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.

Post-Recovery Relapse of Children Treated with a Simplified, Combined Nutrition Treatment Protocol in Mali: A Prospective Cohort Study.

The present study aimed to determine the 6-month incidence of relapse and associated factors among children who recovered from acute malnutrition (AM) following mid-upper arm circumference (MUAC)-based simplified combined treatment using the ComPAS protocol. A prospective cohort of 420 children who had reached a MUAC ≥ 125 mm for two consecutive measures was monitored between December 2020 and October 2021. Children were seen at home fortnightly for 6 months. The overall 6-month cumulative incidence of relapse [95%CI] into MUAC < 125 mm and/or edema was 26.1% [21.7; 30.8] and 1.7% [0.6; 3.6] to MUAC < 115 mm and/or edema. Relapse was similar among children initially admitted to treatment with a MUAC < 115 mm and/or oedema and among those with a MUAC ≥ 115 mm but <125 mm. Relapse was predicted by lower anthropometry both at admission to and discharge from treatment, and a higher number of illness episodes per month of follow-up. Having a vaccination card, using an improved water source, having agriculture as the main source of income, and increases in caregiver workload during follow-up all protected from relapse. Children discharged as recovered from AM remain at risk of relapsing into AM. To achieve reduction in relapse, recovery criteria may need to be revised and post-discharge strategies tested.

The management of moderate acute malnutrition in children aged 6-59 months in low- and middle-income countries: a systematic review and meta-analysis.

BACKGROUND: Malnutrition is a leading cause of morbidity and mortality in children aged <5 y, especially in low- and middle-income countries (LMICs). Unlike severe acute malnutrition, moderate acute malnutrition (MAM) affects greater numbers globally, and guidelines lack a robust evidence base. This systematic review and meta-analysis assessed the evidence for lipid-based nutrient supplements (LNSs), fortified blended flours (FBFs) and nutrition counselling, in the treatment of MAM. METHODS: Four databases were systematically searched for studies conducted in LMICs that compared the effectiveness of food-based products with any comparator group in promoting recovery from MAM in children aged 6-59 mo. Where appropriate, pooled estimates of effect were estimated using random-effects meta-analyses. RESULTS: A total of 13 trials were identified for inclusion. All used active controls. There was evidence of increased probability of recovery (gaining normal weight-for-height and/or mid-upper arm circumference) among children treated with LNSs compared with children treated with FBFs (risk ratio 1.05, 95% CI 1.01 to 1.09, p=0·009). CONCLUSION: Based on a relatively small number of studies mainly from Africa, LNSs are superior to FBFs in improving anthropometric recovery from MAM. Current evidence for the use of food supplements in MAM treatment is based on comparisons with active controls. Future studies should assess a wider range of comparator groups, such as nutrition education/counselling alone, and outcomes, including body composition, morbidity and development.

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.

The "ComPAS Trial" combined treatment model for acute malnutrition: study protocol for the economic evaluation.

BACKGROUND: Acute malnutrition is currently divided into severe (SAM) and moderate (MAM) based on level of wasting. SAM and MAM currently have separate treatment protocols and products, managed by separate international agencies. For SAM, the dose of treatment is allocated by the child's weight. A combined and simplified protocol for SAM and MAM, with a standardised dose of ready-to-use therapeutic food (RUTF), is being trialled for non-inferior recovery rates and may be more cost-effective than the current standard protocols for treating SAM and MAM. METHOD: This is the protocol for the economic evaluation of the ComPAS trial, a cluster-randomised controlled, non-inferiority trial that compares a novel combined protocol for treating uncomplicated acute malnutrition compared to the current standard protocol in South Sudan and Kenya. We will calculate the total economic costs of both protocols from a societal perspective, using accounting data, interviews and survey questionnaires. The incremental cost of implementing the combined protocol will be estimated, and all costs and outcomes will be presented as a cost-consequence analysis. Incremental cost-effectiveness ratio will be calculated for primary and secondary outcome, if statistically significant. DISCUSSION: We hypothesise that implementing the combined protocol will be cost-effective due to streamlined logistics at clinic level, reduced length of treatment, especially for MAM, and reduced dosages of RUTF. The findings of this economic evaluation will be important for policymakers, especially given the hypothesised non-inferiority of the main health outcomes. The publication of this protocol aims to improve rigour of conduct and transparency of data collection and analysis. It is also intended to promote inclusion of economic evaluation in other nutrition intervention studies, especially for MAM, and improve comparability with other studies. TRIAL REGISTRATION: ISRCTN 30393230 , date: 16/03/2017.

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.