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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 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

Introduction: Many acutely ill children in low- and middle-income settings have a high risk of mortality both during and after hospitalisation despite guideline-based care. Understanding the biological mechanisms underpinning mortality may suggest optimal pathways to target for interventions to further reduce mortality. The Childhood Acute Illness and Nutrition (CHAIN) Network (www.chainnnetwork.org) Nested Case-Cohort Study (CNCC) aims to investigate biological mechanisms leading to inpatient and post-discharge mortality through an integrated multi-omic approach. Methods and analysis; The CNCC comprises a subset of participants from the CHAIN cohort (1278/3101 hospitalised participants, including 350 children who died and 658 survivors, and 270/1140 well community children of similar age and household location) from nine sites in six countries across sub-Saharan Africa and South Asia. Systemic proteome, metabolome, lipidome, lipopolysaccharides, haemoglobin variants, toxins, pathogens, intestinal microbiome and biomarkers of enteropathy will be determined. Computational systems biology analysis will include machine learning and multivariate predictive modelling with stacked generalization approaches accounting for the different characteristics of each biological modality. This systems approach is anticipated to yield mechanistic insights, show interactions and behaviours of the components of biological entities, and help develop interventions to reduce mortality among acutely ill children. Ethics and dissemination. The CHAIN Network cohort and CNCC was approved by institutional review boards of all partner sites. Results will be published in open access, peer reviewed scientific journals and presented to academic and policy stakeholders. Data will be made publicly available, including uploading to recognised omics databases. Trial registration NCT03208725.

Children admitted to hospital with an acute illness and concurrent severe malnutrition [complicated severe malnutrition (CSM)] have a high risk of dying. The biological processes underlying their mortality are poorly understood. In this case-control study nested within a multicenter randomized controlled trial among children with CSM in Kenya and Malawi, we found that blood metabolomic and proteomic profiles robustly differentiated children who died ( n = 92) from those who survived ( n = 92). Fatalities were characterized by increased energetic substrates (tricarboxylic acid cycle metabolites), microbial metabolites (e.g., propionate and isobutyrate), acute phase proteins (e.g., calprotectin and C-reactive protein), and inflammatory markers (e.g., interleukin-8 and tumor necrosis factor–α). These perturbations indicated disruptions in mitochondria-related bioenergetic pathways and sepsis-like responses. This study identified specific biomolecular disturbances associated with CSM mortality, revealing that systemic inflammation and bioenergetic deficits are targetable pathophysiological processes for improving survival of this vulnerable population.

Minimally invasive tissue sampling (MITS) is increasingly being used to better understand causes of death in low-resource settings. Undernutrition (eg, wasting, stunting) is prevalent among children globally and yet not consistently coded or uniformly included on death certificates in MITS studies when present. Consistent and accurate attribution of undernutrition is fundamental to understanding its contribution to child deaths. In May 2020, members of the MITS Alliance Cause of Death Technical Working Group convened a panel of experts in public health, child health, nutrition, infectious diseases, and MITS to develop guidance for systematic integration of undernutrition, as assessed by anthropometry, in cause of death coding, including as part of the causal chain or as a contributing condition, in children

Background There is significant need for accurate diagnostic tools for Cryptosporidium spp. and Giardia duodenalis infections in resource limited countries where diarrhoeal disease caused by these parasites is often prevalent. The present study assessed the diagnostic performance of three commercially available rapid diagnostic tests (RDTs) based on faecal-antigen detection for Cryptosporidium spp. and/or G. duodenalis infections in stool samples of children admitted with severe acute malnutrition (SAM) and diarrhoea. An established multiplex PCR was used as reference test. Methods Stool samples from children with SAM and diarrhoea enrolled in a randomized controlled trial (registered at clinicaltrials.gov/ct2/show/NCT02246296) in Malawi (n = 175) and Kenya (n = 120) between December 2014 and December 2015 were analysed by a multiplex PCR for the presence of Cryptosporidium spp., G. duodenalis or Entamoeba histolytica parasite DNA. Cryptosporidium-positive samples were species typed using restriction fragment length polymorphism analysis. A sub-sample of the stool specimens (n = 236) was used for testing with three different RDTs. Diagnostic accuracy of the tests under evaluation was assessed using the results of PCR as reference standard using MedCalc software. Pearson Chi-square test and Fisher’s exact test were used to determine (significant) difference between the number of cryptosporidiosis or giardiasis cases found by PCR in Malawi and Kenya. The overall diagnostic accuracy of each RDT was calculated by plotting a receiver operating characteristic (ROC) curve for each test and to determine the area under the curve (AUC) using SPSS8 software. Results Prevalence of Cryptosporidium spp. by PCR was 20.0 and 21.7% in Malawi and Kenya respectively, mostly C. hominis. G. duodenalis prevalence was 23.4 and 5.8% in Malawi and Kenya respectively. E. histolytica was not detected by PCR. RDT testing followed the same pattern of prevalence. RDT sensitivities ranged for cryptosporidiosis from 42.9 to 76.9% and for G. duodenalis from 48.2 to 85.7%. RDT specificities ranged from 88.4 to 100% for Cryptosporidium spp. and from 91.2 to 99.2% for G. duodenalis infections. Based on the estimated area under the curve (AUC) values, all tests under evaluation had an acceptable overall diagnostic accuracy (> 0.7), with the exception of one RDT for Cryptosporidium spp. in Malawi. Conclusions All three RDTs for Cryptosporidium spp. and Giardia duodenalis evaluated in this study have a moderate sensitivity, but sufficient specificity. The main value of the RDTs is within their rapidness and their usefulness as screening assays in surveys for diarrhoea.

BackgroundChild mortality rates remain unacceptably high in low-resource settings. Cause of death (CoD) is often unknown. Minimally invasive tissue sampling (MITS)–using biopsy needles to obtain post-mortem samples–for histopathological and microbiologic investigation is increasingly being promoted to improve child and adult CoD attribution. “MITS in Malawi” is a sub-study of the Childhood Acute Illness & Nutrition (CHAIN) Network, which aims to identify biological and socioeconomic mortality risk factors among young children hospitalized for acute illness or undernutrition. MITS in Malawi employs standard MITS and a novel post-mortem endoscopic intestinal sampling approach to better understand CoD among children with acute illness and/or malnutrition who die during hospitalization.AimTo understand factors that may impact MITS acceptability and inform introduction of the procedure to ascertain CoD among children with acute illness or malnutrition who die during hospitalization in Malawi.MethodsWe conducted eight focus group discussions with key hospital staff and community members (religious leaders and parents of children under 5) to explore attitudes towards MITS and inform consent processes prior to commencing the MITS in Malawi study. We used thematic content analysis drawing on a conceptual framework developed from emergent themes and MITS acceptability literature.ResultsFeelings of power over decision-making within the hospital and household, trust in health systems, and open and respectful health worker communication with parents were important dimensions of MITS acceptability. Other facilitating factors included the potential for MITS to add CoD information to aid sense-making of death and contribute to medical knowledge and new interventions. Potential barriers to acceptability included fears of organ and blood harvesting, disfigurement to the body, and disruption to transportation and burial plans.ConclusionSocial relationships and power dynamics within healthcare systems and households are a critical component of MITS acceptability, especially given the sensitivity of death and autopsy.

Background Intestinal disorders such as environmental enteric dysfunction (EED) are prevalent in low- and middle-income countries (LMICs) and important contributors to childhood undernutrition and mortality. Autopsies are rarely performed in LMICs but minimally invasive tissue sampling is increasingly deployed as a more feasible and acceptable procedure, although protocols have been devoid of intestinal sampling to date. We sought to determine (1) the feasibility of postmortem intestinal sampling, (2) whether autolysis precludes enteric biopsies’ utility, and (3) histopathologic features among children who died during hospitalization with acute illness or undernutrition. Methods Transabdominal needle and endoscopic forceps upper and lower intestinal sampling were conducted among children aged 1 week to 59 months who died while hospitalized in Blantyre, Malawi. Autolysis ratings were determined for each hematoxylin and eosin slide, and upper and lower intestinal scoring systems were adapted to assess histopathologic features and their severity. Results Endoscopic and transabdominal sampling procedures were attempted in 28 and 14 cases, respectively, with >90% success obtaining targeted tissue. Varying degrees of autolysis were present in all samples and precluded histopathologic scoring of 6% of 122 biopsies. Greater autolysis in duodenal samples was seen with longer postmortem interval (Beta = 0.06, 95% confidence interval, 0.02–0.11). Histopathologic features identified included duodenal Paneth and goblet cell depletion. Acute inflammation was absent but chronic inflammation was prevalent in both upper and lower enteric samples. Severe chronic rectal inflammation was identified in children as young as 5.5 weeks. Conclusions Minimally invasive postmortem intestinal sampling is feasible and identifies histopathology that can inform mortality contributors.

Children with severe acute malnutrition (SAM) display immature, altered gut microbiota and have a high mortality risk. Faecal volatile organic compounds (VOCs) reflect the microbiota composition and may provide insight into metabolic dysfunction that occurs in SAM. Here we determine whether analysis of faecal VOCs could identify children with SAM with increased risk of mortality. VOC profiles from children who died within six days following admission were compared to those who were discharged alive using machine learning algorithms. VOC profiles of children who died could be separated from those who were discharged with fair accuracy (AUC) = 0.71; 95% CI 0.59–0.87; P = 0.004). We present the first study showing differences in faecal VOC profiles between children with SAM who survived and those who died. VOC analysis holds potential to help discover metabolic pathways within the intestinal microbiome with causal association with mortality and target treatments in children with SAM.Trial Registration: The F75 study is registered at clinicaltrials.gov/ct2/show/NCT02246296.

Background Children admitted to nutritional rehabilitation units (NRUs) for inpatient treatment of severe acute malnutrition (SAM) are at high risk of poor developmental and nutritional outcomes. The Kusamala Program is an interactive hospital-based counseling program for primary caregivers of children with SAM that integrates three modules: nutrition and feeding; water, sanitation, and hygiene (WASH); and psychosocial stimulation. This mixed methods feasibility study aimed to evaluate the implementation of the Kusamala Program in an NRU setting and developmental outcomes in children with SAM 6 months after inpatient treatment. Methods An internal pilot trial including the first 30 children and their primary caregivers enrolled to a cluster-randomized controlled trial of the Kusamala Program was performed. Barriers and enablers were identified in a qualitative study with a focus group discussion (FGD) and in-depth interviews (IDIs) with 12 hospital staff members, including five NRU nurses who deliver the Kusamala Program. Results Results demonstrated high participant engagement (100%) and adherence (87%) of primary caregivers to the Kusamala Program. Potential barriers to implementation identified through the qualitative study were caregivers’ perceived value of the program, prioritization of other ward activities, and shortages of staff. On the other hand, enablers to implementation were engaging other staff members, motivation and work ethic, and refresher training. Conclusions This mixed methods study demonstrates the feasibility of implementing the Kusamala Program in a real NRU setting. The full cluster-randomized controlled trial will be completed to evaluate the effectiveness of the Kusamala Program. Trial registration ClinicalTrials.gov, NCT03072433. Registered on 7 March 2017—retrospectively registered

Background:Despite a reduction of child mortality in low-income countries, acutely ill undernourished children still have an elevated risk of death. Those at highest risk are children with severe acute malnutrition (SAM) who often show metabolic dysregulation that remains poorly understood.Objective:We performed a pilot study to examine changes in urinary organic acids during nutritional rehabilitation of children with SAM, and to identify metabolites associated with the presence of edema or with mortality.Methods:This study included 76 children aged between 6 and 60 months, hospitalized for SAM at the Moyo Nutritional Rehabilitation and Research Unit in Blantyre, Malawi. Urine was collected at admission and 3 days after clinical stabilization and metabolomics were performed using gas chromatography–mass spectrometry. Metabolite concentrations were evaluated with both uni- and multivariate approaches.Results:Most metabolites increased 3 days after clinical stabilization, and total urinary concentration changed from 1.2 mM (interquartile range [IQR], 0.78-1.7) at admission to 3.8 mM (IQR, 2.1-6.6) after stabilization ( P < .0001). In particular, 6 metabolites showed increases: 3-hydroxybutyric, 4-hydroxyhippuric, p-hydroxyphenylacetic, oxoglutaric, succinic, and lactic acids. Urinary creatinine was low at both time points, but levels did increase from 0.63 mM (IQR, 0.2-1.2) to 2.6 mM (IQR,1.6-4.4; P < .0001). No differences in urinary profiles were found between children who died versus those who survived, nor between children with severe wasting or edematous SAM.Conclusions:Total urinary metabolites and creatinine increase after stabilization and may reflect partial recovery of overall metabolism linked to refeeding. The use of urinary metabolites for risk assessment should be furthered explored.Trial registration:TranSAM study (ISRCTN13916953).

BackgroundInpatient 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. MethodsA 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. ResultsThe 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. ConclusionsUltimately, 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.

Objective The relation between malnutrition and exocrine pancreatic insufficiency (EPI) has been described previously, but it is unclear if malnutrition leads to EPI or vice versa. We systematically synthesized current evidence evaluating the association between malnutrition and EPI in children. Methods Pubmed, Embase, and Cochrane databases were searched from inception until February 2017. We included cohort or case-controlled studies in children reporting on prevalence or incidence of EPI and malnutrition. Data generation was performed independently by 2 authors. Quality was assessed by using quality assessment tools from the National Heart, Lung, and Blood Institute. Results Nineteen studies were divided into 2 groups: 10 studies showing EPI leading to malnutrition, and 9 studies showing malnutrition leading to EPI. Because of heterogeneity in design, definitions, and outcome measures, pooling of results was impossible. Quality was good in 4 of 19 studies. Pancreatic insufficiency was linked to decreased nutritional status in 8 of 10 articles, although this link was not specified properly in most articles. In malnourished children, improvement was seen in pancreatic function in 7 of 9 articles after nutritional rehabilitation. The link between the 2 was not further specified. Heterogeneity exists with respect to definitions, outcome measures, and study design. Conclusions There is sufficient evidence for an association between EPI and malnutrition. We could not confirm whether there is a correlation or causality between EPI or malnutrition. It was therefore not possible to draw firm conclusions from this systematic review on underlying pathophysiological mechanisms between EPI and malnutrition. More observational clinical trials are crucially needed.

Children with severe acute malnutrition (SAM) display immature, altered gut microbiota and have a high mortality risk. Faecal volatile organic compounds (VOCs) reflect the microbiota composition and may provide insight into metabolic dysfunction that occurs in SAM. Here we determine whether analysis of faecal VOCs could identify children with SAM with increased risk of mortality. VOC profiles from children who died within six days following admission were compared to those who were discharged alive using machine learning algorithms. VOC profiles of children who died could be separated from those who were discharged with fair accuracy (AUC) = 0.71; 95% CI 0.59-0.87; P = 0.004). We present the first study showing differences in faecal VOC profiles between children with SAM who survived and those who died. VOC analysis holds potential to help discover metabolic pathways within the intestinal microbiome with causal association with mortality and target treatments in children with SAM.Trial Registration: The F75 study is registered at clinicaltrials.gov/ct2/show/NCT02246296.

Background Severe acute malnutrition (SAM) affects approximately 18 million children under the age of five and is associated with more than 500 thousand deaths per year. Existing research has indicated that a high number of caregivers of children admitted for inpatient treatment of SAM experience psychological distress, depressive symptoms, and suicidality. However, no published studies in Malawi have been undertaken to qualitatively explore caregivers’ perceptions and experiences regarding their children’s malnutrition and inpatient treatment. Aim To explore caregivers’ perceptions and experiences surrounding childhood acute malnutrition and the experience of inpatient care in Malawi. Methods Interviews were conducted utilising a semi-structured topic guide and were coded using thematic analysis. Results Caregivers (N=30) gave informed consent to participate in interviews. Caregiver understanding and perceptions of their children’s illness varied. Some caregivers identified a physical cause, with a minority identifying lack of dietary protein. Other narratives were around characteristics of the infant, other circumstantial events and religious and spiritual influences. One-third of caregivers described their own health difficulties and marital and relationship stressors. Challenges such as poverty, lack of access to food, poor food variability and competing demands for caregiver time were explained. Both positive and negative experiences of family and community support and hospital-based care were reported. Conclusion The themes identified contribute to a greater contextual understanding of the multifactorial and integrated approaches required to address malnutrition. This study indicates that healthcare providers need to take a multi-faceted view of malnutrition and be aware of the many factors that may influence healthcare experience and response to treatment. Acknowledging pluralistic belief systems may improve engagement with care. This demands a broader appreciation of perceptions and experiences of malnutrition, hospital-based care, sources of support and stressors within the caregiver, family and community environment as well as consideration of social determinants such as poverty and how these influences present within a clinical context.

Background Due to a lack of systematic diagnostics, our understanding of the diversity and role of eukaryotic microbiota in human health is limited. While studies have shown fungal communities to be significant modulators of human health, information on the prevalence of taxa such as protozoa and helminths has been limited to a small number of species for which targeted molecular diagnostics are available. To probe the diversity of eukaryotic microbes and their relationships with other members of the microbiota, we applied in silico and experimental approaches to design a novel two-amplicon surveillance tool, based on sequencing regions of ribosomal RNA genes and their internal transcribed spacers. We subsequently demonstrated the utility of our approach by characterizing the eukaryotic microbiota of 46 hospitalized Malawian children suffering from Severe Acute Malnutrition (SAM). Results Through in silico analysis and validation on a diverse panel of eukaryotes, we identified 18S rRNA variable genetic regions 4 and 5 (18S V4 V5), together with a region encoding 28S rRNA variable genetic region 2 and the internal transcribed spacers (transITS), as optimal for the systematic classification of eukaryotes. Sequencing of these regions revealed protozoa in all stool samples from children with SAM and helminths in most, including several eukaryotes previously implicated in malnutrition and diarrheal disease. Clinical comparisons revealed no association between protozoan parasites and diarrhea or HIV reactivity. However, the presence of Blastocystis correlated with bacterial alpha diversity and increased abundance of specific taxa, including Sporobacter, Cellulosibacter, Oscillibacter, and Roseburia. Conclusion We suggest this novel two-amplicon based strategy will prove an effective tool to deliver new insights into the role of eukaryotic microbiota in health and disease. Electronic supplementary material The online version of this article (10.1186/s40168-018-0612-3) contains supplementary material, which is available to authorized users.

BACKGROUND: Early childhood development provides an important foundation for the development of human capital. Although there is a clear relation between stunting and child development outcomes, less information is available about the developmental and behavioural outcomes of children with severe acute malnutrition (SAM). Particularly an important research gap exists in Sub-Saharan Africa where there is a high prevalence of SAM and a high rate of co-occurring HIV (human immune deficiency virus) infection. Our first objective was to assess the prevalence and severity of developmental and behavioural disorders on a cohort of children admitted to an inpatient nutritional rehabilitation centre in Malawi. Our second objective was to compare the developmental and behavioural profiles of children with the two main phenotypes of SAM: kwashiorkor and marasmus. METHODS: This was a cross-sectional observational study including all children hospitalized with complicated SAM in Blantyre, Malawi over an 8-month period from February to October 2015. At discharge, children were assessed with the well-validated Malawi Developmental Assessment Tool (MDAT) for gross motor, fine motor, language and social development. In children ≥24 months, emotional and behavioural problems were measured using the Strengths and Difficulties Questionnaire (SDQ). RESULTS: 150 children (55% boys) with SAM were recruited; mean age of 27.2 months (standard deviation 17.9), 27 children (18%) had pre-existing neurodisabilities (ND) and 34 (23%) had a co-occurring human immune deficiency virus (HIV) infection. All children with SAM experienced profound delays in the gross and fine motor, language and social domains. Linear regression analysis demonstrated that children with kwashiorkor scored 0.75 standard deviations lower (95% confidence interval -1.43 to -0.07) on language MDAT domain than children with marasmus when adjusted for covariates. The prosocial behaviour score of the SDQ was low in children with SAM, indicating a lack of sensitive behaviour in social interactions. CONCLUSIONS: Children with SAM have severe developmental delays after a hospital admission. Our results indicate that there might be a significant difference in developmental attainment between children with kwashiorkor and with marasmus. Future studies exploring longer-term outcomes and testing possible intervention strategies are urgently needed.

Objective: To assess the benefits of pancreatic enzyme replacement therapy (PERT) in children with complicated severe acute malnutrition.Study design: We conducted a randomized, controlled trial in 90 children aged 6-60 months with complicated severe acute malnutrition at the Queen Elizabeth Central Hospital in Malawi. All children received standard care; the intervention group also received PERT for 28 days.Results: Children treated with PERT for 28 days did not gain more weight than controls (13.7 +/- 9.0% in controls vs 15.3 +/- 11.3% in PERT; P = .56). Exocrine pancreatic insufficiency was present in 83.1% of patients on admission and fecal elastase-1 levels increased during hospitalization mostly seen in children with nonedematous severe acute malnutrition (P Conclusions: PERT does not improve weight gain in severely malnourished children but does increase the rate of hospital discharge. Mortality was lower in patients on PERT, a finding that needs to be investigated in a larger cohort with stratification for edematous and nonedematous malnutrition. Mortality in severe acute malnutrition is associated with markers of poor digestive function.

The case fatality rate of severely malnourished children during inpatient treatment is high and mortality is often associated with diarrhea. As intestinal carbohydrate absorption is impaired in severe acute malnutrition (SAM), differences in dietary formulations during nutritional rehabilitation could lead to the development of osmotic diarrhea and subsequently hypovolemia and death. We compared three dietary strategies commonly used during the transition of severely malnourished children to higher caloric feeds, i.e., F100 milk (F100), Ready-to-Use Therapeutic Food (RUTF) and RUTF supplemented with F75 milk (RUTF + F75). In this open-label pilot randomized controlled trial, 74 Malawian children with SAM aged 6–60 months, were assigned to either F100, RUTF or RUTF + F75. Our primary endpoint was the presence of low fecal pH (pH ≤ 5.5) measured in stool collected 3 days after the transition phase diets were introduced. Secondary outcomes were duration of hospital stay, diarrhea and other clinical outcomes. Chi-square test, two-way analysis of variance and logistic regression were conducted and, when appropriate, age, sex and initial weight for height Z-scores were included as covariates. The proportion of children with acidic stool (pH ≤5.5) did not significantly differ between groups before discharge with 30, 33 and 23% for F100, RUTF and RUTF + F75, respectively. Mean duration of stay after transitioning was 7.0 days (SD 3.4) with no differences between the three feeding strategies. Diarrhea was present upon admission in 33% of patients and was significantly higher (48%) during the transition phase (p

ObjectiveSevere acute malnutrition (SAM) is a major cause of mortality in children under 5 years and is associated with hepatic steatosis. Bile acids are synthesized in the liver and participate in dietary fat digestion, regulation of energy expenditure, and immune responses. The aim of this work was to investigate whether SAM is associated with clinically relevant changes in bile acid homeostasis.DesignAn initial discovery cohort with 5 healthy controls and 22 SAM-patients was used to identify altered bile acid homeostasis. A follow up cohort of 40 SAM-patients were then studied on admission and 3 days after clinical stabilization to assess recovery in bile acid metabolism. Recruited children were 6-60 months old and admitted for SAM in Malawi. Clinical characteristics, feces and blood were collected on admission and prior to discharge. Bile acids, 7ahydroxy-4-cholesten-3-one (C4) and FGF-19 were quantified.ResultsOn admission, total serum bile acids were higher in children with SAM than in healthy controls and glycine-conjugates accounted for most of this accumulation with median and interquartile range (IQR) of 24.6 mu mol/L [8.6-47.7] compared to 1.9 mu mol/L [1.7-3.3] (p = 0.01) in controls. Total serum bile acid concentrations did not decrease prior to discharge. On admission, fecal conjugated bile acids were lower and secondary bile acids higher at admission compared to pre-discharge, suggesting increased bacterial conversion. FGF19 (Fibroblast growth factor 19), a marker of intestinal bile acid signaling, was higher on admission and was associated with decreased C4 concentrations as a marker of bile acid synthesis. Upon recovery, fecal calprotectin, a marker of intestinal inflammation, was lower.ConclusionSAM is associated with increased serum bile acid levels despite reduced synthesis rates. In SAM, there tends to be increased deconjugation of bile acids and conversion from primary to secondary bile acids, which may contribute to the development of liver disease.

Context: Severe acute malnutrition (SAM) accounts for approximately 1 million child deaths per year. High mortality is linked with comorbidities, such as diarrhea and pneumonia. Objective: The aim of this systematic review was to determine the extent to which carbohydrate malabsorption occurs in children with SAM. Data Sources: The PubMed and Embase databases were searched. Reference lists of selected articles were checked. Data Extraction: All observational and controlled intervention studies involving children with SAM in which direct or indirect measures of carbohydrate absorption were analyzed were eligible for inclusion. A total of 20 articles were selected for this review. Data Synthesis: Most studies reported carbohydrate malabsorption, particularly lactose malabsorption, and suggested an increase in diarrhea and reduced weight gain in children on a lactose-containing diet. As most studies reviewed were observational, there was no conclusive scientific evidence of a causal relationship between lactose malabsorption and a worse clinical outcome among malnourished children. Conclusion: The combined data indicate that carbohydrate malabsorption is prevalent in children with SAM. Additional well-designed intervention studies are needed to determine whether outcomes of SAM complicated by carbohydrate malabsorption could be improved by altering the carbohydrate/lactose content of therapeutic feeds and to elucidate the precise mechanisms involved.

BACKGROUND: The data concerning the value of a plain abdominal radiograph in childhood constipation are inconsistent. Recently, positive results have been reported of a new radiographic scoring system, "the Leech method", for assessing faecal loading. OBJECTIVE: To assess intra- and interobserver variability and determine diagnostic accuracy of the Leech method in identifying children with functional constipation (FC). MATERIALS AND METHODS: A total of 89 children (median age 9.8 years) with functional gastrointestinal disorders were included in the study. Based on clinical parameters, 52 fulfilled the criteria for FC, six fulfilled the criteria for functional abdominal pain (FAP), and 31 for functional non-retentive faecal incontinence (FNRFI); the latter two groups provided the controls. To assess intra- and interobserver variability of the Leech method three scorers scored the same abdominal radiograph twice. A Leech score of 9 or more was considered as suggestive of constipation. ROC analysis was used to determine the diagnostic accuracy of the Leech method in separating patients with FC from control patients. RESULTS: Significant intraobserver variability was found between two scorers (P=0.005 and P

Background: There is an inverse relationship between gestational age, birth weight and the time of first neonatal bowel movement. The authors hypothesized that delayed passage of meconium might result from a delayed maturation of the rectoanal inhibitory reflex (RAIR) in premature infants. Objective: To evaluate whether the RAIR is absent in very preterm infants 28-32 weeks postmenstrual age with delayed meconium production. Study design: Anorectal manometry was performed in 10 preterm infants (seven male) with delayed meconium production (no meconium in the first 48 hours). Median postmenstrual age was 30 weeks (28-31 weeks). Birth weight ranged from 780 to 1930 g (median, 1395 g). A micromanometric assembly (outer diameter, 2.0 mm) was used which incorporated a 1.5-cm-long sleeve sensor for measurement of resting anal sphincter pressure and relaxation. Four side-holes recorded anal and rectal pressures. Rectal distension was performed with direct air insufflation to elicit the RAIR. Results: The time from birth to passage of meconium ranged from 48 to 105 hours (median, 82 hours). The mean anal sphincter pressure, rectal pressure, and anal sphincter oscillation frequency were 22.0 +/- 5.0 mm Hg, 6.9 +/- 2.0 mm Hg, and 9.8 +/- 1.9/min, respectively. A normal RAIR was elicited in all infants. Conclusion: Anorectal manometry recordings in premature infants with delayed passage of meconium showed normal anorectal pressures and a normal RAIR, suggesting that delayed meconium passage is not related to the absence of a RAIR. (c) 2005 Lippincott Williarns C Wilkins

Malnutrition and neurodisability are both major public health problems in Africa. This review highlights key areas where they interact. This happens throughout life and starts with maternal malnutrition affecting fetal neurodevelopment with both immediate (eg, folate deficiency causing neural tube defects) and lifelong implications (eg, impaired cognitive function). Maternal malnutrition can also increase the risk of perinatal problems, including birth asphyxia, a major cause of neurologic damage and cerebral palsy. Macronutrient malnutrition can both cause and be caused by neurodisability. Mechanisms include decreased food intake, increased nutrient losses, and increased nutrient requirement. Specific micronutrient deficiencies can also lead to neurodisability, for example, blindness (vitamin A), intractable epilepsy (vitamin B6), and cognitive impairment (iodine and iron). Toxin ingestion (eg, from poorly processed cassava) can cause neurodisability including a peripheral polyneuropathy and a spastic paraparesis. We conclude that there is an urgent need for nutrition and disability programs to work more closely together.

BACKGROUND & AIMS: Increased rectal compliance has been proposed to contribute to pediatric functional constipation (FC). We evaluated the clinical relevance of increased rectal compliance and assessed whether regular use of enemas improves rectal compliance in children with FC. METHODS: A prospective longitudinal study was conducted on children (8-18 years old) with FC. Pressure-controlled rectal distensions were performed at baseline and at 1 year. Rectal compliance was categorized into 3 groups: normal, moderately increased, or severely increased. Patients were randomly assigned to groups given conventional therapy or rectal enemas and conventional therapy. Clinical success was defined as >or=3 spontaneous defecations per week and fecal incontinence

Functional gastrointestinal disorder is a common problem in childhood. The symptoms vary from a relative mild gastrointestinal problem such as abdominal pain or infrequent defecation to severe problems with fecal impaction and fecal incontinence. The aim of this review is to describe and evaluate the value of the different existing methods to assess fecal loading on an abdominal radiograph with or without the use of radio-opaque markers in the diagnosis of functional abdominal pain, functional constipation and functional non-retentive fecal incontinence. In our opinion, the abdominal radiograph has limited value in the diagnostic work-up of children with functional gastrointestinal disorders.

BACKGROUND & AIMS: Functional nonretentive fecal incontinence (FNRFI), incontinence in the absence of signs of fecal retention, is a frustrating phenomenon in children. No data on long-term outcome are available. The aim was to investigate the long-term outcome of FNRFI patients after intensive medical treatment. METHODS: Between 1990 and 1999, 119 patients (96 boys) with FNRFI were enrolled in 2 prospective, randomized trials investigating the effect of biofeedback training and/or laxative treatment. Follow-up (FU) was performed at 6 months, 1 year, and thereafter annually until September 2004. A standardized questionnaire was used to evaluate symptoms. Success was defined as a fecal incontinence frequency