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.

Maternal-focused interventions to improve infant growth and nutritional status in low-middle income countries: A systematic review of reviews.

BACKGROUND: Small and nutritionally at-risk infants under 6 months (<6m) are a vulnerable group at increased risk of mortality, morbidity, poor growth and sub-optimal development. Current national and international (World Health Organization) management guidelines focus mainly on infants' needs, yet growing evidence suggests that maternal factors also influence infant outcomes. We aimed to inform future guidelines by exploring the impacts of maternal-focused interventions on infant feeding and growth. METHODS: We conducted a systematic review of reviews published since 2008 (PROSPERO, register number CRD 42019141724). We explored five databases and a wide variety of maternal-focused interventions based in low- and middle-income countries. Infant outcomes of interest included anthropometric status, birthweight, infant mortality, breastfeeding and complementary feeding practices. Given heterogenous interventions, we present a narrative synthesis of the extracted data. RESULTS: We included a total of 55 systematic reviews. Numerous maternal interventions were effective in improving infant growth or feeding outcomes. These included breastfeeding promotion, education, support and counselling interventions. Maternal mental health, while under-researched, showed potential to positively impact infant growth. There was also some evidence for a positive impact of: women's empowerment, m-health technologies, conditional cash transfers, water, sanitation and hygiene and agricultural interventions. Effectiveness was increased when implemented as part of a multi-sectoral program. Antenatal supplementation with macronutrient, multiple micronutrients, Vitamin D, zinc, iron folic acid and possibly calcium, iodine and B12 in deficient women, improved birth outcomes. In contrast, evidence for postnatal supplementation was limited as was evidence directly focusing on small and nutritionally at-risk infants; most reviews focused on the prevention of growth faltering. CONCLUSION: Our findings suggest sufficient evidence to justify greater inclusion of mothers in more holistic packages of care for small and nutritionally at-risk infants aged <6m. Context specific approaches are likely needed to support mother-infant dyads and ensure infants survive and thrive.

Antimicrobial and micronutrient interventions for the management of infants under 6 months of age identified with severe malnutrition: a literature review.

BACKGROUND: Infants under 6 months (U6M) contribute a significant proportion of the burden and mortality of severe malnutrition globally. Evidence of underlying aetiology in this population is sparse, but it is known that the group includes ex-preterm and low birthweight (LBW) infants. They represent a unique population given their dependence on breastmilk or a safe, secure alternative. Nutrition agencies and health providers struggle to make programming decisions on which interventions should be provided to this group based upon the 2013 WHO Guidelines for the 'Management of Severe Acute Malnutrition in Infants and Young Children' since there are no published interventional trial data focussed on this population. Interim guidance for this group might be informed by evidence of safety and efficacy in adjacent population groups. METHODOLOGY: A narrative literature review was performed of systematic reviews, meta-analyses and randomised controlled trials of antimicrobial and micronutrient interventions (antibiotics, deworming, vitamin A, vitamin D, iron, zinc, folic acid and oral rehydration solution (ORS) for malnutrition) across the population groups of low birthweight/preterm infants, infants under 6 months, infants and children over 6 months with acute malnutrition or through supplementation to breastfeeding mothers. Outcomes of interest were safety and efficacy, in terms of mortality and morbidity. RESULTS: Ninety-four articles were identified for inclusion within this review. None of these studied interventions exclusively in severely malnourished infants U6M. 64% reported on the safety of studied interventions. Significant heterogeneity was identified in definitions of study populations, interventions provided, and outcomes studied. The evidence for efficacy and safety across population groups is reviewed and presented for the interventions listed. CONCLUSIONS: The direct evidence base for medical interventions for severely malnourished infants U6M is sparse. Our review identifies a specific need for accurate micronutrient profiling and interventional studies of micronutrients and oral fluid management of diarrhoea amongst infants U6M meeting anthropometric criteria for severe malnutrition. Indirect evidence presented in this review may help shape interim policy and programming decisions as well as the future research agenda for the management of infants U6M identified as malnourished.

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.

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.

Follow-up of post-discharge growth and mortality after treatment for severe acute malnutrition (FuSAM study): a prospective cohort study.

BACKGROUND: Management of Severe Acute Malnutrition (SAM) plays a vital role in achieving global child survival targets. Effective treatment programmes are available but little is known about longer term outcomes following programme discharge. METHODS: From July 2006 to March 2007, 1024 children (median age 21.5 months, IQR 15-32) contributed 1187 admission episodes to an inpatient-based SAM treatment centre in Blantyre, Malawi. Long term outcomes, were determined in a longitudinal cohort study, a year or more after initial programme discharge. We found information on 88%(899/1024). RESULTS: In total, 42%(427/1024) children died during or after treatment. 25%(105/427) of deaths occurred after normal programme discharge, >90 days after admission. Mortality was greatest among HIV seropositive children: 62%(274/445). Other risk factors included age <12 months; severity of malnutrition at admission; and disability. In survivors, weight-for-height and weight-for-age improved but height-for-age remained low, mean -2.97 z-scores (SD 1.3). CONCLUSIONS: Although SAM mortality in this setting was unacceptably high, our findings offer important lessons for future programming, policy and research. First is the need for improved programme evaluation: most routine reporting systems would have missed late deaths and underestimated total mortality due to SAM. Second, a more holistic view of SAM is needed: while treatment will always focus on nutritional interventions, it is vital to also identify and manage underlying clinical conditions such as HIV and disability. Finally early identification and treatment of SAM should be emphasised: our results suggest that this could improve longer term as well as short term outcomes. As international policy and programming becomes increasingly focused on stunting and post-malnutrition chronic disease outcomes, SAM should not be forgotten. Proactive prevention and treatment services are essential, not only to reduce mortality in the short term but also because they have potential to impact on longer term morbidity, growth and development of survivors.

Probiotics and prebiotics for severe acute malnutrition (PRONUT study): a double-blind efficacy randomised controlled trial in Malawi.

BACKGROUND: Severe acute malnutrition affects 13 million children worldwide and causes 1-2 million deaths every year. Our aim was to assess the clinical and nutritional efficacy of a probiotic and prebiotic functional food for the treatment of severe acute malnutrition in a HIV-prevalent setting. METHODS: We recruited 795 Malawian children (age range 5 to 168 months [median 22, IQR 15 to 32]) from July 12, 2006, to March 7, 2007, into a double-blind, randomised, placebo-controlled efficacy trial. For generalisability, all admissions for severe acute malnutrition treatment were eligible for recruitment. After stabilisation with milk feeds, children were randomly assigned to ready-to-use therapeutic food either with (n=399) or without (n=396) Synbiotic2000 Forte. Average prescribed Synbiotic dose was 10(10) colony-forming units or more of lactic acid bacteria per day for the duration of treatment (median 33 days). Primary outcome was nutritional cure (weight-for-height >80% of National Center for Health Statistics median on two consecutive outpatient visits). Secondary outcomes included death, weight gain, time to cure, and prevalence of clinical symptoms (diarrhoea, fever, and respiratory problems). Analysis was on an intention-to-treat basis. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN19364765. FINDINGS: Nutritional cure was similar in both Synbiotic and control groups (53.9% [215 of 399] and 51.3% [203 of 396]; p=0.40). Secondary outcomes were also similar between groups. HIV seropositivity was associated with worse outcomes overall, but did not modify or confound the negative results. Subgroup analyses showed possible trends towards reduced outpatient mortality in the Synbiotic group (p=0.06). INTERPRETATION: In Malawi, Synbiotic2000 Forte did not improve severe acute malnutrition outcomes. The observation of reduced outpatient mortality might be caused by bias, confounding, or chance, but is biologically plausible, has potential for public health impact, and should be explored in future studies. FUNDING: Department for International Development (DfID).