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.

Nutritional treatment of children 6-59 months with severely low weight-for-age z-score: a study protocol for a 3-arm randomized controlled trial.

BACKGROUND: Admission criteria that treat children with low mid-upper-arm circumference (MUAC), and low weight-for-height z-score (WHZ) are not aligned with the evidence on which children are at risk of mortality. An analysis of community-based cohort data from Senegal found that a combination of weight-for-age (WAZ) and MUAC criteria identified all children at risk of near-term death associated with severe anthropometric deficits. This study will address whether children with WAZ <-3 but MUAC ≥125 mm benefit from therapeutic feeding with ready-to-use therapeutic foods (RUTF) and whether a simplified protocol is non-inferior to the weight-based standard protocol. METHODS: This is a prospective individually randomized controlled 3-arm trial conducted in the Nara health district in Mali. Children aged 6-59 months presenting with MUAC ≥125 mm and WAZ <-3 will be randomized to (1) control group receiving no treatment, (2) simplified treatment receiving 1 sachet of RUTF daily until WAZ ≥-3 for 2 visits, (3) standard treatment receiving RUTF according to WHZ category: (a) WHZ <-3 receive 200 kcal/kg/day until WHZ ≥-2 for 2 visits, (b) WHZ ≥-3 but <-2 receive 1 sachet daily until WHZ ≥-2 for 2 visits or (c) WHZ ≥-2 receive no treatment. All children will be followed up first fortnightly for 12 weeks and then monthly until 6 months post-enrolment. The primary endpoint will be measured at 2 months with the primary outcome being WAZ as a continuous measure. Other outcomes include other anthropometric measurements and a secondary endpoint will be observed at 6 months. A total of 1397 children will be recruited including 209 in the control and 594 in both the simplified and standard arms. The sample size should enable us to conclude on the superiority of the simplified treatment compared to no treatment and on the non-inferiority of the simplified treatment versus standard treatment with a margin of non-inferiority of 0.2 WAZ. DISCUSSION: This trial aims to generate new evidence on the benefit of treating children with WAZ <-3 but MUAC ≥125 mm in order to guide the choice of admission criteria to malnutrition treatment and build evidence on the most efficient treatment protocol. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov: NCT05248516 on February 21, 2022.

Effect of lipid-based nutrient supplements on micronutrient status and hemoglobin among children with stunting: secondary analysis of a randomized controlled trial in Uganda.

BACKGROUND: Micronutrient deficiencies and anemia are widespread among children with stunting. OBJECTIVES: We assessed the effects of lipid-based nutrient supplements (LNS) containing milk protein (MP) and/or whey permeate (WP) on micronutrient status and hemoglobin (Hb) among children with stunting. METHODS: This was a secondary analysis of a randomized controlled trial. Children aged 12-59 mo with stunting were randomly assigned to LNS (100 g/d) with milk or soy protein and WP or maltodextrin for 12 wk, or no supplement. Hb, serum ferritin (S-FE), serum soluble transferrin receptor (S-TfR), plasma cobalamin (P-Cob), plasma methylmalonic acid (P-MMA), plasma folate (P-Fol), and serum retinol-binding protein (S-RBP) were measured at inclusion and at 12 wk. Data were analyzed using linear and logistic mixed-effects models. RESULTS: Among 750 children, with mean age ± SD of 32 ± 11.7 mo, 45% (n = 338) were female and 98% (n = 736) completed follow-up. LNS, compared with no supplementation, resulted in 43% [95% confidence interval (CI): 28, 60] greater increase in S-FE corrected for inflammation (S-FEci), 2.4 (95% CI: 1.2, 3.5) mg/L greater decline in S-TfR, 138 (95% CI: 111, 164) pmol/L greater increase in P-Cob, 33% (95% CI: 27, 39) reduction in P-MMA, and 8.5 (95% CI: 6.6, 10.3) nmol/L greater increase in P-Fol. There was no effect of LNS on S-RBP. Lactation modified the effect of LNS on markers of cobalamin status, reflecting improved status among nonbreastfed and no effects among breastfed children. LNS increased Hb by 3.8 (95% CI: 1.7, 6.0) g/L and reduced the odds of anemia by 55% (odds ratio: 0.45, 95% CI: 0.29, 0.70). MP compared with soy protein increased S-FEci by 14% (95% CI: 3, 26). CONCLUSIONS: LNS supplementation increases Hb and improves iron, cobalamin, and folate status, but not vitamin A status among children with stunting. LNS should be considered for children with stunting. This trial was registered at ISRCTN as 13093195.

Effect of Milk Protein and Whey Permeate in Large-Quantity Lipid-Based Nutrient Supplement on Early Child Development among Children with Stunting: A Randomized 2 × 2 Factorial Trial in Uganda.

Stunting affects 22% children globally, putting them at risk of adverse outcomes including delayed development. We investigated the effect of milk protein (MP) vs. soy and whey permeate (WP) vs. maltodextrin in large-quantity, lipid-based nutrient supplement (LNS), and LNS itself vs. no supplementation, on child development and head circumference among stunted children aged 1-5 years. We conducted a randomized, double-blind, community-based 2 × 2 factorial trial in Uganda (ISRCTN1309319). We randomized 600 children to one of four LNS formulations (~535 kcal/d), with or without MP (n = 299 vs. n = 301) or WP (n = 301 vs. n = 299), for 12 weeks or to no supplementation (n = 150). Child development was assessed using the Malawi Development Assessment Tool. Data were analyzed using linear mixed-effects models. Children had a median [interquartile range] age of 30 [23; 41] months and mean ± standard deviation height-for-age z-score of -3.02 ± 0.74. There were no interactions between MP and WP for any of the outcomes. There was no effect of either MP or WP on any developmental domain. Although LNS itself had no impact on development, it resulted in 0.07 (95%CI: 0.004; 0.14) cm higher head circumference. Neither dairy in LNS, nor LNS in itself, had an effect on development among already stunted children.

Nutri-Score: Its Benefits and Limitations in Children's Feeding.

Reducing the burden of noncommunicable diseases (NCDs) is one of the top priorities of public health policies worldwide. One of the recognized means of achieving this objective is to improve the diet quality. The Nutri-Score (N-S) is a [five-color-A, B, C, D, E letters] front-of-pack labeling logo intended to help consumers quickly identify the healthier prepackaged foods within a food category. Available studies have shown that the N-S is an efficient tool to achieve this aim in terms of consumers' awareness, perception, understanding, and purchasing and that its use may help to reduce the prevalence of NCDs. The N-S is currently implemented on a voluntary basis in 7 European countries and a discussion is underway within the European Commission to achieve a harmonized mandatory label. However, no study on the putative impact of the N-S on children's dietary patterns and health is available. The N-S is not applicable to infants' and young children's formulas and to specific baby foods, the compositions of which are already laid down in European Union regulations. The N-S does not replace age-appropriate dietary guidelines. As children consume an increasing number of adult type and processed foods, the relevance of the N-S for children should be evaluated considering the children's high specific requirements, especially in younger children. This is especially necessary for fitting fat and iron requirements, whereas protein-rich foods should be better framed. Moreover, efforts should be made to inform on how to use the N-S and in education on healthy diets.

Serum cobalamin in children with moderate acute malnutrition in Burkina Faso: Secondary analysis of a randomized trial.

BACKGROUND: Among children with moderate acute malnutrition (MAM) the level of serum cobalamin (SC) and effect of food supplements are unknown. We aimed to assess prevalence and correlates of low SC in children with MAM, associations with hemoglobin and development, and effects of food supplements on SC. METHODS AND FINDINGS: A randomized 2 × 2 × 3 factorial trial was conducted in Burkina Faso. Children aged 6 to 23 months with MAM received 500 kcal/d as lipid-based nutrient supplement (LNS) or corn-soy blend (CSB), containing dehulled soy (DS) or soy isolate (SI) and 0%, 20%, or 50% of total protein from milk for 3 months. Randomization resulted in baseline equivalence between intervention groups. Data on hemoglobin and development were available at baseline. SC was available at baseline and after 3 and 6 months. SC was available from 1,192 (74.1%) of 1,609 children at baseline. The mean (±SD) age was 12.6 (±5.0) months, and 54% were females. Low mid-upper arm circumference (MUAC; <125 mm) was found in 80.4% (958) of the children and low weight-for-length z-score (WLZ; <-2) in 70.6% (841). Stunting was seen in 38.2% (456). Only 5.9% were not breastfed. Median (IQR) SC was 188 (137; 259) pmol/L. Two-thirds had SC ≤222 pmol/L, which was associated with lower hemoglobin. After age and sex adjustments, very low SC (<112 pmol/L) was associated with 0.21 (95% CI: 0.01; 0.41, p = 0.04) and 0.24 (95% CI: 0.06; 0.42, p = 0.01) z-score lower fine and gross motor development, respectively. SC data were available from 1,330 (85.9%) of 1,548 children followed up after 3 months and 398 (26.5%) of the 1,503 children after 6 months. Based on tobit regression, accounting for left censored data, and adjustments for correlates of missing data, the mean (95% CI) increments in SC from baseline to the 3- and 6-month follow-up were 72 (65; 79, p < 0.001) and 26 (16; 37, p < 0.001) pmol/L, respectively. The changes were similar among the 310 children with SC data at all 3 time points. Yet, the increase was 39 (20; 57, p < 0.001) pmol/L larger in children given LNS compared to CSB if based on SI (interaction, p < 0.001). No effect of milk was found. Four children died, and no child developed an allergic reaction to supplements. The main limitation of this study was that only SC was available as a marker of status and was missing from a quarter of the children. CONCLUSIONS: Low SC is prevalent among children with MAM and may contribute to impaired erythropoiesis and child development. The SC increase during supplementation was inadequate. The bioavailability and adequacy of cobalamin in food supplements should be reconsidered. TRIAL REGISTRATION: ISRCTN Registry ISRCTN42569496.

Children's Oxygen Administration Strategies And Nutrition Trial (COAST-Nutrition): a protocol for a phase II randomised controlled trial.

Background: To prevent poor long-term outcomes (deaths and readmissions) the integrated global action plan for pneumonia and diarrhoea recommends under the 'Treat' element of Protect, Prevent and Treat interventions the importance of continued feeding but gives no specific recommendations for nutritional support. Early nutritional support has been practiced in a wide variety of critically ill patients to provide vital cell substrates, antioxidants, vitamins, and minerals essential for normal cell function and decreasing hypermetabolism. We hypothesise that the excess post-discharge mortality associated with pneumonia may relate to the catabolic response and muscle wasting induced by severe infection and inadequacy of the diet to aid recovery. We suggest that providing additional energy-rich, protein, fat and micronutrient ready-to-use therapeutic feeds (RUTF) to help meet additional nutritional requirements may improve outcome. Methods: COAST-Nutrition is an open, multicentre, Phase II randomised controlled trial in children aged 6 months to 12 years hospitalised with suspected severe pneumonia (and hypoxaemia, SpO 2 <92%) to establish whether supplementary feeds with RUTF given in addition to usual diet for 56-days (experimental) improves outcomes at 90-days compared to usual diet alone (control). Primary endpoint is change in mid-upper arm circumference (MUAC) at 90 days and/or as a composite with 90-day mortality. Secondary outcomes include anthropometric status, mortality, readmission at days 28 and 180. The trial will be conducted in four sites in two countries (Uganda and Kenya) enrolling 840 children followed up to 180 days. Ancillary studies include cost-economic analysis, molecular characterisation of bacterial and viral pathogens, evaluation of putative biomarkers of pneumonia, assessment of muscle and fat mass and host genetic studies.   Discussion: This study is the first step in providing an option for nutritional support following severe pneumonia and will help in the design of a large Phase III trial. Registration: ISRCTN10829073 (6 th June 2018) PACTR202106635355751 (2 nd June 2021).

The Role of Milk Protein and Whey Permeate in Lipid-based Nutrient Supplements on the Growth and Development of Stunted Children in Uganda: A Randomized Trial Protocol (MAGNUS).

Stunting is associated with cognitive impairment and later chronic disease. Previous trials to prevent stunting have had little effect, and no trials seem to have provided larger amounts of energy and high-quality proteins to already stunted children. We aimed to assess the effects of milk protein (MP) and whey permeate (WP) in large-quantity lipid-based nutrient supplements (LNS-LQ), among stunted children, on linear growth and child development. This was a randomized, double-blind, 2-by-2 factorial trial. Stunted children aged 12-59 mo from eastern Uganda (n = 750) were randomly assigned to receive 100 g LNS-LQ with or without MP and WP (n = 4 × 150) or no supplement (n = 150) for 3 mo. The primary outcomes were change in knee-heel and total length. Secondary outcomes included child development, body composition, anthropometry, and hemoglobin. Micronutrient status, intestinal function, and microbiota were also assessed. Our findings will contribute to an understanding of the role of milk ingredients and LNS in linear catch-up growth. This trial was registered at www.isrctn.com as ISRCTN13093195.

Clinical Nutrition and Human Rights. An International Position Paper.

The International Working Group for Patients' Right to Nutritional Care presents its position paper regarding nutritional care as a human right intrinsically linked to the right to food and the right to health. All people should have access to food and evidence-based medical nutrition therapy including artificial nutrition and hydration. In this regard, the hospitalized malnourished ill should mandatorily have access to screening, diagnosis, nutritional assessment, with optimal and timely nutritional therapy in order to overcome malnutrition associated morbidity and mortality, while reducing the rates of disease-related malnutrition. This right does not imply there is an obligation to feed all patients at any stage of life and at any cost. On the contrary, this right implies, from an ethical point of view, that the best decision for the patient must be taken and this may include, under certain circumstances, the decision not to feed. Application of the human rights-based approach to the field of clinical nutrition will contribute to the construction of a moral, political, and legal focus to the concept of nutritional care. Moreover, it will be the cornerstone to the rationale of political and legal instruments in the field of clinical nutrition.

Clinical nutrition and human rights. An international position paper.

The International Working Group for Patients' Right to Nutritional Care presents its position paper regarding nutritional care as a human right intrinsically linked to the right to food and the right to health. All people should have access to food and evidence-based medical nutrition therapy including artificial nutrition and hydration. In this regard, the hospitalized malnourished ill should mandatorily have access to screening, diagnosis, nutritional assessment, with optimal and timely nutritional therapy in order to overcome malnutrition associated morbidity and mortality, while reducing the rates of disease-related malnutrition. This right does not imply there is an obligation to feed all patients at any stage of life and at any cost. On the contrary, this right implies, from an ethical point of view, that the best decision for the patient must be taken and this may include, under certain circumstances, the decision not to feed. Application of the human rights-based approach to the field of clinical nutrition will contribute to the construction of a moral, political and legal focus to the concept of nutritional care. Moreover, it will be the cornerstone to the rationale of political and legal instruments in the field of clinical nutrition.

Thymus size in children with moderate malnutrition: a cohort study from Burkina Faso.

BACKGROUND: Moderate acute malnutrition (MAM) affects millions of children, increasing their risk of dying from infections. Thymus atrophy may be a marker of malnutrition-associated immunodeficiency, but factors associated with thymus size in children with MAM are unknown, as is the effect of nutritional interventions on thymus size. METHODS: Thymus size was measured by ultrasound in 279 children in Burkina Faso with MAM, diagnosed by low mid-upper arm circumference (MUAC) and/or low weight-for-length z-score (WLZ), who received 12 weeks treatment with different food supplements as part of a randomized trial. Correlates of thymus size and of changes in thymus size after treatment, and after another 12 weeks of follow-up were identified. RESULTS: Thymus size correlated positively with age, anthropometry and blood haemoglobin, and was smaller in children with malaria. Children with malnutrition diagnosed using MUAC had a smaller thymus than children diagnosed based on WLZ. Thymus size increased during and after treatment, similarly across the different food supplement groups. CONCLUSIONS: In children with MAM, the thymus is smaller in children with anaemia or malaria, and grows with recovery. Assuming that thymus size reflects vulnerability, low MUAC seems to identify more vulnerable children than low WLZ in children with MAM. IMPACT: Thymus atrophy is known to be a marker of the immunodeficiency associated with malnutrition in children. In children with moderate malnutrition, we found the thymus to be smaller in children with anaemia or malaria. Assuming that thymus size reflects vulnerability, low MUAC seems to identify more vulnerable children than low weight for length. Thymus atrophy appears reversible with recovery from malnutrition, with similar growth seen in children randomized to treatment with different nutritional supplements.

Religious dietary rules and their potential nutritional and health consequences.

BACKGROUND: The vast majority of the world population declares affiliation to a religion, predominantly Christianity and Islam. Many religions have special dietary rules, which may be more or less strictly adhered to. METHODS: Religious food rules were collected from holy books and religious websites as well as their translation into dietary practices. The literature was searched for potential associations between these rules and potential nutritional consequences. RESULTS: Jewish, Islamic and Indian religions support prolonged breastfeeding. Religious avoidance of alcohol is probably beneficial to health. When strictly applied, a few rules may lead to nutritional inadequacies, mainly in populations living in unfavourable socio-economic or environmental conditions. In Jewish and Muslim observants, animal slaughtering procedures may increase the risk of iron deficiency. Jews may be at risk of excess sodium intake related to home-prepared foods. A vegan diet, as observed by some believers, often by drifting from original precepts, or by some Hindus or Buddhists, may result in vitamin B12, calcium, iron, zinc, selenium and n-3 fatty acids deficiencies. CONCLUSION: When implemented in accordance with the rules, most religious food precepts are not detrimental to health, as suggested by the fact that they have more or less been followed for millennia. Nevertheless, some practices may lead to nutritional inadequacies, such as iron, calcium, vitamin D and vitamin B12 deficiencies. Patients with low socio-economic status, children and women of childbearing age are of particular risk of such deficiencies. Being aware of them should help health professionals to take an individualized approach to decide whether to supplement or not.

Impact of food supplements on early child development in children with moderate acute malnutrition: A randomised 2 x 2 x 3 factorial trial in Burkina Faso.

BACKGROUND: Lipid-based nutrient supplements (LNS) and corn-soy blends (CSBs) with varying soy and milk content are used in treatment of moderate acute malnutrition (MAM). We assessed the impact of these supplements on child development. METHODS AND FINDINGS: We conducted a randomised 2 × 2 × 3 factorial trial to assess the effectiveness of 12 weeks' supplementation with LNS or CSB, with either soy isolate or dehulled soy, and either 0%, 20%, or 50% of protein from milk, on child development among 6-23-month-old children with MAM. Recruitment took place at 5 health centres in Province du Passoré, Burkina Faso between September 2013 and August 2014. The study was fully blinded with respect to soy quality and milk content, while study participants were not blinded with respect to matrix. This analysis presents secondary trial outcomes: Gross motor, fine motor, and language development were assessed using the Malawi Development Assessment Tool (MDAT). Of 1,609 children enrolled, 54.7% were girls, and median age was 11.3 months (interquartile range [IQR] 8.2-16.0). Twelve weeks follow-up was completed by 1,548 (96.2%), and 24 weeks follow-up was completed by 1,503 (93.4%); follow-up was similar between randomised groups. During the study, 4 children died, and 102 children developed severe acute malnutrition (SAM). There was no difference in adverse events between randomised groups. At 12 weeks, the mean MDAT z-scores in the whole cohort had increased by 0.33 (95% CI: 0.28, 0.37), p < 0.001 for gross motor; 0.26 (0.20, 0.31), p < 0.001 for fine motor; and 0.14 (0.09, 0.20), p < 0.001 for language development. Children had larger improvement in language z-scores if receiving supplements with milk (20%: 0.09 [-0.01, 0.19], p = 0.08 and 50%: 0.11 [0.01, 0.21], p = 0.02), although the difference only reached statistical significance for 50% milk. Post hoc analyses suggested that this effect was specific to boys (interaction p = 0.02). The fine motor z-scores were also improved in children receiving milk, but only when 20% milk was added to CSB (0.18 [0.03, 0.33], p = 0.02). Soy isolate over dehulled soy increased language z-scores by 0.07 (-0.01, 0.15), p = 0.10, although not statistically significant. Post hoc analyses suggested that LNS benefited gross motor development among boys more than did CSB (interaction p = 0.04). Differences between supplement groups did not persist at 24 weeks, but MDAT z-scores continued to increase post-supplementation. The lack of an unsupplemented control group limits us from determining the overall effects of nutritional supplementation for children with MAM. CONCLUSIONS: In this study, we found that child development improved during and after supplementation for treatment of MAM. Milk protein was beneficial for language and fine motor development, while suggested benefits related to soy quality and supplement matrix merit further investigation. Supplement-specific effects were not found post-intervention, but z-scores continued to improve, suggesting a sustained overall effect of supplementation. TRIAL REGISTRATION: ISRCTN42569496.

Association between admission criteria and body composition among young children with moderate acute malnutrition, a cross-sectional study from Burkina Faso.

Children with moderate acute malnutrition (MAM) are treated based on low weight-for-length z-score (WLZ), low mid-upper arm circumference (MUAC) or both. This study aimed to assess associations of admission criteria and body composition (BC), to improve treatment of MAM. We undertook a cross-sectional study among 6-23 months old Burkinabe children with MAM. Fat-free (FFM) and fat mass (FM) were determined by deuterium dilution and expressed as FFM (FFMI) and FM index (FMI). Of 1,489 children, 439 (29.5%) were recruited by low MUAC only (MUAC-O), 734 (49.3%) by low WLZ and low MUAC (WLZ-MUAC) and 316 (21.2%) by low WLZ only (WLZ-O). Thus, 1,173 (78.8%) were recruited by low MUAC, with or without low WLZ (ALL-MUAC). After adjustments, WLZ-O had 89 g (95% confidence interval (CI) 5; 172) lower FFM compared to MUAC-O. Similarly, WLZ-O had 0.89 kg/m2 (95% CI 0.77; 1.01) lower FFMI compared to MUAC-O, whereas there was no difference for FMI. However, boys included by WLZ-O compared to MUAC-O had 0.21 kg/m2 (95% CI 0.05; 0.38) higher FMI. In contrast, girls included by WLZ-O had 0.17 (95% CI 0.01; 0.33) kg/m2 lower FMI compared to MUAC-O (interaction, p = 0.002). We found that different criteria for admission into MAM treatment programmes select children with differences in BC, especially FFMI.Trial registration: ISRCTN42569496.

Acute malnutrition recovery energy requirements based on mid-upper arm circumference: Secondary analysis of feeding program data from 5 countries, Combined Protocol for Acute Malnutrition Study (ComPAS) Stage 1.

BACKGROUND: Severe and moderate acute malnutrition (SAM and MAM) are currently treated with different food products in separate treatment programs. The development of a unified and simplified treatment protocol using a single food product aims to increase treatment program efficiency and effectiveness. This study, the first stage of the ComPAS trial, sought to assess rate of growth and energy requirements among children recovering from acute malnutrition in order to design a simplified, MUAC-based dosage protocol. METHODS: We obtained secondary data from patient cards of children aged 6-59 months recovering from SAM in outpatient therapeutic feeding programs (TFPs) and from MAM in supplementary feeding programs (SFPs) in five countries in Africa and Asia. We used local polynomial smoothing to assess changes in MUAC and proportional weight gain between clinic visits and assessed their normalized differences for a non-zero linear trend. We estimated energy needs to meet or exceed the growth observed in 95% of visits. RESULTS: This analysis used data from 5518 patients representing 33942 visits. Growth trends in MUAC and proportional weight gain were not significantly different, each lower at higher MUAC values: MUAC growth averaged 2mm/week at lower MUACs (100 to <110mm) and 1mm/week at higher MUACs (120mm to <125mm); and proportional weight gain declined from 3.9g/kg/day to 2.4g/kg/day across the same MUAC values. In 95% of visits by children with a MUAC 100mm to <125mm who were successfully treated, energy needs could be met or exceeded with 1,000 kilocalories a day. CONCLUSION: Two 92g sachets of Ready-to-Use Therapeutic Food (RUTF) (1,000kcal total) is proposed to meet the estimated total energy requirements of children with a MUAC 100mm to <115mm, and one 92g sachet of RUTF (500kcal) is proposed to meet half the energy requirements of children with a MUAC of 115 to <125mm. A simplified, combined protocol may enable a more holistic continuum of care, potentially contributing to increased coverage for children suffering from acute malnutrition.

Vitamin A and iron status of children before and after treatment of uncomplicated severe acute malnutrition.

BACKGROUND & AIMS: Treatment of children with uncomplicated severe acute malnutrition (SAM) is based on ready-to-use therapeutic foods (RUTF) and aims for quick regain of lost body tissues while providing sufficient micronutrients to restore diminished body stores. Little evidence exists on the success of the treatment to establish normal micronutrient status. We aimed to assess the changes in vitamin A and iron status of children treated for SAM with RUTF, and explore the effect of a reduced RUTF dose. METHODS: We collected blood samples from children 6-59 months old with SAM included in a randomised trial at admission to and discharge from treatment and analysed haemoglobin (Hb) and serum concentrations of retinol binding protein (RBP), ferritin (SF), soluble transferrin receptor (sTfR), C-reactive protein (CRP) and α1-acid glycoprotein (AGP). SF, sTfR and RBP were adjusted for inflammation (CRP and AGP) prior to analysis using internal regression coefficients. Vitamin A deficiency (VAD) was defined as RBP < 0.7 µmol/l, anaemia as Hb < 110 g/l, storage iron deficiency (sID) as SF < 12 µg/l, tissue iron deficiency (tID) as sTfR > 8.3 mg/l and iron deficiency anaemia (IDA) as both anaemia and sID. Linear and logistic mixed models were fitted including research team and study site as random effects and adjusting for sex, age and outcome at admission. RESULTS: Children included in the study (n = 801) were on average 13 months of age at admission to treatment and the median treatment duration was 56 days [IQR: 35; 91] in both arms. Vitamin A and iron status markers did not differ between trial arms at admission or at discharge. Only Hb was 1.7 g/l lower (95% CI -0.3, 3.7; p = 0.088) in the reduced dose arm compared to the standard dose, at recovery. Mean concentrations of all biomarkers improved from admission to discharge: Hb increased by 12% or 11.6 g/l (95% CI 10.2, 13.0), RBP increased by 13% or 0.12 µmol/l (95% CI 0.09, 0.15), SF increased by 36% or 4.4 µg/l (95% CI 3.1, 5.7) and sTfR decreased by 16% or 1.5 mg/l (95% CI 1.0, 1.9). However, at discharge, micronutrient deficiencies were still common, as 9% had VAD, 55% had anaemia, 35% had sID, 41% had tID and 21% had IDA. CONCLUSION: Reduced dose of RUTF did not result in poorer vitamin A and iron status of children. Only haemoglobin seemed slightly lower at recovery among children treated with the reduced dose. While improvement was observed, the vitamin A and iron status remained sub-optimal among children treated successfully for SAM with RUTF. There is a need to reconsider RUTF fortification levels or test other potential strategies in order to fully restore the micronutrient status of children treated for SAM.

Short Malnourished Children and Fat Accumulation With Food Supplementation.

BACKGROUND: In moderate acute malnutrition programs, it is common practice to not measure mid-upper arm circumference (MUAC) of children whose length is <67 cm. This is based on expert opinion that supplementation of shorter children with low MUAC and weight-for-height z score ≥-2 may increase risk of excessive fat accumulation. Our aim was to assess if shorter children gain more fat than taller children when treated for moderate acute malnutrition diagnosed by low MUAC alone. METHODS: In this observational study, we included children aged 6 to 23 months with a MUAC between 115 and 125 mm and a weight-for-height z score ≥-2. On the basis of length at admission, children were categorized as short if <67 cm and long if ≥67 cm. Linear mixed-effects models were used to assess body composition on the basis of deuterium dilution and skinfold thickness. RESULTS: After 12 weeks of supplementation, there was no difference in change in fat mass index (-0.038 kg/m2, 95% confidence interval [CI]: -0.257 to 0.181, P = .74) or fat-free mass index (0.061 kg/m2, 95% CI: -0.150 to 0.271, P = .57) in short versus long. In absolute terms, the short children gained both less fat-free mass (-230 g, 95% CI: -355 to -106, P < .001) and fat mass (-97 g, 95% CI: -205 to 10, P = .076). There was no difference in changes in absolute subscapular and triceps skinfold thickness and z scores (P > .5). CONCLUSIONS: Short children with low MUAC do not gain excessive fat during supplementation. With these data, we support a recommendation for policy change to include all children ≥6 months with low MUAC in supplementary feeding programs, regardless of length. The use of length as a criterion for measuring MUAC to determine treatment eligibility should be discontinued in policy and practice.

Combined Protocol for Acute Malnutrition Study (ComPAS) in rural South Sudan and urban Kenya: study protocol for a randomized controlled trial.

BACKGROUND: Acute malnutrition is a continuum condition, but severe and moderate forms are treated separately, with different protocols and therapeutic products, managed by separate United Nations agencies. The Combined Protocol for Acute Malnutrition Study (ComPAS) aims to simplify and unify the treatment of uncomplicated severe and moderate acute malnutrition (SAM and MAM) for children 6-59 months into one protocol in order to improve the global coverage, quality, continuity of care and cost-effectiveness of acute malnutrition treatment in resource-constrained settings. METHODS/DESIGN: This study is a multi-site, cluster randomized non-inferiority trial with 12 clusters in Kenya and 12 clusters in South Sudan. Participants are 3600 children aged 6-59 months with uncomplicated acute malnutrition. This study will evaluate the impact of a simplified and combined protocol for the treatment of SAM and MAM compared to the standard protocol, which is the national treatment protocol in each country. We will assess recovery rate as a primary outcome and coverage, defaulting, death, length of stay, average weekly weight gain and average weekly mid-upper arm circumference (MUAC) gain as secondary outcomes. Recovery rate is defined across both treatment arms as MUAC ≥125 mm and no oedema for two consecutive visits. Per-protocol and intention-to-treat analyses will be conducted. DISCUSSION: If the combined protocol is shown to be non-inferior to the standard protocol, updating guidelines to use the combined protocol would eliminate the need for separate products, resources and procedures for MAM treatment. This would likely be more cost-effective, increase availability of services, enable earlier case finding and treatment before deterioration of MAM into SAM, promote better continuity of care and improve community perceptions of the programme. TRIAL REGISTRATION: ISRCTN, ISRCTN30393230 . Registered on 16 March 2017.

Impact of food supplements on hemoglobin, iron status, and inflammation in children with moderate acute malnutrition: a 2 × 2 × 3 factorial randomized trial in Burkina Faso.

Background: Children with moderate acute malnutrition (MAM) are treated with lipid-based nutrient supplements (LNSs) or corn-soy blends (CSBs) but little is known about the impact of these supplements on hemoglobin, iron status, and inflammation. Objective: The objective of this study was to investigate the impact of supplementary foods for treatment of MAM on hemoglobin, iron status, inflammation, and malaria. Design: A randomized 2 × 2 × 3 factorial trial was conducted in Burkina Faso. Children aged 6-23 mo with MAM received 500 kcal/d as LNS or CSB, containing either dehulled soy (DS) or soy isolate (SI) and different quantities of dry skimmed milk (0%, 20% or 50% of total protein) for 12 wk. The trial was double-blind with regard to quality of soy and quantity of milk, but not matrix (CSB compared to LNS). Hemoglobin, serum ferritin (SF), serum soluble transferrin receptor (sTfR), serum C-reactive protein (CRP), serum α1-acid glycoprotein (AGP), and malaria antigens were measured at inclusion and after supplementation. Results: Between September 2013 and August 2014, 1609 children were enrolled. Among these, 61 (3.8%) were lost to follow-up. During the 12-wk supplementation period, prevalence of anemia, low SF adjusted for inflammation (SFAI), elevated sTfR, and iron-deficiency anemia decreased by 16.9, 8.7, 12.6 and 10.5 percentage points. Children who received LNS compared to CSB had higher hemoglobin (2 g/L; 95% CI: 1, 4 g/L), SFAI (4.2 µg/L; 95% CI: 2.9, 5.5 µg/L), and CRP (0.8 mg/L; 95% CI: 0.4, 1.2 mg/L) and lower sTfR (-0.9 mg/L, 95% CI: -1.3, -0.6 mg/L) after the intervention. Replacing DS with SI or increasing milk content did not affect hemoglobin, SFAI, sTfR, or CRP. Conclusion: Supplementation with LNS compared to CSB led to better hemoglobin and iron status, but overall prevalence of anemia remained high. The higher concentrations of acute-phase proteins in children who received LNSs requires further investigation. This trial was registered at www.controlled-trials.com as ISRCTN42569496.

Effectiveness of food supplements in increasing fat-free tissue accretion in children with moderate acute malnutrition: A randomised 2 × 2 × 3 factorial trial in Burkina Faso.

BACKGROUND: Children with moderate acute malnutrition (MAM) are treated with lipid-based nutrient supplement (LNS) or corn-soy blend (CSB). We assessed the effectiveness of (a) matrix, i.e., LNS or CSB, (b) soy quality, i.e., soy isolate (SI) or dehulled soy (DS), and (c) percentage of total protein from dry skimmed milk, i.e., 0%, 20%, or 50%, in increasing fat-free tissue accretion. METHODS AND FINDINGS: Between September 9, 2013, and August 29, 2014, a randomised 2 × 2 × 3 factorial trial recruited 6- to 23-month-old children with MAM in Burkina Faso. The intervention comprised 12 weeks of food supplementation providing 500 kcal/day as LNS or CSB, each containing SI or DS, and 0%, 20%, or 50% of protein from milk. Fat-free mass (FFM) was assessed by deuterium dilution technique. By dividing FFM by length squared, the primary outcome was expressed independent of length as FFM index (FFMI) accretion over 12 weeks. Other outcomes comprised recovery rate and additional anthropometric measures. Of 1,609 children, 4 died, 61 were lost to follow-up, and 119 were transferred out due to supplementation being switched to non-experimental products. No children developed allergic reaction. At inclusion, 95% were breastfed, mean (SD) weight was 6.91 kg (0.93), with 83.5% (5.5) FFM. In the whole cohort, weight increased 0.90 kg (95% CI 0.88, 0.93; p < 0.01) comprising 93.5% (95% CI 89.5, 97.3) FFM. As compared to children who received CSB, FFMI accretion was increased by 0.083 kg/m2 (95% CI 0.003, 0.163; p = 0.042) in those who received LNS. In contrast, SI did not increase FFMI compared to DS (mean difference 0.038 kg/m2; 95% CI -0.041, 0.118; p = 0.35), irrespective of matrix. Having 20% milk protein was associated with 0.097 kg/m2 (95% CI -0.002, 0.196) greater FFMI accretion than having 0% milk protein, although this difference was not significant (p = 0.055), and there was no effect of 50% milk protein (0.049 kg/m2; 95% CI -0.047, 0.146; p = 0.32). There was no effect modification by season, admission criteria, or baseline FFMI, stunting, inflammation, or breastfeeding (p > 0.05). LNS compared to CSB resulted in 128 g (95% CI 67, 190; p < 0.01) greater weight gain if both contained SI, but there was no difference between LNS and CSB if both contained DS (mean difference 22 g; 95% CI -40, 84; p = 0.49) (interaction p = 0.017). Accordingly, SI compared to DS increased weight by 89 g (95% CI 27, 150; p = 0.005) when combined with LNS, but not when combined with CSB. A limitation of this and other food supplementation trials is that it is not possible to collect reliable data on individual adherence. CONCLUSIONS: Based on this study, children with MAM mainly gain fat-free tissue when rehabilitated. Nevertheless, LNS yields more fat-free tissue and higher recovery rates than CSB. Moreover, current LNSs with DS may be improved by shifting to SI. The role of milk relative to soy merits further research. TRIAL REGISTRATION: ISRCTN registry ISRCTN42569496.