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The World Health Organization's 2023 recommendations for managing moderate wasting provide criteria for prioritizing children to receive specially formulated foods (SFF) rather than counseling alone. However, the practical programmatic impact of such prioritization is unclear. This secondary analysis aimed to describe the caseload and treatment outcomes among moderately wasted 6‐ to 59‐month‐old Malian children, categorized into higher‐priority (HP) and lower‐priority (LP) groups. All children admitted with a MUAC ≥ 115 to < 125 mm without nutritional edema received SFF (500 kcal/day) until they achieved a MUAC ≥ 125 mm for 2 consecutive visits. HP criteria were < 2 years old, WAZ < −3 SD, or MUAC 115–119 mm; LP criteria were ≥ 2 years, WAZ ≥ −3 SD, or MUAC ≥ 120 mm. We reported the caseload per priority criterion and compared treatment outcomes, including recovery and anthropometric changes, between LP and HP children. Of the 35 685 children included in the analysis, 95% met at least one priority criterion. The proportion of children recovered was similar between LP and HP children, regardless of the criterion used. MUAC‐for‐age z‐score and WAZ weekly changes showed similar trajectories. Furthermore, although classified as LP, children > 2 years exhibited lower WAZ throughout treatment compared to children < 2 years. Most moderately wasted children (MUAC < 125 mm) met at least one priority criterion, raising concerns about the feasibility and rationale of the prioritization approach. The similar recovery rates in higher‐ and lower‐priority groups after both received SFF highlight the need for research to assess the impact of different interventions. The WHO 2023 anthropometric and age‐based prioritization criteria for moderate wasting classify most of the children as high priority in a MUAC‐based enrollment protocol for wasting treatment. Given the limited selectivity of these criteria, alongside the increased complexity they introduce, their added value for programmatic decision‐making remains uncertain. Evidence is needed to inform optimal implementation of the prioritization criteria and to understand whether different treatment approaches yield differential outcomes for children categorized as high‐ versus low‐priority.

HIV infection affects up to 30% of children presenting with severe acute malnutrition (SAM) in Africa and is associated with increased mortality. Children with SAM are treated similarly regardless of HIV status, although mechanisms of nutritional recovery in HIV and/or SAM are not well understood. We performed a secondary analysis of a clinical trial and plasma proteomics data among children with complicated SAM in Kenya and Malawi. Compared to children with SAM without HIV (n = 113), HIV-infected children (n = 54) had evidence (false discovery rate (FDR) corrected p < 0.05) of metabolic stress, including enriched pathways related to inflammation and lipid metabolism. Moreover, we observed reduced plasma levels of zinc-α-2-glycoprotein, butyrylcholinesterase, and increased levels of complement C2 resembling findings in metabolic syndrome, diabetes and other non-communicable diseases. HIV was also associated (FDR corrected p < 0.05) with higher plasma levels of inflammatory chemokines. Considering evidence of biomarkers of metabolic stress, it is of potential concern that our current treatment strategy for SAM regardless of HIV status involves a high-fat therapeutic diet. The results of this study suggest a need for clinical trials of therapeutic foods that meet the specific metabolic needs of children with HIV and SAM.

Severe acute malnutrition (SAM) constitutes a substantial burden in African hospitals. Despite adhering to international guidelines, high inpatient mortality rates persist and the underlying contributing factors remain poorly understood. We evaluated the 10-year trend (2011-2021) in clinical factors and outcomes among children with severe wasting and/or nutritional edema at Malawi's largest nutritional rehabilitation unit (NRU). This retrospective study analyzed trends in presentation and outcomes using generalized additive models. The association between clinical characteristics and mortality or readmission was examined and key features were also related to time to either mortality or discharge. 1497 children (53%, females) were included. Median age at admission (23 months, IQR 14, 34) or anthropometry (i.e., weight-for-age, height-for-age and weight-for-height) did not change over the 10-years. But the prevalence of edema decreased by 40% whereas dehydration, difficulty breathing, and pallor became more common. Yearly HIV testing increased but positive-detection remained around 11%. Reporting of complete vaccination dropped by 49%, and no reduction in 'watch' antibiotic usage was detected. Overall admissions declined but mortality remained around 23% [95%CI; 21, 25], and deaths occurred earlier (5.6 days [95%CI; 4.6, 6.9] in 2011 vs. 3.5 days [95%CI; 2.5, 4.7] in 2021; p<0.001). Duration of hospitalization was shortened and readmissions surged from 4.9% [95%CI; 3.3, 7.4] in 2011 to 25% [95%CI; 18, 33] in 2021 (p<0.001). Age, wasting, having both dehydration and diarrhea, or having vomiting, cough, or difficulty breathing were associated with mortality but these associations did not show any interaction over time. Over 10 years, mortality risk remained high among hospitalized children with SAM and coincided with worsened clinical presentation at admission and increased readmission. Longitudinal data from major NRUs can identify shifts in clinical profiles or outcomes, and this information can be leveraged to promote earlier care-seeking, improved risk stratification, and implementation of more patient-centered treatments.

Ready-to-use therapeutic foods (RUTFs) have successfully promoted recovery from severe wasting and increased treatment coverage. However, RUTFs do not sufficiently improve linear growth, leaving many survivors of severe wasting at risk of persistent stunting, which is associated with high mortality risk, poor child development and non-communicable diseases in adulthood. High protein quantity and quality can stimulate linear growth. The trial aims to assess whether higher-protein-RUTF leads to higher concentrations of markers of linear growth compared to standard RUTF among 6-23 months old children with severe wasting. We designed a higher protein quantity and quality RUTF for a proof-of-concept (PoC) double-blind randomized controlled trial. These findings will help in informing the potential impact of increased protein in RUTF on linear growth when treating severe wasting towards conducting a larger clinical trial.

Background Despite adherence to WHO guidelines, inpatient mortality among sick children admitted to hospital with complicated severe acute malnutrition (SAM) remains unacceptably high. Several studies have examined risk factors present at admission for mortality. However, risks may evolve during admission with medical and nutritional treatment or deterioration. Currently, no specific guidance exists for assessing daily treatment response. This study aimed to determine the prognostic value of monitoring clinical signs on a daily basis for assessing mortality risk during hospitalization in children with SAM. Methods This is a secondary analysis of data from a randomized trial (NCT02246296) among 843 hospitalized children with SAM. Daily clinical signs were prospectively collected during ward rounds. Multivariable extended Cox regression using backward feature selection was performed to identify daily clinical warning signs (CWS) associated with time to death within the first 21 days of hospitalization. Predictive models were subsequently developed, and their prognostic performance evaluated using Harrell’s concordance index (C-index) and time-dependent area under the curve (tAUC). Results Inpatient case fatality ratio was 16.3% ( n =127). The presence of the following CWS during daily assessment were found to be independent predictors of inpatient mortality: symptomatic hypoglycemia, reduced consciousness, chest indrawing, not able to complete feeds, nutritional edema, diarrhea, and fever. Daily risk scores computed using these 7 CWS together with MUAC<10.5cm at admission as additional CWS predict survival outcome of children with SAM with a C-index of 0.81 (95% CI 0.77–0.86). Moreover, counting signs among the top 5 CWS (reduced consciousness, symptomatic hypoglycemia, chest indrawing, not able to complete foods, and MUAC<10.5cm) provided a simpler tool with similar prognostic performance (C-index of 0.79; 95% CI 0.74–0.84). Having 1 or 2 of these CWS on any day during hospitalization was associated with a 3 or 11-fold increased mortality risk compared with no signs, respectively. Conclusions This study provides evidence for structured monitoring of daily CWS as recommended clinical practice as it improves prediction of inpatient mortality among sick children with complicated SAM. We propose a simple counting-tool to guide healthcare workers to assess treatment response for these children. Trial registration NCT02246296

Background Although mortality risk associated with HIV is well described, HIV-exposed uninfected (HEU) young children are also at increased risk of hospitalization and death as compared to HIV-unexposed uninfected (HUU) children. The drivers of poor outcomes among HEU children remain unknown, limiting the development of interventions to support this vulnerable population. Methods We performed a secondary analysis of data from a large multi-country prospective cohort [Childhood Acute Illness and Nutrition (CHAIN) Network] study. Data from 5 sites in Uganda, Kenya, and Malawi were included. Hospitalized children aged 2–23 months were followed from an index admission for 6 months after discharge to determine acute and long-term outcomes. Using perinatal HIV exposure (HEU and HUU) as the primary exposure and adjusting for child, caregiver, and household characteristics, we compared inpatient and 30-day survival outcomes, nutritional status, hospital length of stay, illness severity, and utilization of inpatient resources. Results We included 1486 children: 217 HEU and 1269 HUU. HEU children had an increased risk of mortality both during hospitalization [adjusted OR 1.96, 95% CI (1.14–3.37)] and in the 30 days following hospital admission [adjusted hazard ratio 2.20, 95% CI (1.10–4.42)]. Wasting and stunting were more frequent in HEU than HUU children, with adjusted OR 1.41, 95% CI (1.03–1.95) and adjusted OR 1.91, 95% CI (1.34–2.70), respectively. HEU children were also more likely to have a prolonged hospital stay compared to HUU children [adjusted OR 1.58, 95% CI (1.08–2.29)], although admission diagnoses, illness severity at admission, and use of inpatient resources (supplemental oxygen, nasogastric tube, and second-line antibiotics) did not differ significantly between groups. Conclusions HEU children are more likely to die during hospitalization and within 30 days of admission, to be wasted and stunted upon hospital admission, and to require a prolonged hospital stay, as compared to HUU children. Hospitals in settings with a high prevalence of women-living-with-HIV should ensure that maternal HIV status is established among children requiring admission and build capacity to provide additional hospital monitoring and early post-discharge support for HEU children.

Children with severe acute malnutrition (SAM) remain vulnerable after treatment at nutritional rehabilitation units (NRUs). The objective was to assess the concurrent pathways in a hypothesized model between caregiver body mass index (BMI), the home environment, and child nutritional status, and development (gross motor, fine motor, language, and social domains) in children with SAM following discharge from inpatient treatment. Structural equation modelling (SEM) was performed with data from a cluster-randomized controlled trial at the Moyo Nutritional Rehabilitation and Research Unit in Blantyre, Malawi. This approach was undertaken to explore simultaneous relationships between caregiver BMI, the home environment (Home Observation for Measurement of the Environment Inventory scores), child nutritional status (anthropometric indicators including weight-for-age z-scores [WAZ]), and child development (Malawi Developmental Assessment Tool (MDAT) z-scores as a latent variable) in children with SAM. These data were collected at participants’ homes six months after discharge from NRU treatment. This analysis included 85 children aged 6–59 months with SAM and their caregivers recruited to the trial at the NRU and followed up successfully six months after discharge. The model with WAZ as the nutritional indicator fit the data according to model fit indices (χ 2 = 28.92, p = 0.42). Caregiver BMI was predictive of better home environment scores (β = 0.23, p = 0.03) and child WAZ (β = 0.30, p = 0.005). The home environment scores were positively correlated with MDAT z-scores (β = 0.32, p = 0.001). Child nutritional status based on WAZ was also correlated with MDAT z-scores (β = 0.37, p<0.001). This study demonstrates that caregiver BMI could ultimately relate to child development in children with SAM, through its links to the home environment and child nutritional status.

Treatment of severe acute malnutrition aims at producing quick catch‐up growth in children to decrease their short‐term mortality risk. The extent to which catch‐up growth is influenced by the amount of energy provided is unclear. This study assessed whether energy provided at admission is associated with catch‐up ponderal growth among children with mid‐upper arm circumference (MUAC) < 115 mm at admission. We conducted a secondary data analysis an operational cohort in Mali. The children were treated with a simplified protocol providing 1000 kcal/day of therapeutic food until MUAC ≥ 115 mm was achieved for two consecutive weeks and 500 kcal/day thereafter until discharge with MUAC ≥ 125 mm for two consecutive weeks. Linear mixed‐effects regression models were fitted to assess the relationship between energy provided at admission (kcal/kg/day) with weight gain velocity (g/kg/day) (primary outcome), change in MUAC ‐for‐age z‐score and change in weight‐for‐age z‐score. Unadjusted models and models adjusted for sex, age, seasonality and MUAC at admission were fitted. Both models included the study site as a random effect. A 10 kcal/kg/day increase in energy provided at admission was associated with increments in all outcomes; for weight gain velocity, the mean (95% CI) increment was 0.340 [0.326, 0.354] g/kg/day and 0.466 [0.446, 0.485] g/kg/day in the unadjusted and adjusted analysis, respectively. A positive relationship exists between energy provided at admission and catch‐up ponderal growth in children with MUAC < 115 mm treated using a simplified protocol. Determining the ideal weight gain rate remains essential for assessing the benefits and risks of increased energy intake during treatment. Among children diagnosed with severe wasting (MUAC < 115 mm), higher provisions of energy at admission (kcal/kg/day) are associated with a higher rate of weight gain, higher changes in weight‐for‐age and MUAC‐for‐age z‐scores. Key messages Among children diagnosed with severe wasting (MUAC < 115 mm), higher provisions of energy at admission (kcal/kg/day) are associated with a higher rate of weight gain, higher changes in weight‐for‐age and MUAC‐for‐age z‐scores. Children treated for severe wasting (MUAC < 115 mm) receiving Ready‐to‐use therapeutic foods (RUTFs) at a dose higher at admission than the WHO 2023 recommendation of 150–185 kcal/kg/day experience higher rates of weight gain and higher changes in weight‐for‐age and MUAC‐for‐age z‐scores. The optimal rate of weight gain in children treated for severe wasting (MUAC < 115 mm) using RUTF remains unknown.

There is scarce data on energy expenditure in ill children with different degrees of malnutrition. This study aimed to determine resting energy expenditure (REE) trajectories in hospitalized malnourished children during and after hospitalization. We followed a cohort of children in Bangladesh and Malawi (2–23 months) with: no wasting (NW); moderate wasting (MW), severe wasting (SW), or edematous malnutrition (EM). REE was measured by indirect calorimetry at admission, discharge, 14-and-45-days post-discharge. 125 children (NW, n = 23; MW, n = 29; SW, n = 51; EM, n = 22), median age 9 (IQR 6, 14) months, provided 401 REE measurements. At admission, the REE of children with NW and MW was 67 (95% CI [58, 75]) and 70 (95% CI [63, 76]) kcal/kg/day, respectively, while REE in children with SW was higher, 79 kcal/kg/day (95% CI [74, 84], p  = 0.018), than NW. REE in these groups was stable over time. In children with EM, REE increased from admission to discharge (65 kcal/kg/day, 95% CI [56, 73]) to 79 (95% CI [72, 86], p  = 0.0014) and was stable hereafter. Predictive equations underestimated REE in 92% of participants at all time points. Recommended feeding targets during the acute phase of illness in severely malnourished children exceeded REE. Acutely ill malnourished children are at risk of being overfed when implementing current international guidelines.

Children with medically complicated severe acute malnutrition (SAM) have high risk of inpatient mortality. Diarrhea, carbohydrate malabsorption, and refeeding syndrome may contribute to early mortality and delayed recovery. We tested the hypothesis that a lactose-free, low-carbohydrate F75 milk would serve to limit these risks, thereby reducing the number of days in the stabilization phase. In a multicenter double-blind trial, hospitalized severely malnourished children were randomized to receive standard formula (F75) or isocaloric modified F75 (mF75) without lactose and with reduced carbohydrate. The primary endpoint was time to stabilization, as defined by the World Health Organization (WHO), with intention-to-treat analysis. Secondary outcomes included in-hospital mortality, diarrhea, and biochemical features of malabsorption and refeeding syndrome. The trial was registered at clinicaltrials.gov (NCT02246296). Four hundred eighteen and 425 severely malnourished children were randomized to F75 and mF75, respectively, with 516 (61%) enrolled in Kenya and 327 (39%) in Malawi. Children with a median age of 16 months were enrolled between 4 December 2014 and 24 December 2015. One hundred ninety-four (46%) children assigned to F75 and 188 (44%) to mF75 had diarrhea at admission. Median time to stabilization was 3 days (IQR 2-5 days), which was similar between randomized groups (0.23 [95% CI -0.13 to 0.60], P = 0.59). There was no evidence of effect modification by diarrhea at admission, age, edema, or HIV status. Thirty-six and 39 children died before stabilization in the F75 and in mF75 arm, respectively (P = 0.84). Cumulative days with diarrhea (P = 0.27), enteral (P = 0.42) or intravenous fluids (P = 0.19), other serious adverse events before stabilization, and serum and stool biochemistry at day 3 did not differ between groups. The main limitation was that the primary outcome of clinical stabilization was based on WHO guidelines, comprising clinical evidence of recovery from acute illness as well as metabolic stabilization evidenced by recovery of appetite. Empirically treating hospitalized severely malnourished children during the stabilization phase with lactose-free, reduced-carbohydrate milk formula did not improve clinical outcomes. The biochemical analyses suggest that the lactose-free formulae may still exceed a carbohydrate load threshold for intestinal absorption, which may limit their usefulness in the context of complicated SAM. ClinicalTrials.gov NCT02246296.