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.

How age and sex affect treatment outcomes for children with severe malnutrition: A multi-country secondary data analysis.

Age and sex influence the risk of childhood wasting. We aimed to determine if wasting treatment outcomes differ by age and sex in children under 5 years, enroled in therapeutic and supplementary feeding programmes. Utilising data from stage 1 of the ComPAS trial, we used logistic regression to assess the association between age, sex and wasting treatment outcomes (recovery, death, default, non-response, and transfer), modelling the likelihood of recovery versus all other outcomes. We used linear regression to calculate differences in mean length of stay (LOS) and mean daily weight gain by age and sex. Data from 6929 children from Kenya, Chad, Yemen and South Sudan was analysed. Girls in therapeutic feeding programmes were less likely to recover than boys (pooled odds ratio [OR]: 0.84, 95% confidence interval [CI]: 0.72-0.97, p = 0.018). This association was statistically significant in Chad (OR: 0.61, 95% CI: 0.39-0.95, p = 0.030) and Yemen (OR: 0.47, 95% CI: 0.27-0.81, p = 0.006), but not in Kenya and South Sudan. Multinomial analysis, however, showed no difference in recovery between sexes. There was no difference between sexes for LOS, but older children (24-59 months) had a shorter mean LOS than younger children (6-23 months). Mean daily weight gain was consistently lower in boys compared with girls. We found few differences in wasting treatment outcomes by sex and age. The results do not indicate a need to change current programme inclusion requirements or treatment protocols on the basis of sex or age, but future research in other settings should continue to investigate the aetiology of differences in recovery and implications for treatment protocols.

The bioelectrical impedance analysis (BIA) international database: aims, scope, and call for data.

BACKGROUND: Bioelectrical impedance analysis (BIA) is a technique widely used for estimating body composition and health-related parameters. The technology is relatively simple, quick, and non-invasive, and is currently used globally in diverse settings, including private clinicians' offices, sports and health clubs, and hospitals, and across a spectrum of age, body weight, and disease states. BIA parameters can be used to estimate body composition (fat, fat-free mass, total-body water and its compartments). Moreover, raw measurements including resistance, reactance, phase angle, and impedance vector length can also be used to track health-related markers, including hydration and malnutrition, and disease-prognostic, athletic and general health status. Body composition shows profound variability in association with age, sex, race and ethnicity, geographic ancestry, lifestyle, and health status. To advance understanding of this variability, we propose to develop a large and diverse multi-country dataset of BIA raw measures and derived body components. The aim of this paper is to describe the 'BIA International Database' project and encourage researchers to join the consortium. METHODS: The Exercise and Health Laboratory of the Faculty of Human Kinetics, University of Lisbon has agreed to host the database using an online portal. At present, the database contains 277,922 measures from individuals ranging from 11 months to 102 years, along with additional data on these participants. CONCLUSION: The BIA International Database represents a key resource for research on body composition.

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.

How do children with severe underweight and wasting respond to treatment? A pooled secondary data analysis to inform future intervention studies.

Children with weight-for-age z-score (WAZ) <-3 have a high risk of death, yet this indicator is not widely used in nutrition treatment programming. This pooled secondary data analysis of children aged 6-59 months aimed to examine the prevalence, treatment outcomes, and growth trajectories of children with WAZ <-3 versus children with WAZ ≥-3 receiving outpatient treatment for wasting and/or nutritional oedema, to inform future protocols. Binary treatment outcomes between WAZ <-3 and WAZ ≥-3 admissions were compared using logistic regression. Recovery was defined as attaining mid-upper-arm circumference ≥12.5 cm and weight-for-height z-score ≥-2, without oedema, within a period of 17 weeks of admission. Data from 24,829 children from 9 countries drawn from 13 datasets were included. 55% of wasted children had WAZ <-3. Children admitted with WAZ <-3 compared to those with WAZ ≥-3 had lower recovery rates (28.3% vs. 48.7%), higher risk of death (1.8% vs. 0.7%), and higher risk of transfer to inpatient care (6.2% vs. 3.8%). Growth trajectories showed that children with WAZ <-3 had markedly lower anthropometry at the start and end of care, however, their patterns of anthropometric gains were very similar to those with WAZ ≥-3. If moderately wasted children with WAZ <-3 were treated in therapeutic programmes alongside severely wasted children, we estimate caseloads would increase by 32%. Our findings suggest that wasted children with WAZ <-3 are an especially vulnerable group and those with moderate wasting and WAZ <-3 likely require a higher intensity of nutritional support than is currently recommended. Longer or improved treatment may be necessary, and the timeline and definition of recovery likely need review.

Effectiveness of Acute Malnutrition Treatment at Health Center and Community Levels with a Simplified, Combined Protocol in Mali: An Observational Cohort Study.

A simplified, combined protocol was created that admits children with a mid-upper-arm circumference (MUAC) of <125 mm or edema to malnutrition treatment with ready-to-use therapeutic food (RUTF) that involves prescribing two daily RUTF sachets to children with MUAC < 115 mm or edema and one daily sachet to those with 115 mm ≤ MUAC < 125 mm. This treatment was previously shown to result in non-inferior programmatic outcomes compared with standard treatment. We aimed at observing its effectiveness in a routine setting at scale, including via delivery by community health workers (CHWs). A total of 27,800 children were admitted to the simplified, combined treatment. Treatment resulted in a 92% overall recovery, with a mean length of stay of 40 days and a mean RUTF consumption of 62 sachets per child treated. Among children admitted with MUAC < 115 mm or edema, 87% recovered with a mean length of stay of 55 days and consuming an average of 96 RUTF sachets. The recovery in all sub-groups studied exceeded 85%. Treatment by CHWs resulted in a similar (94%) recovery to treatment by formal healthcare workers (92%). The simplified, combined protocol resulted in high recovery and low RUTF consumption per child treated and can safely be adopted by CHWs to provide treatment at the community level.

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.

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.

Relapse and post-discharge body composition of children treated for acute malnutrition using a simplified, combined protocol: A nested cohort from the ComPAS RCT.

INTRODUCTION: Severe and moderate acute malnutrition (SAM and MAM) affect more than 50 million children worldwide yet 80% of these children do not access care. The Combined Protocol for Acute Malnutrition Study (ComPAS) trial assessed the effectiveness of a simplified, combined SAM/MAM protocol for children aged 6-59 months and found non-inferior recovery compared to standard care. To further inform policy, this study assessed post-discharge outcomes of children treated with this novel protocol in Kenya. METHODS: Six 'combined' protocol clinics treated SAM and MAM children using an optimised mid-upper arm circumference (MUAC)-based dose of ready-to-use therapeutic food (RUTF). Six 'standard care' clinics treated SAM with weight-based RUTF rations; MAM with ready-to-use supplementary food (RUSF). Four months post-discharge, we assessed anthropometry, recent history of illness, and body composition by bioelectrical impedance analysis. Data was analysed using multivariable linear regression, adjusted for age, sex and allowing for clustering by clinic. RESULTS: We sampled 850 children (median age 18 months, IQR 15-23); 44% of the original trial sample in Kenya. Children treated with the combined protocol had similar anthropometry, fat-free mass, fat mass, skinfold thickness z-scores, and frequency of common illnesses 4 months post-discharge compared the standard protocol. Mean subscapular skinfold z-scores were close to the global norm (standard care: 0.24; combined 0.27). There was no significant difference in odds of relapse between protocols (SAM, 3% vs 3%, OR = 1.0 p = 0.75; MAM, 10% vs 12%, OR = 0.90 p = 0.34). CONCLUSIONS: Despite the lower dosage of RUTF for most SAM children in the combined protocol, their anthropometry and relapse rates at 4 months post-discharge were similar to standard care. MAM children treated with RUTF had similar body composition to those treated with RUSF and neither group exhibited excess adiposity. These results add further evidence that a combined protocol is as effective as standard care with no evidence of adverse effects post-discharge. A simplified, combined approach could treat more children, stretch existing resources further, and contribute to achieving Sustainable Development Goal Two.

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.

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.