Amino acid-enriched plant-based RUTF treatment was not inferior to peanut-milk RUTF treatment in restoring plasma amino acid levels among patients with oedematous or non-oedematous malnutrition.

Ready-to-use therapeutic food (RUTF) with adequate quality protein is used to treat children with oedematous and non-oedematous severe acute malnutrition (SAM). The plasma amino acid (AA) profile reflects the protein nutritional status; hence, its assessment during SAM treatment is useful in evaluating AA delivery from RUTFs. The objective was to evaluate the plasma AAs during the treatment of oedematous and non-oedematous SAM in community-based management of acute malnutrition (CMAM) using amino acid-enriched plant-based RUTFs with 10% milk (MSMS-RUTF) or without milk (FSMS-RUTF) compared to peanut milk RUTF (PM-RUTF). Plasma AA was measured in a non-blinded, 3-arm, parallel-group, simple randomized controlled trial conducted in Malawi. The RUTFs used for SAM were FSMS-RUTF, MSMS-RUTF or PM-RUTF. A non-inferiority hypothesis was tested to compare plasma AA levels from patients treated with FSMS-RUTF or MSMS-RUTF with those from patients treated with PM-RUTF at discharge. For both types of SAM, FSMS-RUTF and MSMS-RUTF treatments were non-inferior to the PM-RUTF treatment in restoration of the EAA and cystine except that for FSMS-RUTF, methionine and tryptophan partially satisfied the non-inferiority criteria in the oedematous group. Amino-acid-enriched milk-free plant-source-protein RUTF has the potential to restore all the EAA, but it is possible that enrichment with amino acids may require more methionine and tryptophan for oedematous children.

Soya, maize and sorghum ready-to-use therapeutic foods are more effective in correcting anaemia and iron deficiency than the standard ready-to-use therapeutic food: randomized controlled trial.

BACKGROUND: The prevalence of anaemia and iron deficiency (ID) among children with severe acute malnutrition (SAM) and their correction during nutritional rehabilitation are not well documented. This study assessed anaemia and ID prevalence and their predictors at start of SAM treatment, and the efficacy of their treatment and effect on gut health of two novel Ready-To-Use Therapeutic foods (RUTF) prepared from soybean, maize and sorghum (SMS) with (MSMS-RUTF) or without added milk (FSMS-RUTF) compared to those of the standard formulation prepared from peanut and milk (PM-RUTF). METHODS: This was a 3-arms parallel groups, simple randomised, controlled non-inferiority trial in 6-59 months old Central Malawian children with SAM. Anaemia was defined using altitude- and ethnicity-adjusted haemoglobin. Iron status was defined using soluble transferrin receptor (sTfR) and body iron stores (BIS). We used Pearson's chi-square test, t-test for paired or unpaired data, Kruskal-Wallis test for between-arm differences as appropriate and logistic regression to identify independent predictors of anaemia or iron deficiency anaemia (IDA). RESULTS: The sample size was 389. At admission, the prevalence [%(95%CI)] of anaemia was 48.9(41.4-56.5)% while that of ID and IDA were 55.7(48.6-62.5)% and 34.3(28.2-41.0)% when using sTfR criterion and 29.1(24.4-34.4)% and 28.9(23.7-34.9)% when using BIS criterion, respectively. At discharge, nutrition rehabilitation with SMS-RUTF was associated with the lowest prevalence of anaemia [12.0(6.9-20.3)% for FSMS-RUTF, 18.2(11.9-26.8)% for MSMS-RUTF and 24.5(15.8-35.9)% for PM-RUTF; p = 0.023] and IDA [7.9(3.4-17.3)% for FSMS-RUTF, 10.9(4.8-22.6)% for MSMS-RUTF and 20.5(10.7-35.5)% for PM-RUTF; p = 0.028]. SMS-RUTF was also associated with the highest increase in BIS [Change in BIS (95%CI)] among the iron deplete at admission [6.2 (3.7; 8.6), 3.2 (0.8; 5.6), 2.2 (0.2; 4.3) for the same study arms; Anova p = 0.045]. Compared to P-RUTF, FSMS-RUTF had the highest adjusted recovery rate [OR (95%CI = 0.3 (0.2-0.5) with p < 0.001 for FSMS-RUTF and 0.6 (0.3-1.0) with p = 0.068 for MSMS-RUTF]. No effect of iron content on risk of iron overload or gut inflammation was observed. CONCLUSIONS: Anaemia and ID are common among children with SAM. FSMS-RUTF is more efficacious in treating anaemia and correcting BIS among this group than PM-RUTF. TRIAL REGISTRATION: This study was registered on 15 April 2015 ( PACTR201505001101224 ).

Amino-acid-enriched cereals ready-to-use therapeutic foods (RUTF) are as effective as milk-based RUTF in recovering essential amino acid during the treatment of severe acute malnutrition in children: An individually randomized control trial in Malawi.

BACKGROUND: Ready-to-use therapeutic food (RUTF) is used to treat children suffering from severe acute malnutrition (SAM). Standard RUTF uses milk as the primary protein source, which makes the product expensive, and given the high worldwide SAM burden, having a less expensive effective alternative is a public health priority. OBJECTIVE: The objective of this study was to evaluate whether newly developed amino acid-enriched milk-free RUTF (FSMS-RUTF) or amino acid-enriched low-milk RUTF (MSMS-RUTF) treatment could replenish plasma amino acids to levels comparable to those following standard peanut-milk RUTF (PM-RUTF) treatment and to improve understanding of the effects of treatment on anthropometric measurements. A secondary analysis was performed to test the noninferiority hypothesis of plasma essential amino acid (EAA) levels. METHODS: Plasma EAA levels were measured in a nonblinded, 3-arm, parallel-group simple randomized controlled trial conducted in Malawi to examine the efficacy of FSMS-RUTF, MSMS-RUTF and PM-RUTF in the treatment of SAM in 2 groups of children aged 6-23 and 24-59 months (mo). Sample size calculations were performed based on the previous our study. A noninferiority margin was set at -25% of the PM-RUTF arm at discharge. RESULTS: The relative values of the differences (95% CI) in plasma EAA levels between PM-RUTF treatment and FSMS-RUTF and MSMS-RUTF treatments at discharge were -7.9% (-18.6, 2.8) and 9.8% (0.2, 19.5), respectively, in children aged 6-23 mo, while in those aged 24-59 mo, the difference values were 17.8% (1.6, 34.1) and 13.6% (-2.8, 29.9), respectively. CONCLUSION: At discharge, the plasma EAA concentrations in 6-59-mo-old SAM children treated with FSMS-RUTF and MSMS-RUTF were not less than those of children treated with PM-RUTF. These findings indicate that treatment with either of the 3 RUTFs was associated with adequate protein synthesis and that all the formulations provided sufficient functional metabolites of plasma amino acids to support nutritional recovery from SAM.

Soya, maize, and sorghum-based ready-to-use therapeutic food with amino acid is as efficacious as the standard milk and peanut paste-based formulation for the treatment of severe acute malnutrition in children: a noninferiority individually randomized controlled efficacy clinical trial in Malawi.

Background: Development of more cost-effective ready-to-use therapeutic food (RUTF) is a global public health priority. To date, previous lower-cost recipes have been less effective than the standard peanut and milk (PM)-based RUTF, particularly in children aged <24 mo.Objective: We aimed to compare the efficacy of the PM-RUTF to a milk-free soya, maize, and sorghum (FSMS)-RUTF enriched with crystalline amino acids without cow milk powder and a milk, soya, maize, and sorghum (MSMS)-RUTF containing 9.3% skim cow milk powder.Design: This nonblinded, 3-arm, parallel-group, simple randomized controlled trial enrolled Malawian children with severe acute malnutrition.Results: In intention-to-treat analyses, FSMS-RUTF showed noninferiority for recovery rates in children aged 24-59 mo (Δ: -1.9%; 95% CI: -9.5%, 5.6%) and 6-23 mo (Δ: -0.2%; 95% CI: -7.5%, 7.1%) compared with PM-RUTF. MSMS-RUTF also showed noninferiority for recovery rates in children aged 24-59 mo (Δ: 0.0%; 95% CI: -7.3%, 7.4%) and 6-23 mo (Δ: 0.6%; 95% CI: -4.3%, 5.5%). Noninferiority in recovery rates was also observed in per-protocol analyses. For length of stay in the program (time to cure), both FSMS-RUTF in children aged 24-59 mo (Δ: 2.8 d; 95% CI: -0.8, 6.5 d) and 6-23 mo (Δ: 3.4 d; 95% CI: -1.2, 8.0 d) and MSMS-RUTF in children aged 24-59 mo (Δ: 0.2 d; 95% CI: -3.1, 3.6 d) and 6-23 mo (Δ: 1.2 d; 95% CI: -3.4, 5.8 d) were not inferior to PM-RUTF. FSMS-RUTF was also significantly better than PM-RUTF at increasing hemoglobin and body iron stores in anemic children, with mean hemoglobin increases of 2.1 (95% CI: 1.6, 2.6) and 1.3 (95% CI: 0.9, 1.8) and mean body iron store increases of 2.0 (95% CI: 0.8, 3.3) and 0.1 (95% CI: -1.1, 1.3) for FSMS-RUTF and PM-RUTF, respectively.Conclusions: FSMS-RUTF without milk is efficacious in the treatment of severe acute malnutrition in children aged 6-23 and 24-59 mo. It is also better at correcting iron deficiency anemia than PM-RUTF. This trial was registered at www.pactr.org as PACTR201505001101224.

Safety and practicability of using mid-upper arm circumference as a discharge criterion in community based management of severe acute malnutrition in children aged 6 to 59 months programmes.

BACKGROUND: The use of proportional weight gain as a discharge criterion for MUAC admissions to programs treating severe acute malnutrition (SAM) is no longer recommended by WHO. The critical limitation with the proportional weight gain criterion was that children who are most severely malnourished tended to receive shorter treatment compared to less severely malnourished children. Studies have shown that using a discharge criterion of MUAC ≥ 125 mm eliminates this problem but concerns remain over the duration of treatment required to reach this criterion and whether this discharge criterion is safe. This study assessed the safety and practicability of using MUAC ≥ 125 mm as a discharge criterion for community based management of SAM in children aged 6 to 59 months. METHODS: A standards-based trial was undertaken in health facilities for the outpatient treatment of SAM in Lilongwe District, Malawi. 258 children aged 6 to 51 months were enrolled with uncomplicated SAM as defined by a MUAC equal or less than 115 mm without serious medical complications. Children were discharged from treatment as 'cured' when they achieved a MUAC of 125 mm or greater for two consecutive visits. After discharge, children were followed-up at home every two weeks for three months. RESULTS: This study confirms that a MUAC discharge criterion of 125 mm or greater is a safe discharge criterion and is associated with low levels of relapse to SAM (1.9 %) and mortality (1.3 %) with long durations of treatment seen only in the most severe SAM cases. The proportion of children experiencing a negative outcome was 3.2 % and significantly below the 10 % standard (p = 0.0013) established for the study. All children with negative outcomes had achieved weight-for-height z-score (WHZ) above -1 z-scores at discharge. Children admitted with lower MUAC had higher proportional weight gains (p < 0.001) and longer lengths of stay (p < 0.0001). MUAC at admission and attendance were both independently associated with cure (p < 0.0001). There was no association with negative outcomes at three months post discharge for children with heights at admission below 65 cm than for taller children (p = 0.5798). CONCLUSIONS: These results are consistent with MUAC ≥ 125 mm for two consecutive visits being a safe and practicable discharge criterion. Use of a MUAC threshold of 125 mm for discharge achieves reasonable lengths of stay and was also found to be appropriate for children aged six months or older who are less than 65 cm in height at admission. Early detection and recruitment of SAM cases using MUAC in the community and compliance with the CMAM treatment protocols should reduce lengths of stay and associated treatment costs.

Relationship between mid upper arm circumference and weight changes in children aged 6-59 months.

BACKGROUND: The objectives of this study were to (i) describe the relationship between weight changes and MUAC changes in children aged between 6 and 59 months during treatment for SAM in CMAM programmes in three country contexts (Malawi, Ethiopia and Bangladesh) admitted using MUAC and (ii) describe the sensitivity of both MUAC and weight to episodes of disease experienced during the SAM treatment episodes in CMAM programmes in three country contexts (Malawi, Ethiopia and Bangladesh) admitted using MUAC. METHODS: Data collected under research conditions in Malawi were analysed for the correlation between MUAC and weight changes using the Pearson product-moment correlation coefficient (Pearson's r). Further data from other CMAM programmes implemented under field conditions in Ethiopia and Bangladesh were similarly analysed. The association of growth failure following recent episodes of illness were assessed for MUAC and weight change using a two-by-two table, box-plots and Kruskal Wallis non-parametric rank sum test. RESULTS: MUAC and weight gain acheived over the entire treatment episode were strongly correlated in all three country contexts, Ethiopia (median Pearson's r = 0.816, 95 % CI = 0.782 - 0.845), Malawi (median Pearson's r = 0.843, 95 % CI = 0.802 - 0.876) and Bangladesh (median Pearson's r = 0.725, 95 % CI = 0.663 - 0.777). MUAC and weight changes at each outpatient visit were closely correlated (median Pearson's r = 0.954, 95 % CI = 0.602 - 0.997) under research conditions. The field data from Ethiopia and Bangladesh showed similar correlation (median Pearson's r = 0.945, 95 % CI = 0.685 - 0.998) and (median Pearson's r = 0.939, 95 % CI = 0.705 - 0.994) respectively. MUAC and weight appear to respond rapidly and similarly to episodes of illness reported during outpatient treatment for SAM for MUAC, diarrhoea RR = 1.88 (95 % CI = 1.64 - 2.15), vomiting RR = 1.89 (95 % CI = 1.58 - 2.26), fever RR = 1.57 (95 % CI = 1.36 - 1.82) and cough1.42 (95 % CI = 1.22 - 1.65). Similar relative risks are seen for weight; diarrhoea RR = 2.03 (95 % CI = 1.77 - 2.31), vomiting RR = 2.09 (95 % CI = 1.77 - 2.47), fever RR = 1.76 (95 % CI = 1.53 - 2.03) and cough RR = 1.25 (95 % CI = 1.06 - 1.48). CONCLUSIONS: This study demonstrates a close relationship between MUAC and weight change during recovery from SAM under both research and operational field conditions. Furthermore, changes in both MUAC and weight are observed to occur similarly and rapidly during episodes of illness occurring during treatment with no lag effect on the part of MUAC. This presents the possibility for children undergoing outpatient treatment for SAM to be monitored using MUAC as an alternative to weight. Further research would be required to develop a tool which can be deployed safely and enable MUAC to be used as the sole anthropometric measure for admission, monitoring of recovery and discharge. This development would potentially allow the further decentralisation of the treatment of SAM thus improving programme coverage and child survival.