Long-term effects of severe acute malnutrition on growth, body composition, and function; a prospective cohort study in Malawi

Background: Tackling severe acute malnutrition (SAM) is a global health priority. Whilst SAM-related mortality is well described, little is known about long-term effects on survivors. Given extensive evidence from developed countries that early nutritional insults have enduring detrimental effects, particularly heightened risk of non-communicable disease (NCD) in adulthood, it is plausible that SAM survivors could share some of these traits. Applying the DOHaD (Developmental Origins of Health and Disease) concept to a novel group, this study aimed to explore the long-term impacts of SAM on growth, body composition, and functional outcomes. Methods and Findings: From August 2013 to February 2014 I followed-up the 352/1024 Malawian children who were still alive following SAM treatment in 2006-2007, comparing them to siblings and age/sex matched community controls. Compared to community controls, SAMsurvivors had significantly lower height-for-age z-score (HAZ) (-0.4, CI -0.2 to -0.6) and limb length (-2.0cm, CI -1.0 to -3.0) although there was evidence of some catch-up growth. They also had smaller mid-upper arm, calf and hip circumferences and less lean mass. Functional deficits included: weaker hand-grip (-1.68kg, CI -0.9 to -2.4) and fewer minutes completed of an exercise test (-1.59 minutes, CI -1.0 to -2.5). There was no statistically significant impact on lung function, skinfold thickness, sitting height and head circumference. Conclusions: These results show that there are long-term implications of an episode of SAM in the areas of growth, body composition, and physical function. Most notable are deficits in HAZ, lean mass, grip strength, and preservation of sitting height and head circumference at the expense of leg length, a pattern consistent with ‘thrifty growth’ which is associated with increased future cardiometabolic disease risk. Some catch-up of linear growth has occurred, suggesting that interventions post-“first 1000 days” could still be effective. Children who experienced SAM at an older age had greater detrimental effects, emphasising the need for early intervention and better prevention. Further follow-up is required to establish the full impact of puberty, and societal transition such as greater access to high fat/sugar diets. Intervention studies are also needed to determine whether earlier SAM treatment, improved post-SAM care such as nutrition supplementation and/or physical fitness interventions, could minimise or reverse some of these long-term effects

Follow-up between 6 and 24 months after discharge from treatment for severe acute malnutrition in children aged 6-59 months: A systematic review.

BACKGROUND: Severe acute malnutrition (SAM) is a major global health problem affecting some 16.9 million children under five. Little is known about what happens to children 6-24 months post-discharge as this window often falls through the gap between studies on SFPs and those focusing on longer-term effects. METHODS: A protocol was registered on PROSPERO (PROSPERO 2017:CRD42017065650). Embase, Global Health and MEDLINE In-Process and Non-Indexed Citations were systematically searched with terms related to SAM, nutritional intervention and follow-up between June and August 2017. Studies were selected if they included children who experienced an episode of SAM, received a therapeutic feeding intervention, were discharged as cured and presented any outcome from follow-up between 6-24 months later. RESULTS: 3,691 articles were retrieved from the search, 55 full-texts were screened and seven met the inclusion criteria. Loss-to-follow-up, mortality, relapse, morbidity and anthropometry were outcomes reported. Between 0.0% and 45.1% of cohorts were lost-to-follow-up. Of those discharged as nutritionally cured, mortality ranged from 0.06% to 10.4% at an average of 12 months post-discharge. Relapse was inconsistently defined, measured, and reported, ranging from 0% to 6.3%. Two studies reported improved weight-for-height z-scores, whilst three studies that reported height-for-age z-scores found either limited or no improvement. CONCLUSIONS: Overall, there is a scarcity of studies that follow-up children 6-24 months post-discharge from SAM treatment. Limited data that exists suggest that children may exhibit sustained vulnerability even after achieving nutritional cure, including heightened mortality and morbidity risk and persistent stunting. Prospective cohort studies assessing a wider range of outcomes in children post-SAM treatment are a priority, as are intervention studies exploring how to improve post-SAM outcomes and identify high-risk children

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

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

Carer and staff perspectives on supplementary suckling for treating infant malnutrition: qualitative findings from Malawi.

Severe acute malnutrition (SAM) in infants aged <6 months is a major global health problem. Supplementary suckling (SS) is widely recommended as an inpatient treatment technique for infant <6 months SAM. Its aim is to re-establish effective exclusive breastfeeding. Despite widespread support in guidelines, research suggests that field use of SS is limited in many settings. In this study, we aimed therefore to describe and understand the barriers and facilitating factors to SS as a treatment technique for infant SAM. We conducted qualitative interviews and focus group discussions in a hospital setting in Blantyre, Malawi, with ward staff and caregivers of infants <2 years. We created a conceptual framework based on five major themes identified from the data: (1) motivation; (2) breastfeeding views; (3) practicalities; (4) understanding; and (5) perceptions of hospital-based medicine. Within each major theme, more setting-specific subthemes can also be developed. Other health facilities considering SS roll-out could consider their own barriers and facilitators using our framework; this will facilitate the implementation of SS, improve staff confidence and therefore give SS a better chance of success. Used to shape and guide discussions and inform action plans for implementing SS, the framework has the potential to facilitate SS roll-out in settings other than Malawi, where this study was conducted. We hope that it will help pave the way to more widespread SS, more research into its use and effectiveness, and a stronger evidence-base on malnutrition in infants aged <6 months

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

Nutritional status of school-age children and adolescents in eastern and southern Africa: A scoping review

Aims: This review aims to summarize available literature on the nutritional status of school-age children (SAC) and adolescents aged 5-19 years in Eastern and Southern Africa (ESA) and interventions aiming to tackle malnutrition in this age group. Methods: We searched Pubmed, Cochrane Database of Systematic Reviews, Web of Science, Africa Wide Information, ArticleFirst, Biomed Central, BioOne, BIOSIS, CINAHL, EBSCOHost, JSTOR, ProQuest, Google Scholar, SAGE Reference Online, Scopus, ScienceDirect, SpringerLink, Taylor &amp; Francis, and Wiley Online for articles published between 2005 and 2020 according to eligibility criteria. Results: A total of 129 articles were included, with the majority of studies presenting data from Ethiopia (N = 46) and South Africa (N=38). The prevalence of overweight and obesity ranged between 9.1 – 32.3 % and 0.8 – 21.7 % respectively across countries in ESA. Prevalence of thinness, stunting and underweight ranged as follows: 3.0 – 36.8 %; 6.6 – 57.0 %; 5.8 – 27.1 %. Prevalence of anemia was between 13.0 – 76.9 % across the region. There was a dearth of data on other micronutrient deficiencies. There was limited evidence from intervention studies (N = 6), with half of the interventions targeting anemia or iron deficiency using iron supplementation or fortification methods and reporting no significant effect on anemia prevalence. Interventions targeting stunting and thinness (N = 3) reported beneficial effects of providing vitamin A fortified maize, iron supplementation and nutrition education. Conclusions: A triple burden of malnutrition underlines the need to prioritize implementation of double-duty interventions for SAC and adolescents in ESA. Key data gaps included either limited or a lack of data for the majority of countries, especially on micronutrient deficiencies and a scarcity of intervention studies. Greater investment in nutrition research amongst this population is needed to strengthen the evidence base and inform policies and programs to improve nutritional status amongst SAC and adolescents in ESA

Use of Mid-Upper Arm Circumference by Novel Community Platforms to Detect, Diagnose, and Treat Severe Acute Malnutrition in Children: A Systematic Review.

BACKGROUND: A stubborn persistence of child severe acute malnutrition (SAM) and continued gaps in program coverage have made identifying methods for expanding detection, diagnosis, and treatment of SAM an urgent public health need. There is growing consensus that making mid-upper arm circumference (MUAC) use more widely accessible among caregivers and community health workers (CHWs) is an important next step in further decentralizing SAM care and increasing program coverage, including the ability of CHWs to treat uncomplicated SAM in community settings. METHODS: We conducted a systematic review to summarize published and operational evidence published since 2000 describing the use of MUAC for detection and diagnosis of SAM in children aged 6-59 months by caregivers and CHWs, and of management of uncomplicated SAM by CHWs, all outside of formal health care settings. We screened 1,072 records, selected 43 records for full-text screening, and identified 22 studies that met our eligibility criteria. We extracted data on a number of items, including study design, strengths, and weaknesses; intervention and control; and key findings and operational lessons. We then synthesized the qualitative findings to inform our conclusions. The issue of treating children classified as SAM based on low weight-for-height, rather than MUAC, at household level, is not addressed in this review. FINDINGS: We found evidence that caregivers are able to use MUAC to detect SAM in their children with minimal risk and many potential benefits to early case detection and coverage. We also found evidence that CHWs are able to correctly use MUAC for SAM detection and diagnosis and to provide a high quality of care in the treatment of uncomplicated SAM when training, supervision, and motivation are adequate. However, the number of published research studies was small, their geographic scope was narrow, and most described intensive, small-scale interventions; thus, findings are not currently generalizable to public-sector health care systems. CONCLUSIONS: Scaling up the use of MUAC by caregivers and CHWs to detect SAM in household and community settings is a promising step toward improving the coverage of SAM detection, diagnosis, and treatment. Further research on scalability, applicability across a wider range of contexts, coverage impact, and cost is needed. The primary use of MUAC for SAM detection should also be explored where appropriate