Stool frequency recording in severe acute malnutrition ('StoolSAM'); an agreement study comparing maternal recall versus direct observation using diapers.

BACKGROUND: Approximately 50% of the deaths of children under the age of 5 can be attributed to undernutrition, which also encompasses severe acute malnutrition (SAM). Diarrhoea is strongly associated with these deaths and is commonly diagnosed solely based on stool frequency and consistency obtained through maternal recall. This trial aims to determine whether this approach is equivalent to a 'directly observed method' in which a health care worker directly observed stool frequency using diapers in hospitalised children with complicated SAM. METHODS: This study was conducted at 'Moyo' Nutritional Rehabilitation Unit, Queen Elizabeth Central Hospital, Malawi. Participants were children aged 5-59 months admitted with SAM. We compared 2 days of stool frequency data obtained with next-day maternal-recall versus a 'gold standard' in which a health care worker observed stool frequency every 2 h using diapers. After study completion, guardians were asked their preferred method and their level of education. RESULTS: We found poor agreement between maternal recall and the 'gold standard' of directly observed diapers. The sensitivity to detect diarrhoea based on maternal recall was poor, with only 75 and 56% of diarrhoea cases identified on days 1 and 2, respectively. However, the specificity was higher with more than 80% of children correctly classified as not having diarrhoea. On day 1, the mean stool frequency difference between the two methods was -0.17 (SD; 1.68) with limits of agreement (of stool frequency) of -3.55 and 3.20 and, similarly on day 2, the mean difference was -0.2 (SD; 1.59) with limits of agreement of -3.38 and 2.98. These limits extend beyond the pre-specified 'acceptable' limits of agreement (±1.5 stool per day) and indicate that the 2 methods are non-equivalent. The higher the stool frequency, the more discrepant the two methods were. Most primary care givers strongly preferred using diapers. CONCLUSIONS: This study shows lack of agreement between the assessment of stool frequency in SAM patients using maternal recall and direct observation of diapers. When designing studies, one should consider using diapers to determining diarrhoea incidence/prevalence in SAM patients especially when accuracy is essential. TRIAL REGISTRATION NUMBER: ISRCTN11571116 (registered 29/11/2013)

A quantitative cross-sectional survey of psychosocial stimulation and counselling interventions at nutritional rehabilitation units in Southern Malawi

Background Inpatient treatment at nutritional rehabilitation units (NRUs) is needed for children who have severe acute malnutrition (SAM) and acute illness, loss of appetite, or severe oedema. World Health Organization guidelines state that nutritional counselling should be done with primary caregivers at NRUs. These recommendations also include psychosocial stimulation interventions to improve developmental outcomes in children with SAM. However, there is limited information about the delivery of these types of interventions for caregivers and children in NRU settings. The primary objective of this research was therefore to obtain data about NRU resources, activities, and protocols relevant to psychosocial stimulation and counselling interventions during inpatient treatment of children with SAM. Methods A cross-sectional survey was administered by interview at all 16 NRUs in seven districts in Southern Malawi. Participants were health workers, nurses, and nutritionists employed at the respective NRUs. Results The response rate was 100% across NRUs. Half of participants said that psychosocial stimulation interventions are conducted at their respective NRUs, yet none of the NRUs have protocols for delivery of these interventions. Furthermore, 7/16 (44%) NRUs have no resources for psychosocial stimulation including play materials. Thirteen of 16 (81%) participants said that they feel this type of intervention is very important and 3/16 (19%) participants said that this somewhat important for children with SAM. All NRUs provide counselling to caregivers about breastfeeding and nutrition; 15/16 (94%) also give counselling about water, sanitation and hygiene. Conclusions Ultimately, results from this survey highlighted that there is a need to invest in comprehensive interventions to improve developmental and nutritional outcomes in these vulnerable children requiring admission to NRUs

A protocol for a proof-of-concept randomized control trial testing increased protein quantity and quality in ready-to-use therapeutic food in improving linear growth among 6-23-month-old children with severe wasting in Malawi

Introduction: 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. Aim: 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. Methods: We designed a higher protein quantity and quality RUTF for a proof-of-concept (PoC) double-blind randomized controlled trial. Outcomes: The primary outcome is a change in insulin-like growth factor-1 (IGF-1), a hormone positively associated with linear growth after four weeks of treatment. Secondary outcomes include changes in ponderal and linear growth and in body composition from baseline to eight weeks later; plasma amino acid profile at four weeks; acceptability and safety. Implications: 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. Trial registration: The trial has been registered on clinicaltrial.gov (NCT05737472)

Hypoallergenic and anti-inflammatory feeds in children with complicated severe acute malnutrition: an open randomised controlled 3-arm intervention trial in Malawi

Intestinal pathology in children with complicated severe acute malnutrition (SAM) persists despite standard management. Given the similarity with intestinal pathology in non-IgE mediated gastrointestinal food allergy and Crohn’s disease, we tested whether therapeutic feeds effective in treating these conditions may benefit children with complicated SAM. After initial clinical stabilisation, 95 children aged 6–23 months admitted at Queen Elizabeth Central Hospital, Blantyre, Malawi between January 1 st and December 31 st , 2016 were allocated randomly to either standard feeds, an elemental feed or a polymeric feed for 14 days. Change in faecal calprotectin as a marker of intestinal inflammation and the primary outcome was similar in each arm: elemental vs. standard 4.1 μg/mg stool/day (95% CI, −29.9, 38.15; P = 0.81) and polymeric vs. standard 10 (−23.96, 43.91; P = 0.56). Biomarkers of intestinal and systemic inflammation and mucosal integrity were highly abnormal in most children at baseline and abnormal values persisted in all three arms. The enteropathy in complicated SAM did not respond to either standard feeds or alternative therapeutic feeds administered for up to 14 days. A better understanding of the pathogenesis of the gut pathology in complicated SAM is an urgent priority to inform the development of improved therapeutic interventions

A reduced-carbohydrate and lactose-free formulation for stabilization among hospitalized children with severe acute malnutrition: A double-blind, randomized controlled trial

BackgroundChildren 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.Methods and findingsIn 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. ConclusionsEmpirically 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

A Systematic Review on the Optimal Dose and Duration of Ready-to-Use Therapeutic Food (RUTF) for 6–59-Month-Old Children with Severe Wasting or Oedema

The World Health Organisation (WHO) recommends that severe wasting and/or oedema should be treated with ready-to-use therapeutic food (RUTF) at a dose of 150–220 kcal/kg/day for 6–8 weeks. Emerging evidence suggests that variations of RUTF dosing regimens from the WHO recommendation are not inferior. We aimed to assess the comparative efficacy and effectiveness of different RUTF doses and durations in comparison with the current WHO RUTF dose recommendation for treating severe wasting and/or oedema among 6–59-month-old children. A systematic literature search identified three studies for inclusion, and the outcomes of interest included anthropometric recovery, anthropometric measures and indices, non-response, time to recovery, readmission, sustained recovery, and mortality. The study was registered with PROSPERO, CRD 42021276757. Only three studies were eligible for analysis. There was an overall high risk of bias for two of the studies and some concerns for the third study. Overall, there were no differences between the reduced and standard RUTF dose groups in all outcomes of interest. Despite the finding of no differences between reduced and standard-dose RUTF, the studies are too few to conclusively declare that reduced RUTF dose was more efficacious than standard RUTF

Psychosocial stimulation interventions for children with severe acute malnutrition: a systematic review

Background The WHO Guidelines for the inpatient treatment of severely malnourished children include a recommendation to provide sensory stimulation or play therapy for children with severe acute malnutrition (SAM). This systematic review was performed to synthesize evidence around this recommendation. Specifically, the objective was to answer the question: "In children with severe acute malnutrition, does psychosocial stimulation improve child developmental, nutritional, or other outcomes?" Methods A review protocol was registered on the International Prospective Register of Systematic Reviews (PROSPERO 2016: CRD42016036403). MEDLINE, Embase, CINAHL, and PsycINFO were searched with terms related to SAM and psychosocial stimulation. Studies were selected if they applied a stimulation intervention in children with SAM and child developmental and nutritional outcomes were assessed. Findings were presented within a narrative synthesis and a summary of findings table. Quality of the evidence was evaluated using the Cochrane risk of bias tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Findings Only two studies, both non-randomized controlled trials, met the selection criteria for this review. One was conducted in Jamaica (1975) with a follow-up period of 14 years; the other was done in Bangladesh (2002) with a six-month follow-up. At the individual study level, each of the included studies demonstrated significant differences in child development outcomes between intervention and control groups. Only the study conducted in Bangladesh demonstrated a clinically significant increase in weight-for-age z-scores in the intervention group compared to the control group. Conclusions The evidence supporting the recommendation of psychosocial stimulation for children with SAM is not only sparse, but also of very low quality across important outcomes. High-quality trials are needed to determine the effects of psychosocial stimulation interventions on outcomes in children with SA

Intestinal pathogen clearance in children with severe acute malnutrition is unrelated to inpatient morbidity

Background & aims: Children with Severe Acute Malnutrition (SAM) often suffer from diarrhea, which is associated with increased mortality. The contribution of intestinal bacteria, parasites and viruses to morbidity such as diarrhea in SAM remains poorly understood. To evaluate their association with clinical outcomes, we detected stool pathogens in children with SAM at hospital admission and after clinical stabilization prior to discharge. Methods: 15 intestinal pathogens, fecal calprotectin and C-reactive protein (CRP) were determined at admission and after clinical stabilization in children aged 8-59 months (n = 47) hospitalized in Malawi for complicated SAM. Differences in fecal pathogens, intestinal and systemic inflammation, and clinical outcomes between time points were evaluated using the Wilcoxon Signed-Rank test or Wilcoxon rank-sum test. Results: On admission pathogens were present in nearly all children and after clinical stabilization many were cleared with only 55% of children still harboring a pathogen (89% vs. 55%, p = 0.001). Nosocomial infections were infrequent. The pathogens Giardia lamblia and Shigella spp. were most likely to persist. After clinical stabilization, fecal calprotectin was higher in children harboring a pathogen (median (IQR): 383 mg/kg (903-149 mg/kg) vs 140 mg/kg (300-71 mg/kg), p = 0.03). CRP did not correlate with fecal calprotectin levels nor was it associated with pathogen detection. Presence of stool pathogens was not associated with clinical outcomes such as diarrhea. Conclusions: Fecal pathogens were very common and cleared in most children with complicated SAM treated with antibiotics. The presence of stool pathogens after stabilization was associated with increased intestinal inflammation but not with clinical outcomes. (http://www.isrctn.com/ISRCTN13916953). (c) 2018 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved

Ready-to-Use Therapeutic Food (RUTF) Containing Low or No Dairy Compared to Standard RUTF for Children with Severe Acute Malnutrition : A Systematic Review and Meta-Analysis

Ready-to-use therapeutic food (RUTF) containing less dairy may be a lower-cost treatment option for severe acute malnutrition (SAM). The objective was to understand the effectiveness of RUTF containing alternative sources of protein (nondairy), or <50% of protein from dairy products, compared with standard RUTF in children with SAM. The Cochrane Library, MEDLINE, Embase, CINAHL, and Web of Science were searched using terms relating to RUTF. Studies were eligible if they included children with SAM and evaluated RUTF with <50% of protein from dairy products compared with standard RUTF. Meta-analysis and meta-regression were completed to assess the effectiveness of intervention RUTF on a range of child outcomes. The quality of the evidence across outcomes was assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. A total of 5868 studies were identified, of which 8 articles of 6 studies met the inclusion criteria evaluating 7 different intervention RUTF recipes. Nondairy or lower-dairy RUTF showed less weight gain (standardized mean difference:-0.20; 95% CI:-0.26,-0.15; P < 0.001), lower recovery (relative risk ratio: 0.93; 95% CI: 0.87, 1.00; P = 0.046), and lower weight-for-age z scores (WAZ) near program discharge (mean difference:-0.10; 95% CI:-0.20, 0.0; P = 0.047). Mortality, time to recovery, default (consecutive absences from outpatient therapeutic feeding program visits), nonresponse, and other anthropometric measures did not differ between groups. The certainty of evidence was high for weight gain and ranged from very low to moderate for other outcomes. RUTF with lower protein from dairy or dairy-free RUTF may not be as effective as standard RUTF for treatment of children with SAM based on weight gain, recovery, and WAZ evaluated using meta-analysis, although further research is required to explore the potential of alternative formulations. This review was registered at https://www.crd.york.ac.uk/prospero/as CRD42020160762.publishedVersionPeer reviewe

A quantitative cross-sectional survey of psychosocial stimulation and counselling interventions at nutritional rehabilitation units in southern Malawi

Background Inpatient treatment at nutritional rehabilitation units (NRUs) is needed for children who have severe acute malnutrition (SAM) and acute illness, loss of appetite, or severe oedema. World Health Organization guidelines state that nutritional counselling should be done with primary caregivers at NRUs. These recommendations also include psychosocial stimulation interventions to improve developmental outcomes in children with SAM. However, there is limited information about the delivery of these types of interventions for caregivers and children in NRU settings. The primary objective of this research was therefore to obtain data about NRU resources, activities, and protocols relevant to psychosocial stimulation and counselling interventions during inpatient treatment of children with SAM. Methods A cross-sectional survey was administered by interview at all 16 NRUs in seven districts in Southern Malawi. Participants were health workers, nurses, and nutritionists employed at the respective NRUs. Results The response rate was 100% across NRUs. Half of participants said that psychosocial stimulation interventions are conducted at their respective NRUs, yet none of the NRUs have protocols for delivery of these interventions. Furthermore, 7/16 (44%) NRUs have no resources for psychosocial stimulation including play materials. Thirteen of 16 (81%) participants said that they feel this type of intervention is very important and 3/16 (19%) participants said that this somewhat important for children with SAM. All NRUs provide counselling to caregivers about breastfeeding and nutrition; 15/16 (94%) also give counselling about water, sanitation and hygiene. Conclusions Ultimately, results from this survey highlighted that there is a need to invest in comprehensive interventions to improve developmental and nutritional outcomes in these vulnerable children requiring admission to NRUs