Faso and similar contexts.

Critical evaluation of the appetite test for children with severe acute malnutrition.

OBJECTIVES: The appetite test is used to risk stratify for children with severe acute malnutrition (SAM) in inpatient or outpatient care. The test is recommended in guidelines despite lack of evidence. We evaluated its ability to identify children at risk of a poor treatment outcome. METHODS: We conducted an observational study of children diagnosed with SAM at three health facilities in Ethiopia. The appetite test was done independently, and the result did not affect decisions about hospitalisation and clinical care. Data were analysed using mixed linear and logistic regression models. RESULTS: Appetite was tested in 298 (89%) of 334 children enrolled; 56 (19%) passed. Children failing the appetite test had a 6.6% higher weight gain per day (95% CI: 2.6, 10.8) adjusted for type of treatment, oedema, duration of follow-up and age than children passing the test. We found medical complications in 179 (54%) children. Medical complications were associated with blood markers of metabolic disturbance. Children with medical complications tended to have lower weight gain than those without complications (3.5%, 95% CI: -0.25, 7.0). Neither the appetite test nor medical complications were correlated with bacteraemia or treatment failure. CONCLUSIONS: Our findings question the use of the appetite test to identify children who need inpatient care. An assessment of medical complications alone could be a useful risk indicator but needs to be evaluated in other settings.

OBJECTIF: Le test de l'appétit est utilisé pour stratifier les risques chez les enfants souffrant de malnutrition aiguë sévère (MAS) en soins hospitaliers ou ambulatoires. Le test est recommandé dans les directives malgré le manque d'évidence. Nous avons évalué sa capacité à identifier les enfants à risque de mauvais résultats de traitement. MÉTHODES: Nous avons mené une étude observationnelle chez des enfants diagnostiqués avec une MAS dans trois établissements de santé en Ethiopie. Le test de l'appétit a été effectué indépendamment et le résultat n'a pas affecté les décisions d'hospitalisation et de soins cliniques. Les données ont été analysées à l'aide de modèles de régression linéaire et logistique mixtes. RÉSULTATS: : L'appétit a été testé chez 298 (89%) des 334 enfants inscrits; 56 (19%) ont réussi le test. Les enfants qui échouaient au test de l'appétit avaient un gain de poids de 6,6% plus élevé par jour (IC95%: 2,6 à 10,8) ajusté pour le type de traitement, l'œdème, la durée du suivi et l'âge que les enfants réussissant le test. Nous avons trouvé des complications médicales chez 179 (54%) enfants. Des complications médicales ont été associées à des marqueurs sanguins de troubles métaboliques. Les enfants souffrant de complications médicales avaient tendance à avoir un gain de poids plus faible que ceux sans complications (3,5% ; IC95%: -0,25 à 7,0). Ni le test de l'appétit ni les complications médicales ne corrélaient avec une bactériémie ou à un échec du traitement CONCLUSION: Nos résultats remettent en question l'utilisation du test de l'appétit pour identifier les enfants qui ont besoin de soins hospitaliers. Une évaluation des complications médicales à elle seule pourrait être un indicateur de risque utile, mais doit être évaluée dans d'autres contextes MOTS-CLÉS: malnutrition aiguë sévère, appétit, gestionnaire de communauté, évaluation des risques, aliments thérapeutiques.

Nutrition rehabilitation of children with severe acute malnutrition: Revisiting studies undertaken by the National Institute of Nutrition.

Severe acute malnutrition (SAM) in children under five years is an important public health problem due to associated high mortality and long-term health consequences. Research on the dietary causes of SAM, especially the role and relative importance of dietary protein, in the aetiology of oedematous malnutrition, has led to considerable debates and controversies. The present article revisits some of the debates in this field, where the researchers at the National Institute of Nutrition (NIN), Hyderabad, India, with their pioneering work, have contributed to the global literature on the various facets of the disease. Highlighting the importance of energy as a bigger problem than protein malnutrition is a noteworthy contribution of NIN's research. It is, however, important to examine the protein quality of the diets in light of the new information on the lysine requirements. The article argues that the currently dominating hypothesis of free radical theory requires a critical review of the supporting evidence. Over the past few decades, the research has focused on low-cost diets using locally available foods. The article also argues that solutions based on local foods, being acceptable and sustainable, need to be strengthened for their effective delivery through the existing nutrition programmes. Recent evidence shows that the use of ready-to-use therapeutic foods (RUTF) with high micronutrient density may be linked with higher mortality possibly due to the high iron content, which could be counterproductive. There are several unaddressed concerns regarding the potential long-term impact of consumption of RUTF in children with SAM. More evidence and a cautious approach are, therefore, needed before implementing these solutions.

Challenges and opportunities of integration of community based Management of Acute Malnutrition into the government health system in Bangladesh: a qualitative study.

BACKGROUND: Severe acute malnutrition (SAM) in children is the most serious form of malnutrition and is associated with very high rates of morbidity and mortality. For sustainable SAM management, United Nations recommends integration of community based management of acute malnutrition (CMAM) into the health system. The objective of the study was to assess the preparedness of the health system to implement CMAM in Bangladesh. METHODS: The assessment was undertaken during January to May 2014 by conducting document review, key informant interviews, and direct observation. A total of 38 key informant interviews were conducted among government policy makers and program managers (n = 4), nutrition experts (n = 2), health and nutrition implementing partners (n = 2), development partner (n = 1), government health system staff (n = 5), government front line field workers (n = 22), and community members (n = 2). The assessment was based on: workforce, service delivery, financing, governance, information system, medical supplies, and the broad socio-political context. RESULTS: The government of Bangladesh has developed inpatient and outpatient guidelines for the management of SAM. There are cadres of community health workers of government and non-government actors who can be adequately trained to conduct CMAM. Inpatient management of SAM is available in 288 facilities across the country. However, only 2.7% doctors and 3.3% auxiliary staff are trained on facility based management of SAM. In functional facilities, uninterrupted supply of medicines and therapeutic diet are not available. There is resistance and disagreement among nutrition stakeholders regarding import or local production of ready-to-use therapeutic food (RUTF). Nutrition coordination is fragile and there is no functional supra-ministerial coordination platform for multi-sectoral and multi-stakeholder nutrition. CONCLUSION: There is an enabling environment for CMAM intervention in Bangladesh although health system strengthening is needed considering the barriers that have been identified. Training of facility based health staff, government community workers, and ensuring uninterrupted supply of medicines and logistics to the functional facilities should be the immediate priorities. Availability of ready-to-use therapeutic food (RUTF) is a critical component of CMAM and government should promote in-country production of RUTF for effective integration of CMAM into the health system in Bangladesh.

Local versus offshore production of ready-to-use therapeutic foods and small quantity lipid-based nutrient supplements.

Manufacturers on four continents currently produce ready-to-use therapeutic foods (RUTF). Some produce locally, near their intended users, while others produce offshore and ship their product long distances. Small quantity lipid-based nutrient supplements (SQ-LNS) such as Nutriset's Enov'Nutributter are not yet in widespread production. There has been speculation whether RUTF and SQ-LNS should be produced primarily offshore, locally, or both. We analyzed The United Nations Children's Fund (UNICEF) Supply Division data, reviewed published literature, and interviewed local manufacturers to identify key benefits and challenges to local versus offshore manufacture of RUTF. Both prices and estimated costs for locally produced product have consistently been higher than offshore prices. Local manufacture faces challenges in taxation on imported ingredients, low factory utilization, high interest rates, long cash conversion cycle, and less convenient access to quality testing labs. Benefits to local economies are not likely to be significant. Although offshore manufacturers offer RUTF at lower cost, local production is getting closer to cost parity for RUTF. UNICEF, which buys the majority of RUTF globally, continues to support local production, and efforts are underway to narrow the cost gap further. Expansion of RUTF producers into the production of other ready-to-use foods, including SQ-LNS in order to reach a larger market and achieve a more sustainable scale, may further close the cost and price gap. Local production of both RUTF and SQ-LNS could be encouraged by a favorable tax environment, assistance in lending, consistent forecasts from buyers, investment in reliable input supply chains, and local laboratory testing.

Ready-to-Use Supplementary Foods and Ready-to-Use Therapeutic Foods: Developing Product Standards.

The purpose of this commentary is to describe the current regulatory environment for the multitude of ready-to-use supplementary foods and ready-to-use therapeutic foods used in international feeding programs for undernourished and malnourished children. A perspective on the role of standards, their desirable scope, benefits and limitations as well as possible future developments of products in these categories also is provided.

Optimizing Ready-to-Use Therapeutic Foods for Protein Quality, Cost, and Acceptability.

This article describes current research on the development of alternative ready-to-use therapeutic foods (RUTFs) in the treatment of severe acute malnutrition. An innovative and versatile linear programming tool has been developed to facilitate the creation of therapeutic formulas that are determined acceptable on multiple levels: costs, ingredient acceptability, availability and stability, nutrient requirements, and personal preferences. The formulas are analyzed for ease of production by Washington University team members and for organoleptic properties acceptability to target populations. In the future, RUTF products that are cost-effective, acceptable, sustainable, and widely available will become a reality.

Perspective on alternative therapeutic feeds to treat severe acute malnutrition in children aged between 6 and 59 months in sub-Saharan Africa: a narrative review.

Worldwide, nearly 200 million children younger than 5 years old suffer from stunting and wasting, 2 different types of undernutrition. Moreover, 45% of deaths among children in that age group are associated with these conditions. Severe acute malnutrition (SAM) refers to children with a weight-for-height z score < -3, a midupper arm circumference < 115 mm, or the presence of bilateral edema, and is especially prevalent in low- and middle-income countries. Undernutrition in children can have a major impact on both their physical and cognitive development. It can lead to infections and death if it remains undetected or untreated. The use of therapeutic feeds is an important component in the management of SAM, which remains a challenge in poorly resourced countries. The aim of this review was to assess the alternatives to the standard therapeutic foods used to treat SAM and to summarize their advantages and disadvantages, providing an overview of current research. A literature search was performed from September to November 2022 using PubMed, the Trip medical database, and the German Institute for Medical Documentation and Information (DIMDI). This review includes 13 randomized controlled trials testing alternatives to the standard therapeutic foods used to treat SAM by using alternative ingredients or a reduced dosage. The results show that, while a few alternative ready-to-use therapeutic food formulas lead to recovery rates similar to those seen with the standard protocol, many alternatives were less effective in the affected children. Thus, the evidence is not yet strong enough to change the World Health Organization's guidelines. The review identifies promising results of treatment alternatives related to treatment outcomes and costs. Additional research should focus on the interventions that positively impact the recovery process of severely malnourished children to facilitate the treatment and enable greater treatment coverage worldwide.

The recent WHO guideline on acute malnutrition overestimates therapeutic energy requirement.

The World Health Organization has recently updated the guideline on the prevention and management of wasting and nutritional oedema (acute malnutrition) in infants and children under 5 years. Apart from differences with regard to the nutritional framework that defines the quantity of energy required as Ready-to-Use Therapeutic Food (RUTF) for the outpatient treatment of severe wasting and/or nutritional oedema, there are also important gaps in the practical guidance. Instead of the recommended energy intake of 150-185 kcal/kg/day, our alternative calculations indicate the requirement to be only 105-120 kcal/kg/day. If true, the implementation of such caloric overfeeding can have adverse consequences. Gaps in practical guidance also need to be addressed, including the timing of transition to home-based diets, maximal duration of therapeutic feeding, especially in non-responders (∼50% in South Asia), and the role of augmented home foods as the primary therapeutic food option.

Developmental and Nutritional Changes in Children with Severe Acute Malnutrition Provided with n-3 Fatty Acids Improved Ready-to-Use Therapeutic Food and Psychosocial Support: A Pilot Study in Tanzania.

Children with severe acute malnutrition (SAM) are at high risk of impaired development. Contributing causes include the inadequate intake of specific nutrients such as polyunsaturated fatty acids (PUFAs) and a lack of adequate stimulation. We conducted a pilot study assessing developmental and nutritional changes in children with SAM provided with a modified ready-to-use therapeutic food and context-specific psychosocial intervention in Mwanza, Tanzania. We recruited 82 children with SAM (6-36 months) and 88 sex- and age-matched non-malnourished children. We measured child development, using the Malawi Development Assessment Tool (MDAT), measures of family and maternal care for children, and whole-blood PUFA levels. At baseline, the mean total MDAT z-score of children with SAM was lower than non-malnourished children; -2.37 (95% confidence interval: -2.92; -1.82), as were their total n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) levels. After 8 weeks of intervention, MDAT z-scores improved in all domains, especially fine motor, among children with SAM. Total n-3 and EPA levels increased, total n-6 fatty acids decreased, and DHA remained unchanged. Family and maternal care also improved. The suggested benefits of the combined interventions on the developmental and nutritional status of children with SAM will be tested in a future trial.

A microbiota-directed complementary food intervention in 12-18-month-old Bangladeshi children improves linear growth.

BACKGROUND: Globally, stunting affects ∼150 million children under five, while wasting affects nearly 50 million. Current interventions have had limited effectiveness in ameliorating long-term sequelae of undernutrition including stunting, cognitive deficits and immune dysfunction. Disrupted development of the gut microbiota has been linked to the pathogenesis of undernutrition, providing potentially new treatment approaches. METHODS: 124 Bangladeshi children with moderate acute malnutrition (MAM) enrolled (at 12-18 months) in a previously reported 3-month RCT of a microbiota-directed complementary food (MDCF-2) were followed for two years. Weight and length were monitored by anthropometry, the abundances of bacterial strains were assessed by quantifying metagenome-assembled genomes (MAGs) in serially collected fecal samples and levels of growth-associated proteins were measured in plasma. FINDINGS: Children who had received MDCF-2 were significantly less stunted during follow-up than those who received a standard ready-to-use supplementary food (RUSF) [linear mixed-effects model, ßtreatment group x study week (95% CI) = 0.002 (0.001, 0.003); P = 0.004]. They also had elevated fecal abundances of Agathobacter faecis, Blautia massiliensis, Lachnospira and Dialister, plus increased levels of a group of 37 plasma proteins (linear model; FDR-adjusted P < 0.1), including IGF-1, neurotrophin receptor NTRK2 and multiple proteins linked to musculoskeletal and CNS development, that persisted for 6-months post-intervention. INTERPRETATION: MDCF-2 treatment of Bangladeshi children with MAM, which produced significant improvements in wasting during intervention, also reduced stunting during follow-up. These results suggest that the effectiveness of supplementary foods for undernutrition may be improved by including ingredients that sponsor healthy microbiota-host co-development. FUNDING: This work was supported by the BMGF (Grants OPP1134649/INV-000247).

Severe Acute Malnutrition: The Potential of Non-Peanut, Non-Milk Ready-to-Use Therapeutic Foods.

PURPOSE OF REVIEW: This review provides information on the prospect and effectiveness of ready-to-use therapeutic foods (RUTFs) produced locally without the addition of milk and peanut. RECENT FINDINGS: The foods used in fighting malnutrition in the past decades contributed little to the success of the alleviation program due to their non-effectiveness. Hence, RUTFs are introduced to fight malnutrition. The peanut allergies, the high cost of milk, and the high production cost of peanut RUTF have made its distribution, treatment spread, and accessibility very slow, especially in areas where it is highly needed. There is a need, therefore, for a low-cost RUTF that is acceptable and effective in treating severe acute malnutrition among under-5 children. This review shows both the success and failure of reported studies on the use of non-peanut and non-milk RUTF, including their cost of production as compared to the standard milk and peanut-based RUTF. It was hypothesised that replacing the milk ingredient component with legumes like soybeans can reduce the cost of production of RUTFs while also delivering an effective product in managing and treating severe acute malnutrition (SAM). Consumers generally accept them better because of their familiarity with the raw materials.

Ready-to-Use Therapeutic Foods (RUTFs) Based on Local Recipes Are as Efficacious and Have a Higher Acceptability than a Standard Peanut-Based RUTF: A Randomized Controlled Trial in Indonesia.

To strengthen community-based treatment of severe acute malnutrition (SAM) in Indonesia, locally produced ready-to-use therapeutic foods (RUTFs) are needed, but data on their acceptability and effectiveness are lacking. We conducted an individually randomized controlled trial in 302 children (6-59 months old) with uncomplicated SAM receiving 8 weeks of a standard RUTF (CON) or one of four alternative RUTFs produced with locally available ingredients: soybean (SOY), mungbean (MUN1, MUN2) or peanuts (PEA). The main outcomes were weight gain and product acceptability. Children consumed on average 2.2 kg of standard RUTF, but up to 4.5 kg of the local products (MUN2, p < 0.05). Mean weight gain did not differ across the groups (p > 0.05). Controlled for consumption, children receiving either CON or SOY RUTF gained >2 g/kg body weight (BW)/day compared with 1.6 g/kg BW/day in children receiving the other RUTF products (p > 0.05). Overall drop-out was 29.1%, ranging from 21.3% (MUN2) to 38.3% (CON, p > 0.05). Mean time to drop out was 19 days in the CON group, significantly shorter than in the PEA group (33.6 days, p < 0.05). Thus, with no difference in weight gain and better acceptance, the development of locally produced RUTFs in Indonesia is warranted to strengthen the community-based treatment of SAM.

Effect of fatty acid profiles in varying recipes of ready-to-use therapeutic foods on neurodevelopmental and clinical outcomes of children (6-59 months) with severe wasting: a systematic review.

CONTEXT: In 2020, 13.6 million children under 5 years suffered from severe acute malnutrition (SAM)/wasting. Standard ready-to-use therapeutic foods (RUTFs) improve polyunsaturated fatty acid (PUFA) status but contain suboptimal amounts of omega-3 (n-3) PUFAs with unbalanced n-6-to-n-3 PUFA ratios. OBJECTIVES: The aim was to compare the effects of RUTFs with different essential fatty acid contents on PUFA status, neurodevelopmental, and clinical outcomes (mortality, comorbidities, and recovery) of children with severe wasting. DATA SOURCES: Twelve databases, trial repositories, and article references with no publication limitations. DATA EXTRACTION: Ten studies from randomized, quasi, and cluster-randomized controlled trials providing RUTFs as home treatment to children 6-59 months with SAM/wasting were included. DATA ANALYSIS: Plasma phospholipid eicosapentaenoic acid content was higher in children receiving RUTF with altered essential fatty acid contents compared with standard RUTF (0.20 [0.15-0.25], P < 0.00001). Docosahexaenoic acid (DHA) status only improved in children receiving RUTF with added fish oil (0.33 [0.15-0.50], P = 0.0003). The Malawi Developmental Assessment tool (MDAT) global development and problem-solving assessment scores were higher in global assessment and gross motor domains in children receiving added fish oil compared with standard formulation (0.19 [0.0-0.38] and 0.29 [0.03-0.55], respectively). Children receiving high-oleic-acid RUTF (lowering the n-6:n-3 PUFA ratio of the RUTF) with or without fish oil had significantly higher scores in social domains compared with those receiving the standard formulation (0.16 [0.00-0.31] and 0.24 [0.09-0.40]). Significantly higher mortality risk was found in children receiving a standard formulation compared with RUTF with a lower n-6:n-3 PUFA ratio (0.79 [0.67-0.94], P = 0.008). CONCLUSION: Although lowering n-6:n-3 PUFA ratios did not increase plasma DHA, it improved specific neurodevelopmental scores and mortality due to lower linoleic acid (high-oleic-acid peanuts), higher alpha-linolenic acid (altered oil), or both. Additional preformed n-3 long-chain PUFAs (fish oil) with RUTF improved the children's DHA status, neurodevelopmental outcomes, and weight-for-height z score. More research is needed regarding cost, availability, stability, acceptability, and the appropriate amount of n-3 long-chain PUFAs required in RUTFs for the best clinical outcomes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42022303694.

Prevotella copri-related effects of a therapeutic food for malnutrition.

Preclinical and clinical studies are providing evidence that the healthy growth of infants and children reflects, in part, healthy development of their gut microbiomes1-5. This process of microbial community assembly and functional maturation is perturbed in children with acute malnutrition. Gnotobiotic animals, colonized with microbial communities from children with severe and moderate acute malnutrition, have been used to develop microbiome-directed complementary food (MDCF) formulations for repairing the microbiomes of these children during the weaning period5. Bangladeshi children with moderate acute malnutrition (MAM) participating in a previously reported 3-month-long randomized controlled clinical study of one such formulation, MDCF-2, exhibited significantly improved weight gain compared to a commonly used nutritional intervention despite the lower caloric density of the MDCF6. Characterizing the 'metagenome assembled genomes' (MAGs) of bacterial strains present in the microbiomes of study participants revealed a significant correlation between accelerated ponderal growth and the expression by two Prevotella copri MAGs of metabolic pathways involved in processing of MDCF-2 glycans1. To provide a direct test of these relationships, we have now performed 'reverse translation' experiments using a gnotobiotic mouse model of mother-to-offspring microbiome transmission. Mice were colonized with defined consortia of age- and ponderal growth-associated gut bacterial strains cultured from Bangladeshi infants/children in the study population, with or without P. copri isolates resembling the MAGs. By combining analyses of microbial community assembly, gene expression and processing of glycan constituents of MDCF-2 with single nucleus RNA-Seq and mass spectrometric analyses of the intestine, we establish a principal role for P. copri in mediating metabolism of MDCF-2 glycans, characterize its interactions with other consortium members including Bifidobacterium longum subsp. infantis, and demonstrate the effects of P. copri-containing consortia in mediating weight gain and modulating the activities of metabolic pathways involved in lipid, amino acid, carbohydrate plus other facets of energy metabolism within epithelial cells positioned at different locations in intestinal crypts and villi. Together, the results provide insights into structure/function relationships between MDCF-2 and members of the gut communities of malnourished children; they also have implications for developing future prebiotic, probiotic and/or synbiotic therapeutics for microbiome restoration in children with already manifest malnutrition, or who are at risk for this pervasive health challenge.

Vitamin B12 Status before and after Outpatient Treatment of Severe Acute Malnutrition in Children Aged 6-59 Months: A Sub-Study of a Randomized Controlled Trial in Burkina Faso.

Severe acute malnutrition (SAM) is treated with ready-to-use therapeutic foods (RUTF) containing a vitamin-mineral premix. Yet little is known about micronutrient status in children with SAM before and after treatment. We aimed to investigate vitamin B12 status in children with uncomplicated SAM, aged 6-59 months in Burkina Faso, before and after treatment with a standard or a reduced dose of RUTF. Blood samples were collected at admission and discharge. Serum B12 was determined with microbiological assay and serum methylmalonic acid (MMA) and total homocysteine (tHcy) were analyzed with gas chromatography-tandem mass spectrometry. B12 status was classified using the combined indicator (3cB12). Among 374 children, the median [interquartile range] age was 11.0 [7.7-16.9] months, and 85.8% were breastfed. Marked or severe B12 deficiency, as judged by 3cB12, decreased from 32% to 9% between admission and discharge (p < 0.05). No differences in B12 status following treatment with either standard (n = 194) or reduced (n = 180) doses of RUTF were observed. Breastfed children showed a lower B12 status (3cB12) than non-breastfed ones (-1.10 vs -0.18, p < 0.001 at admission; -0.44 vs 0.19; p < 0.001 at discharge). In conclusion, treatment of SAM with RUTF improved children's B12 status but did not fully correct B12 deficiency.

Effectiveness of Dietary Management for Moderate Wasting among Children > 6 Months of Age-A Systematic Review and Meta-Analysis Exploring Different Types, Quantities, and Durations.

Currently, no World Health Organization guidelines exist for the management of approximately 31.8 million moderately wasted children globally. The objective of this review was to synthesise evidence on the optimal type, quantity, and duration of dietary treatment for moderate wasting. Ten electronic databases were searched until the 23rd of August 2021. Experimental studies comparing interventions for the dietary management of moderate wasting were included. Meta-analyses were conducted and results were presented as risk ratios or mean differences with 95% confidence intervals. Seventeen studies comparing specially formulated foods were included involving 23,005 participants. Findings suggest little or no difference in recovery between Fortified Blended Foods (FBFs) with improved micronutrient and/or milk content (enhanced FBFs) and lipid-based nutrient supplements (LNS), whereas children treated with non-enhanced FBFs (locally produced FBFs or standard corn-soy blend) may have lower recovery rates than those treated with LNS. There was no difference in recovery when ready-to-use therapeutic and ready-to-use supplementary food were compared. Other outcomes mostly aligned with results for recovery. In conclusion, LNSs improve recovery compared to non-enhanced FBFs, but are comparable to enhanced FBFs. Programmatic choice of supplement should consider factors such as cost, cost-effectiveness, and acceptability. Further research is required to determine optimal dosing and duration of supplementation.

The effect of short-term preoperative nutritional intervention for cleft surgery eligibility.

BACKGROUND: Children with orofacial clefts are highly susceptible to malnutrition, with severe malnutrition restricting their eligibility to receive safe surgery. Ready-to-use therapeutic foods (RUTF) are an effective treatment for malnutrition; however, the effectiveness has not been demonstrated in this patient population prior to surgery. We studied the effectiveness of short-term RUTF use in transitioning children with malnutrition, who were initially ineligible for surgery, into surgical candidates. METHODS: A cohort of patients from Ghana, Honduras, Malawi, Madagascar, Nicaragua, and Venezuela enrolled in a nutrition program were followed by Operation Smile from June 2017 to January 2020. Age, weight, and length/height were tracked at each visit. Patients were included until they were sufficiently nourished (Z > = -1) with a secondary outcome of receiving surgery. The study was part of a collaborative program between Operation Smile (NGO), Birdsong Peanuts (peanut shellers and distributors), and MANA Nutrition (RUTF producer). RESULTS: A total of 556 patients were recruited between June 2017 and January 2020. At baseline 28.2% (n = 157) of patients were diagnosed with severe, 21.0% (n = 117) moderate, and 50.7% (n = 282) mild malnutrition. 324 (58.3%) presented for at least one return visit. Of those, 207 (63.7%) reached optimal nutrition status. By visit two, the mean z-score increased from -2.5 (moderate) to -1.7 (mild) (p < 0·001). The mean time to attain optimal nutrition was 6 weeks. There was a significant difference in the proportion of patients who improved by country(p < 0.001). CONCLUSION: Malnutrition prevents many children with orofacial clefts in low- and middle-income countries from receiving surgical care even when provided for free. This creates an even larger disparity in access to surgery. In an average of 6 weeks with an approximate cost of $25 USD per patient, RUTF transitioned over 60% of patients into nutritionally eligible surgical candidates, making it an effective, short-term preoperative nutritional intervention. Through unique partnerships, the expansion of cost-effective, large-scale nutrition programs can play a pivotal role in ensuring those at the highest risk of living with unrepaired orofacial clefts receive timely and safe surgical care.

Bioactive glycans in a microbiome-directed food for malnourished children.

Evidence is accumulating that perturbed postnatal development of the gut microbiome contributes to childhood malnutrition1-4. Designing effective microbiome-directed therapeutic foods to repair these perturbations requires knowledge about how food components interact with the microbiome to alter its expressed functions. Here we use biospecimens from a randomized, controlled trial of a microbiome-directed complementary food prototype (MDCF-2) that produced superior rates of weight gain compared to a conventional ready-to-use supplementary food (RUSF) in 12-18-month-old Bangladeshi children with moderate acute malnutrition (MAM)4. We reconstructed 1000 bacterial genomes (metagenome-assembled genomes, MAGs) present in their fecal microbiomes, identified 75 whose abundances were positively associated with weight gain (change in weight-for-length Z score, WLZ), characterized gene expression changes in these MAGs as a function of treatment type and WLZ response, and used mass spectrometry to quantify carbohydrate structures in MDCF-2 and feces. The results reveal treatment-induced changes in expression of carbohydrate metabolic pathways in WLZ-associated MAGs. Comparing participants consuming MDCF-2 versus RUSF, and MDCF-2-treated children in the upper versus lower quartiles of WLZ responses revealed that two Prevotella copri MAGs positively associated with WLZ were principal contributors to MDCF-2-induced expression of metabolic pathways involved in utilization of its component glycans. Moreover, the predicted specificities of carbohydrate active enzymes expressed by polysaccharide utilization loci (PULs) in these two MAGs correlate with the (i) in vitro growth of Bangladeshi P. copri strains, possessing differing degrees of PUL and overall genomic content similarity to these MAGs, cultured in defined medium containing different purified glycans representative of those in MDCF-2, and (ii) levels of carbohydrate structures identified in feces from clinical trial participants. In the accompanying paper5, we use a gnotobiotic mouse model colonized with age- and WLZ-associated bacterial taxa cultured from this study population, and fed diets resembling those consumed by study participants, to directly test the relationship between P. copri, MDCF-2 glycan metabolism, host ponderal growth responses, and intestinal gene expression and metabolism. The ability to identify bioactive glycan structures in MDCFs that are metabolized by growth-associated bacterial taxa will help guide recommendations about use of this MDCF for children with acute malnutrition representing different geographic locales and ages, as well as enable development of bioequivalent, or more efficacious, formulations composed of culturally acceptable and affordable ingredients.