Standard RUTF vs. locally-made RUSF for acutely malnourished children: A quasi-experimental comparison of the impact on growth and compliance in a rural community of Pakistan.

BACKGROUND: The reduction in severe and moderate acute malnutrition (SAM and MAM) rates in Pakistan has been sub-optimal compared to other low-and middle-income countries (LMICs). Specially-formulated products have been designed globally to manage SAM and MAM, such as ready-to-use therapeutic food (RUTF) and ready-to-use supplementary food (RUSF), with variable efficacies. RUTF is primarily produced and patented in industrialized countries, raising supply challenges in resource-constrained regions with a high burden of acute malnutrition. RUSF minimizes costs by using locally-available ingredients while providing similar nutritional value. In this study, we compared the efficacy, side effects, and compliance of two months of supplementation with either RUTF or RUSF. METHODS: Children aged nine months in the rural district of Matiari, Pakistan, with a weight-for-height z-score (WHZ) <-2 received either RUTF (500 kcal sachet) for two months in 2015 or RUSF (520 kcal sachet) for two months in 2018. RESULTS: The RUSF group had a higher height gain and mid-upper arm circumferences (MUAC) score. Higher compliance was noted with lower side effects in the RUSF group. A higher compliance rate did correlate with the growth parameters in respective groups. CONCLUSION: Our study found that both RUTF and RUSF partially improve the anthropometric status of acutely malnourished children, with neither being superior to the other.

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.

Response to Malnutrition Treatment in Low Weight-for-Age Children: Secondary Analyses of Children 6-59 Months in the ComPAS Cluster Randomized Controlled Trial.

Weight-for-age z-score (WAZ) is not currently an admission criterion to therapeutic feeding programs, and children with low WAZ at high risk of mortality may not be admitted. We conducted a secondary analysis of RCT data to assess response to treatment according to WAZ and mid-upper arm circumference (MUAC) and type of feeding protocol given: a simplified, combined protocol for severe and moderate acute malnutrition (SAM and MAM) vs. standard care that treats SAM and MAM, separately. Children with a moderately low MUAC (11.5-12.5 cm) and a severely low WAZ (<-3) respond similarly to treatment in terms of both weight and MUAC gain on either 2092 kJ (500 kcal)/day of therapeutic or supplementary food. Children with a severely low MUAC (<11.5 cm), with/without a severely low WAZ (<-3), have similar recovery with the combined protocol or standard treatment, though WAZ gain may be slower in the combined protocol. A limitation is this analysis was not powered for these sub-groups specifically. Adding WAZ < -3 as an admission criterion for therapeutic feeding programs admitting children with MUAC and/or oedema may help programs target high-risk children who can benefit from treatment. Future work should evaluate the optimal treatment protocol for children with a MUAC < 11.5 and/or WAZ < -3.0.

Adequacy of Nutrient Intakes of Severely and Acutely Malnourished Children Treated with Different Doses of Ready-To-Use Therapeutic Food in Burkina Faso.

BACKGROUND: Ready-to-use therapeutic foods (RUTF) are designed to cover the daily nutrient requirements of children with severe acute malnutrition (SAM). However, with the transfer of uncomplicated SAM care from the hospital environment to the community level, children will be able to consume complementary and family foods (CFF) in addition to RUTF, and this might decrease the quantity of RUTF needed for recovery. OBJECTIVES: Using an individually randomized clinical trial, we investigated the effects of a reduced RUTF dose on the daily energy and macronutrient intakes, the proportion of energy coming from CFF, and the mean probability of adequacy (MPA) of intake in 11 micronutrients of 516 children aged 6-59 mo who were treated for SAM in Burkina Faso. METHODS: The data were collected using a single 24-h multipass dietary recall, 1 mo after starting treatment, from December 2016 to August 2018, repeated on a subsample of 66 children. Differences between children receiving the reduced RUTF (intervention arm) and those receiving standard RUTF (control arm) were assessed by linear mixed models. RESULTS: Daily energy intake was lower (P < 0.01) in the intervention arm (mean ± SD 1321 ± 339 kcal) than in the control arm (1467 ± 319 kcal). CFF contributed to 40% of the daily energy intake in the intervention and 35% in the control arm. The MPA for 11 micronutrients was 0.89 ± 0.1 in the intervention arm and 0.95 ± 0.07 in the control arm (P = 0.06). CONCLUSIONS: Reducing the dose of RUTF during SAM treatment had a negative impact on daily energy intake of the children. Despite this, children covered their recommended energy intake. The energy intake coming from CFF was similar between arms, suggesting that children's feeding practices did not change due to the reduction in RUTF in this context. This trial was registered at the IRSCTN registry as ISRCTN50039021.

Length of stay to recover from severe acute malnutrition and associated factors among under-five years children admitted to public hospitals in Aksum, Ethiopia.

BACKGROUND: Severe acute malnutrition is defined by <70% weight for length/height, by visible severe wasting, by the presence of pitting edema, and in children 6 to 59 months of age, mid upper arm circumference <110 mm. Severe acute malnutrition remains to be a worldwide problem, claiming lives of millions of children, especially in sub-Saharan Africa and south Asia. Though the Ethiopian national guideline states the total length of stay in therapeutic feeding units should not be more than four weeks, there is huge difference, varying from 8 to 47 days of stay. Therefore, the objective of this study was to assess length of stay to recover from severe acute malnutrition and associated factors among under five children hospitalized to the public hospitals in Aksum Town. METHODS: Sample size was calculated using STATA version 12.0. A retrospective cohort study was conducted using pretested questionnaire in the public hospitals in Aksum on children aged 0-59 months. Cleaned data was entered to Epi info version 7.1.4 and then exported into SPSS version 21 for analysis. Bivariable and multivariable analyses were performed using Kaplan Meier and Cox regression models. During bivariable analysis, variables with p-value < 0.05 were selected for multivariable analysis to identify independent factors associated with length of stay. RESULTS: A total of 564 participants enrolled to the study. The rate of recovery was 56% with median length of stay of 15 days (95% CI: 14.1, 15.9). The independent predictors of length of stay to recovery were presence of diarrhea at admission (AHR = 0.573, 95% CI: 0.415-0.793), being HIV positive (AHR = 0.391, 95% CI: 0.194-0.788), palmar pallor (AHR = 0.575, 95% CI: 0.416-0.794), presence of other co-morbidities at admission (AHR = 0.415, 95% CI: 0.302-0.570) and not being treated with plumpy nut (AHR = 0.368, 95% CI: 0.262-0.518). CONCLUSIONS: Length of stay is in the acceptable range of the international and national set of standards. Nevertheless, the recovery rate was lower compared to the Sphere standard. Presence of diarrhea, palmar pallor, HIV other co-morbidities and not treated with plumpy nut were found independent protective factors for recovery from sever acute malnutrition.

A simplified, combined protocol versus standard treatment for acute malnutrition in children 6-59 months (ComPAS trial): A cluster-randomized controlled non-inferiority trial in Kenya and South Sudan.

BACKGROUND: Malnutrition underlies 3 million child deaths worldwide. Current treatments differentiate severe acute malnutrition (SAM) from moderate acute malnutrition (MAM) with different products and programs. This differentiation is complex and costly. The Combined Protocol for Acute Malnutrition Study (ComPAS) assessed the effectiveness of a simplified, unified SAM/MAM protocol for children aged 6-59 months. Eliminating the need for separate products and protocols could improve the impact of programs by treating children more easily and cost-effectively, reaching more children globally. METHODS AND FINDINGS: A cluster-randomized non-inferiority trial compared a combined protocol against standard care in Kenya and South Sudan. Randomization was stratified by country. Combined protocol clinics treated children using 2 sachets of ready-to-use therapeutic food (RUTF) per day for those with mid-upper arm circumference (MUAC) < 11.5 cm and/or edema, and 1 sachet of RUTF per day for those with MUAC 11.5 to <12.5 cm. Standard care clinics treated SAM with weight-based RUTF rations, and MAM with ready-to-use supplementary food (RUSF). The primary outcome was nutritional recovery. Secondary outcomes included cost-effectiveness, coverage, defaulting, death, length of stay, and average daily weight and MUAC gains. Main analyses were per-protocol, with intention-to-treat analyses also conducted. The non-inferiority margin was 10%. From 8 May 2017 to 31 March 2018, 2,071 children were enrolled in 12 combined protocol clinics (mean age 17.4 months, 41% male), and 2,039 in 12 standard care clinics (mean age 16.7 months, 41% male). In total, 1,286 (62.1%) and 1,202 (59.0%), respectively, completed treatment; 981 (76.3%) on the combined protocol and 884 (73.5%) on the standard protocol recovered, yielding a risk difference of 0.03 (95% CI -0.05 to 0.10, p = 0.52; per-protocol analysis, adjusted for country, age, and sex). The amount of ready-to-use food (RUTF or RUSF) required for a child with SAM to reach full recovery was less in the combined protocol (122 versus 193 sachets), and the combined protocol cost US$123 less per child recovered (US$918 versus US$1,041). There were 23 (1.8%) deaths in the combined protocol arm and 21 (1.8%) deaths in the standard protocol arm (adjusted risk difference 95% CI -0.01 to 0.01, p = 0.87). There was no evidence of a difference between the protocols for any of the other secondary outcomes. Study limitations included contextual factors leading to defaulting, a combined multi-country power estimate, and operational constraints. CONCLUSIONS: Combined treatment for SAM and MAM is non-inferior to standard care. Further research should focus on operational implications, cost-effectiveness, and context (Asia versus Africa; emergency versus food-secure settings). This trial is complete and registered at ISRCTN (ISRCTN30393230). TRIAL REGISTRATION: The trial is registered at ISRCTN, trial number ISRCTN30393230.

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.

Body composition during outpatient treatment of severe acute malnutrition: Results from a randomised trial testing different doses of ready-to-use therapeutic foods.

BACKGROUND & AIMS: Treatment of children with uncomplicated severe acute malnutrition (SAM) is based on ready-to-use therapeutic foods (RUTF) prescribed based on body weight and administered at home. Treatment performance is typically monitored through weight gain. We previously reported that a reduced dose of RUTF resulted in weight gain velocity similar to standard dose. Here we investigate the change in body composition of children treated for SAM and compare it to community controls, and describe the effect of a reduced RUTF dose on body composition at recovery. METHODS: Body composition was measured via bio-electrical impedance analysis at admission and recovery among a sub-group of children with SAM participating in a clinical trial and receiving a reduced or a standard dose of RUTF. Non-malnourished children were measured to represent community controls. Linear mixed regression models were fitted. RESULTS: We obtained body composition data from 452 children at admission, 259 at recovery and 97 community controls. During SAM treatment the average weight increased by 1.20 kg of which 0.55 kg (45%) was fat-free mass (FFM) and 0.67 kg (55%) was fat mass (FM). At recovery, children treated for SAM had 1.27 kg lower weight, 0.38 kg lower FFM, and 0.90 kg lower FM compared to community controls. However, their fat-free mass index (FFMI) was not different from community controls (Δ0.2 kg/m2; 95% CI -0.1, 0.4). No differences were observed in FFM, FM or fat mass index (FMI) between the study arms at recovery. However, FFMI was 0.35 kg/m2 higher at recovery with the reduced compared to standard dose (p = 0.007) due to slightly lower height (Δ0.22 cm; p = 0.25) and higher FFM (Δ0.11 kg; p = 0.078) in the reduced dose group. CONCLUSIONS: Almost half of the weight gain during SAM treatment was FFM. Compared to community controls, children recovered from SAM had a lower FM while their height-adjusted FFM was similar. There was no evidence of a differential effect of a reduced RUTF dose on the tissue accretion of treated children when compared to standard treatment.

The recovery rate from severe acute malnutrition among under-five years of children remains low in sub-Saharan Africa. A systematic review and meta-analysis of observational studies.

BACKGROUND: Globally, Severe Acute Malnutrition (SAM) has been reduced by only 11% over the past 20 years and continues to be a significant cause of morbidity and mortality. So far, in Sub-Saharan Africa, several primary studies have been conducted on recovery rate and determinants of recovery from SAM in under-five children. However, comprehensive reviews that would have a shred of strong evidence for designing interventions are lacking. So, this review and meta-analysis was conducted to bridge this gap. METHODS: A systematic review of observational studies published in the years between 1/1/2000 to 12/31/2018 was conducted following the Meta-analysis of Observational Studies in Epidemiology (MOOSE) statement. Two reviewers have been searched and extracted data from CINAHL (EBSCO), MEDLINE (via Ovid), Emcare, PubMed databases, and Google scholar. Articles' quality was assessed using the Newcastle-Ottawa Scale by two independent reviewers, and only studies with fair to good quality were included in the final analysis. The review presented the pooled recovery rate from SAM and an odds ratio of risk factors affecting recovery rate after checking for heterogeneity and publication bias. The review has been registered in PROSPERO with protocol number CRD42019122085. RESULT: Children with SAM from 54 primary studies (n = 140,148) were included. A pooled rate of recovery was 71.2% (95% CI: 68.5-73.8; I2 = 98.9%). Children who received routine medication (Pooled Odds ratio (POR):1.85;95% CI: 1.49-2.29; I2 = 0.0%), older age (POR: 1.99;95% CI: 1.29-3.08; I2 = 80.6%), and absence of co-morbidity (POR:3.2;95% CI: 2.15-4.76; I2 = 78.7%) had better odds of recovery. This systematic review and meta-analysis suggestes HIV infected children had lower recovery rate from SAM (POR; 0.19; 95% CI: 0.09-0.39; I2 = 42.9%) compared to those non-infected. CONCLUSION: The meta-analysis deciphers that the pooled recovery rate was below the SPHERE standard, and further works would be needed to improve the recovery rate. So, factors that were identified might help to revise the plan set by the countries, and further research might be required to explore health fascilities fidelity to the WHO SAM management protocol.

Treatment of severe acute malnutrition with oat or standard ready-to-use therapeutic food: a triple-blind, randomised controlled clinical trial.

OBJECTIVE: We hypothesised that an alternative RUTF (ready-to-use therapeutic food) made with oats (oat-RUTF) would be non-inferior to standard RUTF (s-RUTF). DESIGN: This was a randomised, triple-blind, controlled, clinical non-inferiority trial comparing oat-RUTF to s-RUTF in rural Sierra Leone. Children aged 6-59 months with severe acute malnutrition (SAM) were randomised to oat-RUTF or s-RUTF. s-RUTF was composed of milk powder, sugar, peanut paste and vegetable oil, with a hydrogenated vegetable oil additive. Oat-RUTF contained oats and no hydrogenated vegetable oil additives. The primary outcome was graduation, an increase in anthropometric measurements such that the child was not acutely malnourished. Secondary outcomes were rates of growth, time to graduation and presence of adverse events. Intention to treat analyses was used. RESULTS: Of the 1406 children were enrolled, graduation was attained in 404/721 (56%) children receiving oat-RUTF and 311/685 (45%) receiving s-RUTF (difference 10.6%, 95% CI 5.4% to 15.8%). Death, hospitalisation or remaining with SAM was seen in 87/721 (12%) receiving oat-RUTF and in 125/685 (18%) receiving s-RUTF (difference 6.2%, 95% CI 2.3 to 10.0, p=0.001). Time to graduation was less for children receiving oat RUTF; 3.9±1.8 versus 4.5±1.8 visits, respectively (p<0.001). Rates of weight in the oat-RUTF group were greater than in the s-RUTF group; 3.4±2.7 versus 2.5±2.3 g/kg/d, p<0.001. CONCLUSION: Oat-RUTF is superior to s-RUTF in the treatment of SAM in Sierra Leone. We speculate that might be because of beneficial bioactive components or the absence of hydrogenated vegetable oil in oat-RUTF. TRIAL REGISTRATION NUMBER: NCT03407326.

Acceptability and efficacy of ready-to-use therapeutic food using soy protein isolate in under-5 children suffering from severe acute malnutrition in Bangladesh: a double-blind randomized non-inferiority trial.

BACKGROUND AND OBJECTIVE: Globally, around 20 million children suffer from severe acute malnutrition (SAM). Identifying a more economical treatment for those affected has the potential to make treatment more available and improve prognosis for recovery and future health. DESIGN/METHODS: The double-blind randomized study compared taste acceptability (measured by the eagerness to eat) and efficacy of soy-based RUTF (S-RUTF) with milk-based RUTF (M-RUTF) in 6- to 59-month-old children suffering from SAM (WHZ < -3) at icddr,b, in Bangladesh. These SAM children were enrolled in the study after completion of their stabilization phase of treatment. Tolerance of test-RUTF was also tested during the efficacy trial. RESULTS: The cross-over taste acceptability study, conducted in 36 children, revealed similar results between products and an absence of side effects. The efficacy trial enrolled 260 children (130, each group) with similar baseline characteristics, including mean ± SD age 15.0 ± 8.0 months, WHZ - 3.41 ± 0.40 and mid-upper arm circumference (MUAC) 11.1 ± 0.7 cm. The features at the end of study by RUTF group were (in S-RUTF vs. M-RUTF, respectively): total days from enrollment: 44 ± 34 versus 39 ± 30; weight gain (kg): 0.698 ± 0.438 versus 0.741 ± 0.381 and rate of weight gain (g/kg/d): 3.9 ± 3.2 versus 5.2 ± 4.6; MUAC gain (cm): 0.9 ± 0.7 versus 0.9 ± 0.6; and improvement of WHZ: 1.12 ± 0.82 versus 1.22 ± 0.68 (all data were man ± SD and none were significantly different between the groups). At enrollment and the end of intervention, the body composition [total body water (TBW): 70.3 ± 3.2 vs. 69.9 ± 3.5%, and fat: 11.0 ± 4.0 vs.11.5 ± 4.3% at baseline; and TBW: 65.5 ± 4.1 vs. 65.9 ± 4.6%; and fat: 16.8 ± 5.2 vs. 16.2 ± 5.8% in S-RUTF and M-RUTF group, respectively] was found similar. Moreover, the increment of total TBW, FM, and FFM was also observed similar between the groups. CONCLUSIONS: This is the first randomized trial comparing S-RUTF using soy protein isolate with milk-based RUTF including comparison of body composition. S-RUTF was found equally acceptable as of milk-based RUTF without any adverse event. Children receiving S-RUTF showed similar pattern of changes in anthropometric indices, and body composition as of milk-based RUTF. Greater number of SAM children can be managed in the community with comparatively low-cost soy-based RUTF. TRIAL REGISTRATION: NCT01634009.

Combined protocol for severe and moderate acute malnutrition in emergencies: Stakeholders perspectives in four countries.

Each year, acute malnutrition affects an estimated 52 million children under 5 years of age. Current global treatment protocols divide treatment of severe acute malnutrition (SAM) and moderate acute malnutrition (MAM) despite malnutrition being a spectrum disease. A proposed Combined Protocol provides for (a) treatment of MAM and SAM at the same location; (b) diagnosis using middle-upper-arm circumference (MUAC) and oedema only; (c) treatment using a single product, ready-to-use-therapeutic food (RUTF), and (d) a simplified dosage schedule for RUTF. This study examines stakeholders' knowledge of and opinions on the Combined Protocol in Niger, Nigeria, Somalia, and South Sudan. Data collection included a document review followed by in-depth interviews with 50 respondents from government, implementing partners, and multilateral agencies, plus 11 global and regional stakeholders. Data were analysed iteratively using thematic content analysis. We find that acute malnutrition protocols in these countries have not been substantially modified to include components of the Combined Protocol, although aspects were accepted for use in emergencies. Respondents generally agreed that MAM and SAM treatment should be provided in the same location, however they said MUAC and oedema-only diagnosis, although more field-ready than other diagnostic measures, did not necessarily catch all malnourished children and may not be appropriate for "tall and slim" morphologies. Similarly, using only RUTF presented inherent logistical advantages, but respondents worried about pipeline issues. Respondents did not express strong opinions about simplified dosage schedules. Stakeholders interviewed indicated more evidence is needed on the operational implications and effectiveness of the Combined Protocol in different contexts.

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 ).

Time of recovery and associated factors of children with severe acute malnutrition treated at outpatient therapeutic feeding program in Dire Dawa, Eastern Ethiopia.

BACKGROUND: The outpatient therapeutic feeding program is one dimension of the Community Based Management of Acute Malnutrition (CMAM) that provides screening, diagnostic and treatment services for children with Severe Acute Malnutrition (SAM). However, little is known about the program outcomes and factors affecting time to recovery. OBJECTIVES: To determine median time of recovery and associated factors among under-five children with SAM treated at outpatient therapeutic feeding unit in Dire Dawa, Eastern Ethiopia from January 1st, 2013 to December 31st, 2016. METHODS: A facility-based retrospective cohort study supplemented with qualitative inquiry was conducted to analyze the records of 713 under-5 children with SAM that were randomly selected from four health centers and one hospital in Dire Dawa. In-depth interviews were conducted with five health professionals. Data was collected from the nutrition registration log book by using structured check lists. The collected data were entered into EPI-data version 3.1 software and exported to SPSS version 23 for analysis using Kaplan Meir and Cox proportional hazard regression. RESULTS: The overall recovery rate was 569 (79.8%). Eighty (11.2%) defaulted, 27 (3.8%) were non-responders, 4 (0.6%) died and 15 (2.1%) were transferred-out. The median recovery time was 8.7 weeks (IQR: 5.0-14 weeks). Children with an admission weight of ≥7kg (AHR = 1.73, 95% CI: (1.41-2.14), children who were dewormed (AHR = 1.44, 95% CI: (1.01-2.06) and children with weight gain of ≥8g/kg/day (AHR = 5.76, 95% CI: (4.51-7.38) had higher probability of recovering faster. However, marasmic children stayed longer in treatment (AHR = 0.51, 95% CI: (0.37-0.71) and a low Plumpy Nut consumption rate (g/day) (AHR = 0.79) was associated with longer time of stay on treatment. CONCLUSION: The recovery rate was within the level specified in the Sphere International standards which is >75%. A higher weight at admission, taking deworming and a steady weight gain were positively associated with a fast recovery time. Appropriate nutritional therapy and management of SAM as per the national protocol will be helpful to overcome lower weight gain and higher length of stay on treatment.

Alternative Ready-To-Use Therapeutic Food Yields Less Recovery Than the Standard for Treating Acute Malnutrition in Children From Ghana.

BACKGROUND: Only 20% of children with severe acute malnutrition (SAM) have access to ready-to-use therapeutic food (RUTF), and RUTF cost limits its accessibility. METHODS: This randomized, double-blind controlled study involved a clinical equivalence trial comparing the effectiveness of an alternative RUTF with standard RUTF in the home-based treatment of uncomplicated SAM and moderate malnutrition in Ghanaian children aged 6 to 59 months. The primary outcome was recovery, equivalence was defined as being within 5 percentage points of the control group, and an intention-to-treat analysis was used. Alternative RUTF was composed of whey protein, soybeans, peanuts, sorghum, milk, sugar, and vegetable oil. Standard RUTF included peanuts, milk, sugar, and vegetable oil. The cost of alternative RUTF ingredients was 14% less than standard RUTF. Untargeted metabolomics was used to characterize the bioactive metabolites in the RUTFs. RESULTS: Of the 1,270 children treated for SAM or moderate malnutrition, 554 of 628 (88%) receiving alternative RUTF recovered (95% confidence interval [CI]=85% to 90%) and 516 of 642 (80%) receiving standard RUTF recovered (95% CI=77% to 83%). The difference in recovery was 7.7% (95% CI=3.7% to 11.7%). Among the 401 children with SAM, the recovery rate was 130 of 199 (65%) with alternative RUTF and 156 of 202 (77%) with standard RUTF (P=.01). The default rate in SAM was 60 of 199 (30%) for alternative RUTF and 41 of 202 (20%) for standard RUTF (P=.04). Children enrolled with SAM who received alternative RUTF had less daily weight gain than those fed standard RUTF (2.4 ± 2.4 g/kg vs. 2.9 ± 2.6 g/kg, respectively; P<.05). Among children with moderate wasting, recovery rates were lower for alternative RUTF, 386 of 443 (87%), than standard RUTF, 397 of 426 (93%) (P=.003). More isoflavone metabolites were found in alternative RUTF than in the standard. CONCLUSION: The lower-cost alternative RUTF was less effective than standard RUTF in the treatment of severe and moderate malnutrition in Ghana.

Ready-to-use therapeutic food (RUTF) for home-based nutritional rehabilitation of severe acute malnutrition in children from six months to five years of age.

BACKGROUND: Management of severe acute malnutrition (SAM) in children comprises two potential phases: stabilisation and rehabilitation. During the initial stabilisation phase, children receive treatment for dehydration, electrolyte imbalances, intercurrent infections and other complications. In the rehabilitation phase (applicable to children presenting with uncomplicated SAM or those with complicated SAM after complications have been resolved), catch-up growth is the main focus and the recommended energy and protein requirements are much higher. In-hospital rehabilitation of children with SAM is not always desirable or practical - especially in rural settings - and home-based care can offer a better solution. Ready-to-use therapeutic food (RUTF) is a widely used option for home-based rehabilitation, but the findings of our previous review were inconclusive. OBJECTIVES: To assess the effects of home-based RUTF used during the rehabilitation phase of SAM in children aged between six months and five years on recovery, relapse, mortality and rate of weight gain. SEARCH METHODS: We searched the following databases in October 2018: CENTRAL, MEDLINE, Embase, six other databases and three trials registers. We ran separate searches for cost-effectiveness studies, contacted researchers and healthcare professionals in the field, and checked bibliographies of included studies and relevant reviews. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs, where children aged between six months and five years with SAM were, during the rehabilitation phase, treated at home with RUTF compared to an alternative dietary approach, or with different regimens and formulations of RUTF compared to each other. We assessed recovery, deterioration or relapse and mortality as primary outcomes; and rate of weight gain, time to recovery, anthropometrical changes, cognitive development and function, adverse outcomes and acceptability as secondary outcomes. DATA COLLECTION AND ANALYSIS: We screened for eligible studies, extracted data and assessed risk of bias of those included, independently and in duplicate. Where data allowed, we performed a random-effects meta-analysis using Review Manager 5, and investigated substantial heterogeneity through subgroup and sensitivity analyses. For the main outcomes, we evaluated the quality of the evidence using GRADE, and presented results in a 'Summary of findings' table per comparison. MAIN RESULTS: We included 15 eligible studies (n = 7976; effective sample size = 6630), four of which were cluster trials. Eight studies were conducted in Malawi, four in India, and one apiece in Kenya, Zambia, and Cambodia. Six studies received funding or donations from industry whereas eight did not, and one study did not report the funding source.The overall risk of bias was high for six studies, unclear for three studies, and low for six studies. Among the 14 studies that contributed to meta-analyses, none (n = 5), some (n = 5) or all (n = 4) children were stabilised in hospital prior to commencement of the study. One small study included only children known to be HIV-infected, another study stratified the analysis for 'recovery' according to HIV status, while the remaining studies included HIV-uninfected or untested children. Across all studies, the intervention lasted between 8 and 16 weeks. Only five studies followed up children postintervention (maximum of six months), and generally reported on a limited number of outcomes.We found seven studies with 2261 children comparing home-based RUTF meeting the World Health Organization (WHO) recommendations for nutritional composition (referred to in this review as standard RUTF) with an alternative dietary approach (effective sample size = 1964). RUTF probably improves recovery (risk ratio (RR) 1.33; 95% confidence interval (CI) 1.16 to 1.54; 6 studies, 1852 children; moderate-quality evidence), and may increase the rate of weight gain slightly (mean difference (MD) 1.12 g/kg/day, 95% CI 0.27 to 1.96; 4 studies, 1450 children; low-quality evidence), but we do not know the effects on relapse (RR 0.55, 95% CI 0.30 to 1.01; 4 studies, 1505 children; very low-quality evidence) and mortality (RR 1.05, 95% CI 0.51 to 2.16; 4 studies, 1505 children; very low-quality evidence).Two quasi-randomised cluster trials compared standard, home-based RUTF meeting total daily nutritional requirements with a similar RUTF but given as a supplement to the usual diet (213 children; effective sample size = 210). Meta-analysis showed that standard RUTF meeting total daily nutritional requirements may improve recovery (RR 1.41, 95% CI 1.19 to 1.68; low-quality evidence) and reduce relapse (RR 0.11, 95% CI 0.01 to 0.85; low-quality evidence), but the effects are unknown for mortality (RR 1.36, 95% CI 0.46 to 4.04; very low-quality evidence) and rate of weight gain (MD 1.21 g/kg/day, 95% CI - 0.74 to 3.16; very low-quality evidence).Eight studies randomised 5502 children (effective sample size = 4456) and compared standard home-based RUTF with RUTFs of alternative formulations (e.g. using locally available ingredients, containing less or no milk powder, containing specific fatty acids, or with added pre- and probiotics). For recovery, it made little or no difference whether standard or alternative formulation RUTF was used (RR 1.03, 95% CI 0.99 to 1.08; 6 studies, 4188 children; high-quality evidence). Standard RUTF decreases relapse (RR 0.84, 95% CI 0.72 to 0.98; 6 studies, 4188 children; high-quality evidence). However, it probably makes little or no difference to mortality (RR 1.00, 95% CI 0.80 to 1.24; 7 studies, 4309 children; moderate-quality evidence) and may make little or no difference to the rate of weight gain (MD 0.11 g/kg/day, 95% CI -0.32 to 0.54; 6 studies, 3807 children; low-quality evidence) whether standard or alternative formulation RUTF is used. AUTHORS' CONCLUSIONS: Compared to alternative dietary approaches, standard RUTF probably improves recovery and may increase rate of weight gain slightly, but the effects on relapse and mortality are unknown. Standard RUTF meeting total daily nutritional requirements may improve recovery and relapse compared to a similar RUTF given as a supplement to the usual diet, but the effects on mortality and rate of weight gain are not clear. When comparing RUTFs with different formulations, the current evidence does not favour a particular formulation, except for relapse, which is reduced with standard RUTF. Well-designed, adequately powered, pragmatic RCTs with standardised outcome measures, stratified by HIV status, and that include diarrhoea as an outcome, are needed.

Indigenously Prepared Ready-to-use Therapeutic Food (RUTF) in Children with Severe Acute Malnutrition.

OBJECTIVE: To compare efficacy of indigenous Ready-to-use Therapeutic Food (Medical Nutrition Therapy) with Standard Nutrition Therapy in children with Severe acute malnutrition. DESIGN: Two facility-based and two community-based models: (i) Open prospective randomized controlled trial comparing Indigenous Ready-to-use Therapeutic Food (Medical Nutrition Therapy) with Standard Nutrition Therapy; (ii) Only Indigenous Ready-to-use Therapeutic Food (Medical Nutrition Therapy); (iii) Doorstep Child Care Centre; and (iv) Community-based Management of Acute Malnutrition. SETTING: (i) Urban Health Center, Dharavi, Mumbai; (ii) Two day care centers of Non-governmental Organization SNEHA - Mumbai; (iii) Urban slums, M East and L Ward, Mumbai. PARTICIPANTS: 1105 children aged 6-60 months in community or hospital inpatient/ outpatient department diagnosed as Severe Acute Malnutrition by WHO definition. INTERVENTION: All subjects received either Indigenous Ready-to-use Therapeutic Food (Medical Nutrition Therapy) or Standard Nutrition Therapy (protein calorie rich diet) for eight weeks and followed up for next four months. MAIN OUTCOME MEASURES: Mean rate of weight gain (g/kg/day), target weight, change in nutritional status. RESULTS: Rate of weight gain was higher (P<0.05) at 2 weeks on indigenous Ready-to-use Therapeutic Food (Medical Nutrition Therapy) (5.63 g/kg/day) as compared to Standard Nutrition Therapy (3.43 g/kg/day). 61.2% subjects achieved target weight compared to 47.7% controls. At 8 weeks, 82.8% subjects recovered from Severe Acute Malnutrition compared to 19.3% controls (P<0.005). The results obtained in community were comparable to facility-based indigenous Ready-to-use Therapeutic Food (Medical Nutrition Therapy). The morbidity was less in study group at follow-up. CONCLUSIONS: Indigenous Ready-to-use Therapeutic Food (Medical Nutrition Therapy) appeared to be superior to Standard Nutrition Therapy in promoting weight gain in children with Severe Acute Malnutrition.

A reduced-carbohydrate and lactose-free formulation for stabilization among hospitalized children with severe acute malnutrition: A double-blind, randomized controlled trial.

BACKGROUND: Children with medically complicated severe acute malnutrition (SAM) have high risk of inpatient mortality. Diarrhea, carbohydrate malabsorption, and refeeding syndrome may contribute to early mortality and delayed recovery. We tested the hypothesis that a lactose-free, low-carbohydrate F75 milk would serve to limit these risks, thereby reducing the number of days in the stabilization phase. METHODS AND FINDINGS: In a multicenter double-blind trial, hospitalized severely malnourished children were randomized to receive standard formula (F75) or isocaloric modified F75 (mF75) without lactose and with reduced carbohydrate. The primary endpoint was time to stabilization, as defined by the World Health Organization (WHO), with intention-to-treat analysis. Secondary outcomes included in-hospital mortality, diarrhea, and biochemical features of malabsorption and refeeding syndrome. The trial was registered at clinicaltrials.gov (NCT02246296). Four hundred eighteen and 425 severely malnourished children were randomized to F75 and mF75, respectively, with 516 (61%) enrolled in Kenya and 327 (39%) in Malawi. Children with a median age of 16 months were enrolled between 4 December 2014 and 24 December 2015. One hundred ninety-four (46%) children assigned to F75 and 188 (44%) to mF75 had diarrhea at admission. Median time to stabilization was 3 days (IQR 2-5 days), which was similar between randomized groups (0.23 [95% CI -0.13 to 0.60], P = 0.59). There was no evidence of effect modification by diarrhea at admission, age, edema, or HIV status. Thirty-six and 39 children died before stabilization in the F75 and in mF75 arm, respectively (P = 0.84). Cumulative days with diarrhea (P = 0.27), enteral (P = 0.42) or intravenous fluids (P = 0.19), other serious adverse events before stabilization, and serum and stool biochemistry at day 3 did not differ between groups. The main limitation was that the primary outcome of clinical stabilization was based on WHO guidelines, comprising clinical evidence of recovery from acute illness as well as metabolic stabilization evidenced by recovery of appetite. CONCLUSIONS: Empirically treating hospitalized severely malnourished children during the stabilization phase with lactose-free, reduced-carbohydrate milk formula did not improve clinical outcomes. The biochemical analyses suggest that the lactose-free formulae may still exceed a carbohydrate load threshold for intestinal absorption, which may limit their usefulness in the context of complicated SAM. TRIAL REGISTRATION: ClinicalTrials.gov NCT02246296.

MUAC as the sole discharge criterion from community-based management of severe acute malnutrition in Burkina Faso.

The use of mid upper arm circumference (MUAC) measurement to screen and determine eligibility for admission to therapeutic feeding programs has been established, but evidence and programmatic experience to inform guidance on the use of MUAC as a discharge criterion is limited. We present results from a large-scale nutritional program using MUAC for admission and discharge and compare program outcomes and response to treatment when determining eligibility for discharge by proportional weight gain versus discharge by MUAC. The study population included all children admitted to the Ministry of Health therapeutic feeding program supported by Médecins Sans Frontières in northern Burkina Faso from September 2007 to December 2011 (n = 50,841). Recovery was high overall using both discharge criteria, with low risks of death, nonresponse, and transfer to inpatient care and high daily gains in weight, MUAC, weight-for-height Z score, and height. When discharge was made by MUAC only, recovery increased, while all adverse program outcomes and length of stay decreased, with increasing MUAC on admission. MUAC-based programming, where MUAC is integrated into program screening, admission, and discharge, is one of several new approaches that can be used to target resources to the most at-risk malnourished children and improve program efficiency and coherency. This analysis provides additional programmatic experience on the use of MUAC-based discharge criterion, but more work may be needed to inform optimal discharge thresholds across settings.

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.