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In 2014, the Emergency Nutrition Network published a report on the relationship between wasting and stunting. We aim to review evidence generated since that review to better understand the implications for improving child nutrition, health and survival. We conducted a systematic review following PRISMA guidelines, registered with PROSPERO. We identified search terms that describe wasting and stunting and the relationship between the two. We included studies related to children under five from low‐ and middle‐income countries that assessed both ponderal growth/wasting and linear growth/stunting and the association between the two. We included 45 studies. The review found the peak incidence of both wasting and stunting is between birth and 3 months. There is a strong association between the two conditions whereby episodes of wasting contribute to stunting and, to a lesser extent, stunting leads to wasting. Children with multiple anthropometric deficits, including concurrent stunting and wasting, have the highest risk of near‐term mortality when compared with children with any one deficit alone. Furthermore, evidence suggests that the use of mid‐upper‐arm circumference combined with weight‐for‐age Z score might effectively identify children at most risk of near‐term mortality. Wasting and stunting, driven by common factors, frequently occur in the same child, either simultaneously or at different moments through their life course. Evidence of a process of accumulation of nutritional deficits and increased risk of mortality over a child's life demonstrates the pressing need for integrated policy, financing and programmatic approaches to the prevention and treatment of child malnutrition.

Among children with moderate acute malnutrition (MAM) the level of serum cobalamin (SC) and effect of food supplements are unknown. We aimed to assess prevalence and correlates of low SC in children with MAM, associations with hemoglobin and development, and effects of food supplements on SC. A randomized 2 × 2 × 3 factorial trial was conducted in Burkina Faso. Children aged 6 to 23 months with MAM received 500 kcal/d as lipid-based nutrient supplement (LNS) or corn-soy blend (CSB), containing dehulled soy (DS) or soy isolate (SI) and 0%, 20%, or 50% of total protein from milk for 3 months. Randomization resulted in baseline equivalence between intervention groups. Data on hemoglobin and development were available at baseline. SC was available at baseline and after 3 and 6 months. SC was available from 1,192 (74.1%) of 1,609 children at baseline. The mean (±SD) age was 12.6 (±5.0) months, and 54% were females. Low mid-upper arm circumference (MUAC; <125 mm) was found in 80.4% (958) of the children and low weight-for-length z-score (WLZ; <-2) in 70.6% (841). Stunting was seen in 38.2% (456). Only 5.9% were not breastfed. Median (IQR) SC was 188 (137; 259) pmol/L. Two-thirds had SC ≤222 pmol/L, which was associated with lower hemoglobin. After age and sex adjustments, very low SC (<112 pmol/L) was associated with 0.21 (95% CI: 0.01; 0.41, p = 0.04) and 0.24 (95% CI: 0.06; 0.42, p = 0.01) z-score lower fine and gross motor development, respectively. SC data were available from 1,330 (85.9%) of 1,548 children followed up after 3 months and 398 (26.5%) of the 1,503 children after 6 months. Based on tobit regression, accounting for left censored data, and adjustments for correlates of missing data, the mean (95% CI) increments in SC from baseline to the 3- and 6-month follow-up were 72 (65; 79, p < 0.001) and 26 (16; 37, p < 0.001) pmol/L, respectively. The changes were similar among the 310 children with SC data at all 3 time points. Yet, the increase was 39 (20; 57, p < 0.001) pmol/L larger in children given LNS compared to CSB if based on SI (interaction, p < 0.001). No effect of milk was found. Four children died, and no child developed an allergic reaction to supplements. The main limitation of this study was that only SC was available as a marker of status and was missing from a quarter of the children. Low SC is prevalent among children with MAM and may contribute to impaired erythropoiesis and child development. The SC increase during supplementation was inadequate. The bioavailability and adequacy of cobalamin in food supplements should be reconsidered. ISRCTN Registry ISRCTN42569496.

Alternative ready‐to‐use therapeutic foods (RUTF) formulations provide an opportunity to lower costs, facilitate local or national ingredient use, and enhance the availability and acceptability of RUTF. This scoping review aimed to identify and categorise the available evidence on alternative RUTF formulations developed and tested globally, assess their compliance with international standards and summarise evidence on acceptability, cost, effectiveness, cost‐effectiveness and adverse events, highlighting evidence gaps to guide future research. Searches of three databases and extensive grey literature were conducted covering the period from 1999 to June 2023. Fifty‐four articles, 42 peer‐reviewed articles and 12 grey literature sources were included. Fifty‐three RUTF formulations at various development stages for the treatment of severe acute malnutrition (SAM) without medical complications in children 6–59 months were identified. Numerous ingredients have undergone testing to replace primarily peanuts and/or milk, demonstrating consistent acceptance and promising results in terms of effectiveness. Evidence on outcomes beyond anthropometric recovery, such as higher iron status, and effects on cognitive and developmental outcomes or gut microbiome, is also limited. Few studies evaluated the cost implications, revealing potential savings in production costs while no significant differences were found in terms of safety. Additional evidence is required on how reduced or milk‐free formulations within the innovation and novel categories can achieve compliance with the required protein digestibility‐corrected amino acid score (PDCAAS) recommendations. Further research is also needed with specific focus on outcomes beyond anthropometric recovery such as cost‐effectiveness, accessibility, macro and micronutrient deficiencies, sustainability of recovery and longer term health outcomes. This scoping review identified 53 alternative RUTF formulations replacing primarily peanuts and/or milk. Many showed promising results in acceptability and effectiveness, with potential cost savings. Further research is needed on outcomes beyond anthropometric recovery including cost‐effectiveness, safety, accessibility, macro and micronutrient deficiencies, gut microbiome and compliance with international nutritional guidelines, particularly concerning reduced and milk‐free formulations. Summary Despite two decades of ongoing research, the evidence on alternative RUTFs is still limited. While some ingredients effectively replace peanuts or milk, optimising protein quality to meet Codex PDCAAS standards is crucial. Alternative RUTF effectiveness must be assessed beyond anthropometric outcomes. Focus should continue on micronutrient deficiencies, especially for higher iron formulations, cognitive and developmental outcomes and effects on gut microbiome and metabolism. More evidence on cost and safety is also needed, going beyond production costs and including comprehensive adverse event analyses between alternative and standard RUTFs.

Background Acute malnutrition treatment coverage remains low worldwide, causing significant morbidity and mortality. Decentralisation of treatment to Community Health Worker (CHW) sites has shown to be an effective strategy to improve access and increase coverage, but evidence on the cost and cost-effectiveness of this approach as well the use of simplified treatment protocols in conflict settings is lacking. The objective of this study was to determine cost per child treated as well as the cost-effectiveness of the hybrid model of treatment delivery (where treatment is provided at both health facilities and CHW sites) using either a standard protocol (Intervention 1) or simplified protocol (Intervention 2) compared to standard treatment at health facilities only (Control) in the conflict affected region of Gao in Northern Mali. Methods This economic evaluation was part of a three-arm cluster randomized controlled trial which enrolled 2038 children with moderate and severe acute malnutrition. Outcomes assessed were cost per child treated as well as average and incremental cost-effectiveness ratios for cost per child cured and disability adjusted life year (DALY) averted. A within study trial horizon, from March 2020 to July 2021, was used. Cost data were collected from accountancy records and through key informant interviews using a societal perspective. Treatment admission and outcome data were obtained from the main trial. Results In the base case scenario the cost per child treated was 272 US$, 179 US$ and 210US$ in the Control, Intervention 1 and 2 groups, respectively. Cost per child cured was 356 US$ in the Control, 219 US$ in the Intervention 1 and 226 US$ Intervention 2 groups. Ready-to-use therapeutic foods (RUTF) costs among SAM children treated with a simplified protocol were 5.7 US$ less per child. The average cost per DALY averted was 173.1 US$ in the Control compared to 60.3 US$ in the Intervention 1 and 53 US$ in the Intervention 2. Conclusion This study shows that involving CHWs in acute malnutrition treatment reduces the cost per child treated and is a cost-effective strategy, due to lower treatment costs and greater coverage in the decentralised model. Switching to a simplified protocol in a conflict setting can lead to cost savings particularly in terms of RUTF, and should be considered where weight-based admission, monitoring or dosage is not possible or RUTF stocks are running low. Trial registration The study protocol was registered under reference ISRCTN-60,973,756 on the 15th of October 2020.

Children with moderate acute malnutrition (MAM) are treated with lipid-based nutrient supplement (LNS) or corn-soy blend (CSB). We assessed the effectiveness of (a) matrix, i.e., LNS or CSB, (b) soy quality, i.e., soy isolate (SI) or dehulled soy (DS), and (c) percentage of total protein from dry skimmed milk, i.e., 0%, 20%, or 50%, in increasing fat-free tissue accretion. Between September 9, 2013, and August 29, 2014, a randomised 2 × 2 × 3 factorial trial recruited 6- to 23-month-old children with MAM in Burkina Faso. The intervention comprised 12 weeks of food supplementation providing 500 kcal/day as LNS or CSB, each containing SI or DS, and 0%, 20%, or 50% of protein from milk. Fat-free mass (FFM) was assessed by deuterium dilution technique. By dividing FFM by length squared, the primary outcome was expressed independent of length as FFM index (FFMI) accretion over 12 weeks. Other outcomes comprised recovery rate and additional anthropometric measures. Of 1,609 children, 4 died, 61 were lost to follow-up, and 119 were transferred out due to supplementation being switched to non-experimental products. No children developed allergic reaction. At inclusion, 95% were breastfed, mean (SD) weight was 6.91 kg (0.93), with 83.5% (5.5) FFM. In the whole cohort, weight increased 0.90 kg (95% CI 0.88, 0.93; p < 0.01) comprising 93.5% (95% CI 89.5, 97.3) FFM. As compared to children who received CSB, FFMI accretion was increased by 0.083 kg/m2 (95% CI 0.003, 0.163; p = 0.042) in those who received LNS. In contrast, SI did not increase FFMI compared to DS (mean difference 0.038 kg/m2; 95% CI -0.041, 0.118; p = 0.35), irrespective of matrix. Having 20% milk protein was associated with 0.097 kg/m2 (95% CI -0.002, 0.196) greater FFMI accretion than having 0% milk protein, although this difference was not significant (p = 0.055), and there was no effect of 50% milk protein (0.049 kg/m2; 95% CI -0.047, 0.146; p = 0.32). There was no effect modification by season, admission criteria, or baseline FFMI, stunting, inflammation, or breastfeeding (p > 0.05). LNS compared to CSB resulted in 128 g (95% CI 67, 190; p < 0.01) greater weight gain if both contained SI, but there was no difference between LNS and CSB if both contained DS (mean difference 22 g; 95% CI -40, 84; p = 0.49) (interaction p = 0.017). Accordingly, SI compared to DS increased weight by 89 g (95% CI 27, 150; p = 0.005) when combined with LNS, but not when combined with CSB. A limitation of this and other food supplementation trials is that it is not possible to collect reliable data on individual adherence. Based on this study, children with MAM mainly gain fat-free tissue when rehabilitated. Nevertheless, LNS yields more fat-free tissue and higher recovery rates than CSB. Moreover, current LNSs with DS may be improved by shifting to SI. The role of milk relative to soy merits further research. ISRCTN registry ISRCTN42569496.

Lipid-based nutrient supplements (LNS) and corn-soy blends (CSBs) with varying soy and milk content are used in treatment of moderate acute malnutrition (MAM). We assessed the impact of these supplements on child development. We conducted a randomised 2 × 2 × 3 factorial trial to assess the effectiveness of 12 weeks' supplementation with LNS or CSB, with either soy isolate or dehulled soy, and either 0%, 20%, or 50% of protein from milk, on child development among 6-23-month-old children with MAM. Recruitment took place at 5 health centres in Province du Passoré, Burkina Faso between September 2013 and August 2014. The study was fully blinded with respect to soy quality and milk content, while study participants were not blinded with respect to matrix. This analysis presents secondary trial outcomes: Gross motor, fine motor, and language development were assessed using the Malawi Development Assessment Tool (MDAT). Of 1,609 children enrolled, 54.7% were girls, and median age was 11.3 months (interquartile range [IQR] 8.2-16.0). Twelve weeks follow-up was completed by 1,548 (96.2%), and 24 weeks follow-up was completed by 1,503 (93.4%); follow-up was similar between randomised groups. During the study, 4 children died, and 102 children developed severe acute malnutrition (SAM). There was no difference in adverse events between randomised groups. At 12 weeks, the mean MDAT z-scores in the whole cohort had increased by 0.33 (95% CI: 0.28, 0.37), p < 0.001 for gross motor; 0.26 (0.20, 0.31), p < 0.001 for fine motor; and 0.14 (0.09, 0.20), p < 0.001 for language development. Children had larger improvement in language z-scores if receiving supplements with milk (20%: 0.09 [-0.01, 0.19], p = 0.08 and 50%: 0.11 [0.01, 0.21], p = 0.02), although the difference only reached statistical significance for 50% milk. Post hoc analyses suggested that this effect was specific to boys (interaction p = 0.02). The fine motor z-scores were also improved in children receiving milk, but only when 20% milk was added to CSB (0.18 [0.03, 0.33], p = 0.02). Soy isolate over dehulled soy increased language z-scores by 0.07 (-0.01, 0.15), p = 0.10, although not statistically significant. Post hoc analyses suggested that LNS benefited gross motor development among boys more than did CSB (interaction p = 0.04). Differences between supplement groups did not persist at 24 weeks, but MDAT z-scores continued to increase post-supplementation. The lack of an unsupplemented control group limits us from determining the overall effects of nutritional supplementation for children with MAM. In this study, we found that child development improved during and after supplementation for treatment of MAM. Milk protein was beneficial for language and fine motor development, while suggested benefits related to soy quality and supplement matrix merit further investigation. Supplement-specific effects were not found post-intervention, but z-scores continued to improve, suggesting a sustained overall effect of supplementation. ISRCTN42569496.

Background Moderate acute malnutrition (MAM) affects millions of children, increasing their risk of dying from infections. Thymus atrophy may be a marker of malnutrition-associated immunodeficiency, but factors associated with thymus size in children with MAM are unknown, as is the effect of nutritional interventions on thymus size. Methods Thymus size was measured by ultrasound in 279 children in Burkina Faso with MAM, diagnosed by low mid-upper arm circumference (MUAC) and/or low weight-for-length z -score (WLZ), who received 12 weeks treatment with different food supplements as part of a randomized trial. Correlates of thymus size and of changes in thymus size after treatment, and after another 12 weeks of follow-up were identified. Results Thymus size correlated positively with age, anthropometry and blood haemoglobin, and was smaller in children with malaria. Children with malnutrition diagnosed using MUAC had a smaller thymus than children diagnosed based on WLZ. Thymus size increased during and after treatment, similarly across the different food supplement groups. Conclusions In children with MAM, the thymus is smaller in children with anaemia or malaria, and grows with recovery. Assuming that thymus size reflects vulnerability, low MUAC seems to identify more vulnerable children than low WLZ in children with MAM. Impact Thymus atrophy is known to be a marker of the immunodeficiency associated with malnutrition in children. In children with moderate malnutrition, we found the thymus to be smaller in children with anaemia or malaria. Assuming that thymus size reflects vulnerability, low MUAC seems to identify more vulnerable children than low weight for length. Thymus atrophy appears reversible with recovery from malnutrition, with similar growth seen in children randomized to treatment with different nutritional supplements.

Treatment outcomes for acute malnutrition can be improved by integrating treatment into community case management (iCCM). However, little is known about the cost‐effectiveness of this integrated nutrition intervention. The present study investigates the cost‐effectiveness of treating moderate acute malnutrition (MAM) through community health volunteer (CHV) and integrating it with routine iCCM. A cost‐effectiveness model compared the costs and effects of CHV sites plus health facility‐based treatment (intervention) with the routine health facility‐based treatment strategy alone (control). The costing assessments combined both provider and patient costs. The cost per DALY averted was the primary metric for the comparison, on which sensitivity analysis was performed. Additionally, the integrated strategy's relative value for money was evaluated using the most recent country‐specific gross domestic product threshold metrics. The intervention dominated the health facility‐based strategy alone on all computed cost‐effectiveness outcomes. MAM treatment by CHVs plus health facilities was estimated to yield a cost per death and DALY averted of US $ 8743 and US$397, respectively, as opposed to US $ 13,846 and US$637 in the control group. The findings also showed that the intervention group spent less per child treated and recovered than the control group: US $ 214 versus US$270 and US $ 306 versus US$485, respectively. Compared with facility‐based treatment, treating MAM by CHVs and health facilities was a cost‐effective intervention. Additional gains could be achieved if more children with MAM are enrolled and treated. Key messages Treatment of MAM by CHVs and health facilities involved a lower cost compared with the health facility‐based treatment approach alone. Treatment of MAM by CHVs and health facilities was cost‐effective compared with the health facility‐based treatment approach alone. Greater health and economic gains could be realized if more children with MAM are enrolled and treated by CHVs through the integration of acute malnutrition treatment into iCCM.

Children with moderate acute malnutrition (MAM) are treated based on low weight-for-length z-score (WLZ), low mid-upper arm circumference (MUAC) or both. This study aimed to assess associations of admission criteria and body composition (BC), to improve treatment of MAM. We undertook a cross-sectional study among 6–23 months old Burkinabe children with MAM. Fat-free (FFM) and fat mass (FM) were determined by deuterium dilution and expressed as FFM (FFMI) and FM index (FMI). Of 1,489 children, 439 (29.5%) were recruited by low MUAC only (MUAC-O), 734 (49.3%) by low WLZ and low MUAC (WLZ-MUAC) and 316 (21.2%) by low WLZ only (WLZ-O). Thus, 1,173 (78.8%) were recruited by low MUAC, with or without low WLZ (ALL-MUAC). After adjustments, WLZ-O had 89 g (95% confidence interval (CI) 5; 172) lower FFM compared to MUAC-O. Similarly, WLZ-O had 0.89 kg/m 2 (95% CI 0.77; 1.01) lower FFMI compared to MUAC-O, whereas there was no difference for FMI. However, boys included by WLZ-O compared to MUAC-O had 0.21 kg/m 2 (95% CI 0.05; 0.38) higher FMI. In contrast, girls included by WLZ-O had 0.17 (95% CI 0.01; 0.33) kg/m 2 lower FMI compared to MUAC-O (interaction, p = 0.002). We found that different criteria for admission into MAM treatment programmes select children with differences in BC, especially FFMI. Trial registration : ISRCTN42569496.

Background Only a small percentage of children with severe and moderate acute malnutrition receive treatment due to resource limitations, relatively complex treatment protocols, persistent supply chain challenges, and limited early identification among high-risk populations. Several innovations to the current model of care for uncomplicated acute malnutrition have been proposed, including modified doses of nutritional supplementation and family-led mid-upper-arm circumference (MUAC) and edema screening (“Family MUAC”) for early identification. The evidence base for these innovations remains limited. Methods The Modified Dosages for Acute Malnutrition (MODAM) study includes three integrated individually randomized clinical trials testing innovations in the identification and treatment of acute malnutrition in Ethiopia. One trial will enroll 2400 children aged 6–59 months with severe acute malnutrition, testing standard weight-based dosing of ready-to-use therapeutic food (RUTF) against two experimental RUTF dosing regimens: either two sachets (1000 kcal) daily of RUTF until discharge, or two sachets until achieving anthropometric criteria for moderate acute malnutrition (MAM), at which time dosing will be decreased to one sachet (500 kcal) daily until discharge as fully recovered. A second trial will enroll 2400 children with MAM and test a standard dose of one daily sachet (540 kcal) of ready-to-use supplemental food against two experimental dosing regimes: one sachet (500 kcal) or two sachets (1000 kcal) of RUTF daily until discharge. Children who recover from these two trials will be randomized again into a third trial evaluating post-recovery protocols designed for the early identification of relapse: (1) the control arm involving one scheduled return visit at 24 weeks post-recovery; (2) the first intervention arm involving three scheduled return visits at 4, 12, and 24 weeks post-recovery; and (3) the second intervention arm which involves caregivers receiving Family MUAC training and one scheduled visit at 24 weeks post-recovery. Discussion This study will provide data on the effectiveness of multiple innovations in the management of childhood acute malnutrition. Results will add to the evidence base on the effectiveness and cost-effectiveness of such modifications in the identification and management of acute malnutrition, ideally adding to the global database on this topic and directly contributing to future WHO guidelines. Trial registration Trials were registered on clinicaltrials.gov as NCT06038071 (registered September 8, 2023), NCT06056089 (registered September 20, 2023), and NCT06061484 (registered September 24, 2023).