Effectiveness of nutrition interventions and approaches used for Management of Moderate Acute Malnutrition in Children of age 6-59 months – A Systematic Review Protocol

Background: In year 2019 approximately 47.0 million children under ve were wasted of which 32.3 million were moderately & remaining 14.3 million were severely wasted. Acute malnutrition has been estimated to be responsible for almost 12.6% of under ve deaths globally. If remained untreated moderate Acute malnutrition (MAM) is likely to progress to Severe Acute Malnutrition (SAM). Both prevention and treatment of MAM are, therefore, likely to improve under-ve survival globally. Therefore, this review aimed in determining the effectiveness of different approaches used for the management of MAM in Children 6-59 months of age in comparison with WHO Protocol for the management of MAM. Methods: Systematic review of Quantitative literature on Management of MAM in children 6-59 months using two electronic data bases (PubMed and Cochrane Library) and search engine (google scholars). Use of Grey literature, manual search and cross referencing were also performed. PRISMA checklist was used as a guide to this review. Total 14 studies out of XXXX were available for full text review based on eligibility criteria. Data extraction sheet was designed to extract relevant information. Overall Quality appraisal of included studies will be undertaken using Joanna Briggs Institute (JBI) checklist for RCTs and New castle checklist for other studies. Data Synthesis will be done using Review Manager software version 5.3. Discussion: Acute malnutrition is a continuum condition, but severe and moderate forms are treated separately This review ndings would expect to explore the effective interventions and approaches undertaken for the management of MAM; in order to support and advocate for uniform, effective, simpler and sustainable approach for its management and to ensure that all MAM children should have access to treatment and hence not been neglected or awaited till the situation deteriorated to SAM.

literature, manual search and cross referencing were also performed. PRISMA checklist was used as a guide to this review. Total 14 studies out of XXXX were available for full text review based on eligibility criteria. Data extraction sheet was designed to extract relevant information. Overall Quality appraisal of included studies will be undertaken using Joanna Briggs Institute (JBI) checklist for RCTs and New castle checklist for other studies. Data Synthesis will be done using Review Manager software version 5.3.
Discussion: Acute malnutrition is a continuum condition, but severe and moderate forms are treated separately This review ndings would expect to explore the effective interventions and approaches undertaken for the management of MAM; in order to support and advocate for uniform, effective, simpler and sustainable approach for its management and to ensure that all MAM children should have access to treatment and hence not been neglected or awaited till the situation deteriorated to SAM. Systematic Review registration: PROSPERO, CRD42020161404 Background Malnutrition remains a signi cant problem of developing countries. Maternal and child undernutrition comprised of Stunting (short height for age), Wasting (low weight for height), Under-weight (low weight for age) and Micronutrient de ciencies or hidden huger (de ciency of essential vitamins and minerals) [1]. Despite of multiple efforts over decades, globally the current burden of malnutrition is still high.
Estimated over 150 million of under ve children are stunted and 50.5 million are wasted (severe and moderate acute malnutrition), these account for 22.2% and 7.5% of total under ve children worldwide [2].
According to UNICEF, WHO and World Bank joint estimates report 2020, in year 2019 approximately 47.0 million children under ve were wasted (6.9% of total under ve children globally) of which 14.3 million were severely wasted (a weight-for-height at −3 Z-scores of median WHO growth standards with visible severe wasting and/or presence of nutritional edema) [3]. More than two thirds (69%) of all wasted children under 5 lived in Asia and more than one quarter (27%) [3] Acute malnutrition has been estimated to be responsible for almost 12.6% of deaths in children under 5 years of age [4], of this Severe Acute Malnutrition (SAM) contributes to 7.4% of the under-5 mortality [4]. South Asia is the home of 32 million acutely malnourished under 5 children higher than any other region, with greatest prevalence in India (26 million), Pakistan (3 million) and Bangladesh (2.2 million) [5].
Among acute malnutrition, the major proportion of children are moderately Acute Malnourished (MAM) (22 million). If they remained untreated due to any reason; MAM is likely to progress to SAM [5]. Both prevention and treatment of MAM are, therefore, likely to improve under-ve survival globally [6] According to key ndings report of National Nutrition Survey, 2018; In Pakistan since 1997, the prevalence of low weight for height among young children is on the rise, from 8.6% in 1997 to 15.1% in 2011 and 17.7% in 2018 [7]. Despite improvements in other socioeconomic indicators, acute malnutrition remains in a state of nutrition emergency. This is the highest rate of wasting in Pakistan's history. [7]; Sindh province have even quite high prevalence of wasting than National gure (23.5% approx.) [7].
According to World Health Organization (WHO) and the United Nations Children's Fund (UNICEF) MAM is de ned as a low weight-for-height between -2 and -3 z-scores of the median WHO growth standards, without oedema [8], or an arm circumference between 115 and125 mm, without oedema in children aged 6 to 59 months [9]. Over decades; Prevention and treatment of MAM demanded the development of specialized food products, including Forti ed Blended Foods (FBFs) [10] and Lipid based Nutrient Supplements (LNS).
Various formulations of Corn Soy Blend (CSB) and Wheat Soy Blend (WSB) have been used for the past ve decades, evolving with the advances in scienti c evidence of their nutritional value and impact [10] (refer table 1).
A review document by Food and Nutrition Technical Assistance; indicated high reliance on specialized food and no standardized approach for the management of MAM [11]. Similar document has delineated interventions used for treatment of MAM in developing countries of South Asia [11] (refer table 2).
The purpose for prescribing nutritional supplements/ therapy in acute malnutrition is to provide macroand micronutrients in relatively large quantities to enable fast recovery. Since infants and children have small body sizes that limit the quantity of food that can be consumed at one time, the supplement must be energy dense and given at frequent intervals to satisfy the dietary need of these children.
In the absence of standard guidelines for the management of uncomplicated MAM and variety of products available and protocol followed for its management, it is important to systematically evaluate the effectiveness of the various approaches used or currently in practice for the management of MAM in children 6-59 months.
One recent Cochrane Review has evaluated the effectiveness and safety of LNS for the treatment of MAM in children 6 to 59 months of age but that is only con ned with Lipid based supplements and doesn't captured any details for alternate approaches other than products like effective behaviour change communication counselling, reliance on indigenous food for its management, or optimizing on integrated preventive package rather than supplementary foods etc.
In addition; specialized supplements for MAM -CSB, Lipid based Nutrient Supplements (LNS), High Energy Biscuits (HBE) are program dependent commodities and have patchy coverage and supply inconsistencies, moreover such commodities also undermined the use and potential of indigenous food obtained through plant sources at highly reasonable cost. Therefore, it is expected that this review will provide insights on wider avenues for Policy makers and program implementers for effective, e cient, simpler and sustainable management of MAM in context of developing countries. Therefore, this review aimed in determine the effectiveness of different nutrition interventions use for the management of MAM in comparison WHO de ned protocol for the management of MAM in children 6-59 months of age.

Methodology
This study is a systematic review of peer-reviewed Quantitative studies from literature on management approaches undertaken for the management of uncomplicated MAM in children 6-59 months of age using. The protocol of this systematic review is registered with 'International Prospective Register for Systematic Review' (PROSPERO) CRD CRD42020161404. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines [13]. It comprised of 27 items checklist (refer annexure 1) to assist author to improve systematic review reporting [13].

Types of Studies
The review will include evidence from randomized controlled trials, both individual and cluster randomized, non-randomized controlled trials, both individual and cluster, which have a comparison group; Controlled before-and-after studies (CBA) and interrupted time series analyses, where allocation to the comparison groups was not carried out by the researchers.
Studies that containing only qualitative data and other forms of secondary studies, Commentaries, editorials, symposiums and conference proceedings will be excluded. The publication date will be restricted last ve years starting from Jan 2014 to the present date (Nov 30 th , 2019).

Types of Participants
Children 6-59 months of age identi ed with MAM using Middle Upper Arm Circumference (MUAC) tape between 115-125mm OR a Weight-for-Height Z-scores (WHZ) between -3 and -2 standards deviations of WHO 2006 child growth standards. Children must be from developing countries. Study participants identi ed with MAM based on the National Centre for Health Statistics (NCHS) references will not be included.

Intervention details
Any nutrition intervention that include therapeutic food, supplementary food, forti ed food or infant young child feeding (IYCF) counselling opted for the Management of MAM in children 6-59 months of age. In addition to intervention, any implementation approaches OR alternate protocols and guidelines adopted for MAM management would be included in this review.

Outcomes
The primary study outcomes include cured or recovery from MAM (based on MUAC ≥ 12.5 cm and change in number of deaths in children 6-59 months due to non-provision of any intervention to children identi ed with MAM. Secondary outcome includes average weight gain, average MUAC gain, average length of stay & non-recovered (refer table 3).

Search Methods
The online electronic databases like Pub Med and Cochrane library and search engine -Google scholars were explored to identify studies exploring different modalities of nutrition interventions for the management of MAM in children of age 6-59 months. The information sources were searched using detailed search strategy. Grey literature like Global data base for Implementation of Nutrition Actions (GINA) and WHO regional data base, manual search and cross referencing were also given equal importance. The search terms were grouped into major concepts of Nutrition interventions, Acute malnutrition and children 6-59 months. Boolean operators "AND" and "OR" were used to combine or exclude keywords in a search, resulting in more focused and productive results (Refer table 4) .

Study selection (Inclusion & Exclusion Criteria)
The PICO criteria (Population, Intervention, Comparison and Outcome) were used for study selection. The studies discussing on nutrition interventions or/and different protocols used for the management of MAM in children of age 6-59 months without medical complications were considered for this review.
Studies conferring other forms of malnutrition (stunting, micronutrient de ciency, obesity), also severe form of acute malnutrition or malnutrition with any sign of medical complications was not be included in this SR. Moreover, studies targeting children less than 6 months of age or children older than 59 months were excluded from this review. The detailed inclusion and exclusion criterion for this review is shown in Table 5.
Database searches initially identi ed a total of 71,717 studies. After deduplication an applying lter for years of publication, English language and human as species; 10,490 studies were available for title screening and were screened by titles. From those screened studies, 128 studies were chosen for abstract review and remaining were dropped as not meeting the eligibility criteria or study objectives. Nineteen studies (N=19) were selected for full text review; however, ve studies were excluded as not capturing the intended outcome hence not considered further; therefore, only fourteen (n=14) studies were selected for this systematic review. (Fig 1 is explaining PRISMA ow diagram for database search of studies).

Data Extraction
Data extraction sheet has been developed considering the review context (Please refer annexure 2). Two authors will independently extract the required relevant information from all the articles (n=14) article available for full text review. Relevant data such as the details of the participants, methods, context, intervention, outcomes, results, Barriers in implementations and ethical concerns with its implementations will be extracted from the included articles. Any discrepancies will be resolved by mutual discussion and consensus Quality Assessment The quality appraisal of selected randomized Control Trail (RCTs) studies will be performed using Joanna Briggs Institute (JBI) checklist for Randomized Control trials (refer annexure 3) [14]. The purpose of using this checklist is to critically appraise the studies in a manner that is reviewer friendly and less time consuming. Whereas quality appraisal for non-randomized and other studies will be conducted using New Castle Ottawa Quality assessment scale checklist (refer annexure 5) [15].
Risk of Bias assessment for RCTs; we will use the Cochrane risk of bias tool [16] which assesses selection bias, performance bias, detection bias, attrition bias and reporting bias. We will rate each component as 'high', 'low', or 'unclear' for each risk of bias component. For non-randomised studies, we will use the Cochrane Effective Practice and Organisation of Care (EPOC) risk of bias criteria (based on additional criteria including similar baseline outcome measurements).

Data Synthesis
If included studies are found to be similar in terms of research question, study design and outcome measures reported, a meta-analysis will be carried out for the assessment of heterogeneity and to obtain a pooled estimate of effect. Where meta-analysis is not possible synthesis will be performed using narrative approach.

Subgroup and Sensitivity Analysis
Depending on time and data availability subgroup analysis will be carried out to assess the effectiveness in children of age category 6-23 months and children from 2-5 years. A sub-group analysis may be carried out to ascertain whether there is a signi cant difference between studies with "No intervention" comparison group and those with an alternative intervention (not CMAM) as a comparison group

Results
In progress     Any Health outcome other than related to nutrition (improved IQ, brain development etc.)

Study design
The review will include evidence from randomized controlled trials, both individual and cluster randomized, non-randomized controlled trials, both individual and cluster, which have a comparison group; Controlled before-and-after studies (CBA) and interrupted time series analyses, where allocation to the comparison groups was not carried out by the researchers.
Secondary literature (reviews), Qualitative study only, Commentaries, editorials, symposiums and conference casecontrol studies, cohort studies, cross-sectional studies, qualitative formative assessment, discussion paper, thesis dissertation papers reviews Proceedings