Highly prevalent conditions with multiple and complex underlying etiologies are a challenge to public health. Undernutrition, for example, affects 20% of children in the developing world. The cause ...and consequence of poor nutrition are multifaceted. Undernutrition has been associated with half of all deaths worldwide in children aged <5 years; in addition, its pernicious long-term effects in early childhood have been associated with cognitive and physical growth deficits across multiple generations and have been thought to suppress immunity to further infections and to reduce the efficacy of childhood vaccines. The Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health (MAL-ED) Study, led by the Fogarty International Center of the National Institutes of Health and the Foundation for the National Institutes of Health, has been established at sites in 8 countries with historically high incidence of diarrheal disease and undernutrition. Central to the study is the hypothesis that enteropathogen infection contributes to undernutrition by causing intestinal inflammation and/or by altering intestinal barrier and absorptive function. It is further postulated that this leads to growth faltering and deficits in cognitive development. The effects of repeated enteric infection and undernutrition on the immune response to childhood vaccines is also being examined in the study. MAL-ED uses a prospective longitudinal design that offers a unique opportunity to directly address a complex system of exposures and health outcomes in the community—rather than the relatively rarer circumstances that lead to hospitalization—during the critical period of development of the first 2 years of life. Among the factors being evaluated are enteric infections (with or without diarrhea) and other illness indicators, micronutrient levels, diet, socioeconomic status, gut function, and the environment. MAL-ED aims to describe these factors, their interrelationships, and their overall impact on health outcomes in unprecedented detail, and to make individual, site-specific, and generalized recommendations regarding the nature and timing of possible interventions aimed at improving child health and development in these resource-poor settings.
To examine the contributions of impaired gut microbial community development to childhood undernutrition, we combined metabolomic and proteomic analyses of plasma samples with metagenomic analyses of ...fecal samples to characterize the biological state of Bangladeshi children with severe acute malnutrition (SAM) as they transitioned, after standard treatment, to moderate acute malnutrition (MAM) with persistent microbiota immaturity. Host and microbial effects of microbiota-directed complementary food (MDCF) prototypes targeting weaning-phase bacterial taxa underrepresented in SAM and MAM microbiota were characterized in gnotobiotic mice and gnotobiotic piglets colonized with age- and growth-discriminatory bacteria. A randomized, double-blind controlled feeding study identified a lead MDCF that changes the abundances of targeted bacteria and increases plasma biomarkers and mediators of growth, bone formation, neurodevelopment, and immune function in children with MAM.
Objective:
Malnutrition is a major cause of childhood morbidity and mortality. To identify and target those at highest risk, there is a critical need to characterize biomarkers that predict ...complications prior to and during treatment.
Methods:
We used targeted and nontargeted metabolomic analysis to characterize changes in a broad array of hormones, cytokines, growth factors, and metabolites during treatment of severe childhood malnutrition. Children aged 6 months to 5 years were studied at presentation to Mulago Hospital and during inpatient therapy with milk-based formulas and outpatient supplementation with ready-to-use food. We assessed the relationship between baseline hormone and metabolite levels and subsequent mortality.
Results:
Seventy-seven patients were enrolled in the study; a subset was followed up from inpatient treatment to the outpatient clinic. Inpatient and outpatient therapies increased weight/height z scores and induced striking changes in the levels of fatty acids, amino acids, acylcarnitines, inflammatory cytokines, and various hormones including leptin, insulin, GH, ghrelin, cortisol, IGF-I, glucagon-like peptide-1, and peptide YY. A total of 12.2% of the patients died during hospitalization; the major biochemical factor predicting mortality was a low level of leptin (P = .0002), a marker of adipose tissue reserve and a critical modulator of immune function.
Conclusions:
We have used metabolomic analysis to provide a comprehensive hormonal and metabolic profile of severely malnourished children at presentation and during nutritional rehabilitation. Our findings suggest that fatty acid metabolism plays a central role in the adaptation to acute malnutrition and that low levels of the adipose tissue hormone leptin associate with, and may predict, mortality prior to and during treatment.
...investments are needed to improve maternal and child nutrition through pregnancy, infancy, and early childhood by protecting breastfeeding and preventing the inappropriate marketing of infant ...formula in the context of COVID-19;6 securing children and women's access to nutritious and diverse foods; and providing accurate information on infant feeding to caregivers. ...services for the early detection and treatment of child wasting need to be re-activated and scaled up while maintaining and expanding prevention and other nutrition services, including vitamin A supplementation for children, and micronutrient supplementation and nutritional support for pregnant and breastfeeding women, and minimising the risk of infection. ...social protection to safeguard access to nutritious diets and essential services among the poorest households, including access to fortified foods, needs to be expanded.
Housing is essential to human well-being but neglected in global health. Today, housing in Africa is rapidly improving alongside economic development, creating an urgent need to understand how these ...changes can benefit health. We hypothesised that improved housing is associated with better health in children living in sub-Saharan Africa (SSA). We conducted a cross-sectional analysis of housing conditions relative to a range of child health outcomes in SSA.
Cross-sectional data were analysed for 824,694 children surveyed in 54 Demographic and Health Surveys, 21 Malaria Indicator Surveys, and two AIDS Indicator Surveys conducted in 33 countries between 2001 and 2017 that measured malaria infection by microscopy or rapid diagnostic test (RDT), diarrhoea, acute respiratory infections (ARIs), stunting, wasting, underweight, or anaemia in children aged 0-5 years. The mean age of children was 2.5 years, and 49.7% were female. Housing was categorised into a binary variable based on a United Nations definition comparing improved housing (with improved drinking water, improved sanitation, sufficient living area, and finished building materials) versus unimproved housing (all other houses). Associations between house type and child health outcomes were determined using conditional logistic regression within surveys, adjusting for prespecified covariables including age, sex, household wealth, insecticide-treated bed net use, and vaccination status. Individual survey odds ratios (ORs) were pooled using random-effects meta-analysis. Across surveys, improved housing was associated with 8%-18% lower odds of all outcomes except ARI (malaria infection by microscopy: adjusted OR aOR 0.88, 95% confidence intervals CIs 0.80-0.97, p = 0.01; malaria infection by RDT: aOR 0.82, 95% CI 0.77-0.88, p < 0.001; diarrhoea: aOR 0.92, 95% CI 0.88-0.97, p = 0.001; ARI: aOR 0.96, 95% CI 0.87-1.07, p = 0.49; stunting: aOR 0.83, 95% CI 0.77-0.88, p < 0.001; wasting: aOR 0.90, 95% CI 0.83-0.99, p = 0.03; underweight: aOR 0.85, 95% CI 0.80-0.90, p < 0.001; any anaemia: aOR 0.87, 95% CI 0.82-0.92, p < 0.001; severe anaemia: aOR 0.89, 95% CI 0.84-0.95, p < 0.001). In comparison, insecticide-treated net use was associated with 16%-17% lower odds of malaria infection (microscopy: aOR 0.83, 95% CI 0.78-0.88, p < 0.001; RDT: aOR 0.84, 95% CI 0.79-0.88, p < 0.001). Drinking water source and sanitation facility alone were not associated with diarrhoea. The main study limitations are the use of self-reported diarrhoea and ARI, as well as potential residual confounding by socioeconomic position, despite adjustments for household wealth and education.
In this study, we observed that poor housing, which includes inadequate drinking water and sanitation facility, is associated with health outcomes known to increase child mortality in SSA. Improvements to housing may be protective against a number of important childhood infectious diseases as well as poor growth outcomes, with major potential to improve children's health and survival across SSA.
Early exposure to enteropathogens has been associated with malnutrition in children in low-resource settings. However, the contribution of individual enteropathogens remains poorly defined. Molecular ...diagnostics offer an increase in sensitivity for detecting enteropathogens but have not been comprehensively applied to studies of malnutrition.
We sought to identify enteropathogens associated with malnutrition in Bangladesh.
Malnourished children weight-for-age
score (WAZ) <-2 aged 6-23 mo in Dhaka, Bangladesh, and identified by active community surveillance were enrolled as cases, and normal-weight children (WAZ >-1) of the same age and from the same community were enrolled as controls. Stools were collected at enrollment and, for cases, after a 5-mo nutritional intervention. Enrollment and follow-up stools were tested by quantitative polymerase chain reaction for 32 enteropathogens with the use of a custom-developed TaqMan Array Card.
Enteropathogen testing was performed on 486 cases and 442 controls upon enrollment and 365 cases at follow-up. At enrollment, the detection of enteroaggregative
(OR: 1.39; 95% CI: 1.05, 1.83),
spp. (OR: 1.46; 95% CI: 1.11, 1.91), heat-labile enterotoxin-producing
(OR: 1.55; 95% CI: 1.04, 2.33),
/enteroinvasive
(OR: 1.65; 95% CI: 1.10, 2.46), norovirus genogroup I (OR: 1.66; 95% CI: 1.23, 2.25), and
(OR: 1.73; 95% CI: 1.20, 2.49) were associated with malnourished cases, and the total burden of these pathogens remained associated with malnutrition after adjusting for sociodemographic factors. The number of these pathogens at follow-up was negatively associated with the change in WAZ during the intervention (-0.10 change in WAZ per pathogen detected; 95% CI: -0.14, -0.06), whereas the number at enrollment was positively associated with the change in WAZ (0.05 change in WAZ per pathogen detected; 95% CI: 0.00, 0.10).
A subset of enteropathogens was associated with malnutrition in this setting. Broad interventions designed to reduce the burden of infection with these pathogens are needed. This trial was registered at clinicaltrials.gov as NCT02441426.
Poor nutrition (substandard diet quantity and/or quality resulting in under- or overnutrition) and the lack of early learning opportunities contribute to the loss of developmental potential and ...life-long health and economic disparities among millions of children aged <5 y. Single-sector interventions representing either early child development (ECD) or nutrition have been linked to positive child development and/or nutritional status, and recommendations currently advocate for the development and testing of integrated interventions. We reviewed the theoretical and practical benefits and challenges of implementing integrated nutrition and ECD interventions along with the evidence for best practice and benefit-cost and concluded that the strong theoretical rationale for integration is more nuanced than the questions that the published empirical evidence have addressed. For example, further research is needed to 1) answer questions related to how integrated messaging influences caregiver characteristics such as well-being, knowledge, and behavior and how these influence early child nutrition and development outcomes; 2) understand population and nutritional contexts in which integrated interventions are beneficial; and 3) explore how varying implementation processes influence the efficacy, uptake, and cost-benefit of integrated nutrition and ECD interventions.
Summary We reviewed interventions that affect maternal and child undernutrition and nutrition-related outcomes. These interventions included promotion of breastfeeding; strategies to promote ...complementary feeding, with or without provision of food supplements; micronutrient interventions; general supportive strategies to improve family and community nutrition; and reduction of disease burden (promotion of handwashing and strategies to reduce the burden of malaria in pregnancy). We showed that although strategies for breastfeeding promotion have a large effect on survival, their effect on stunting is small. In populations with sufficient food, education about complementary feeding increased height-for-age Z score by 0·25 (95% CI 0·01–0·49), whereas provision of food supplements (with or without education) in populations with insufficient food increased the height-for-age Z score by 0·41 (0·05–0·76). Management of severe acute malnutrition according to WHO guidelines reduced the case-fatality rate by 55% (risk ratio 0·45, 0·32–0·62), and recent studies suggest that newer commodities, such as ready-to-use therapeutic foods, can be used to manage severe acute malnutrition in community settings. Effective micronutrient interventions for pregnant women included supplementation with iron folate (which increased haemoglobin at term by 12 g/L, 2·93–21·07) and micronutrients (which reduced the risk of low birthweight at term by 16% (relative risk 0·84, 0·74–0·95). Recommended micronutrient interventions for children included strategies for supplementation of vitamin A (in the neonatal period and late infancy), preventive zinc supplements, iron supplements for children in areas where malaria is not endemic, and universal promotion of iodised salt. We used a cohort model to assess the potential effect of these interventions on mothers and children in the 36 countries that have 90% of children with stunted linear growth. The model showed that existing interventions that were designed to improve nutrition and prevent related disease could reduce stunting at 36 months by 36%; mortality between birth and 36 months by about 25%; and disability-adjusted life-years associated with stunting, severe wasting, intrauterine growth restriction, and micronutrient deficiencies by about 25%. To eliminate stunting in the longer term, these interventions should be supplemented by improvements in the underlying determinants of undernutrition, such as poverty, poor education, disease burden, and lack of women's empowerment.
Malnutrition is a major contributor to mortality and is increasingly recognized as a cause of potentially lifelong functional disability. Yet, a rate-limiting step in achieving normal nutrition may ...be impaired absorptive function due to multiple repeated enteric infections. This is especially problematic in children whose diets are marginal. In malnourished individuals, the infections are even more devastating. This review documents the evidence that intestinal infections lead to malnutrition and that malnutrition worsens intestinal infections. The clinical data presented here derive largely from long-term cohort studies that are supported by controlled animal studies. Also reviewed are the mechanisms by which enteric infections lead to undernutrition and by which malnutrition worsens enteric infections, with implications for potential novel interventions. Further intervention studies are needed to document the relevance of these mechanisms and, most importantly, to interrupt the vicious diarrhea-malnutrition cycle so children may develop their full potential.
Kwashiorkor is an often-fatal type of severe acute malnutrition affecting hundreds of thousands of children annually, but whose etiology is still unknown. Evidence suggests inadequate sulfur amino ...acid (SAA) status may explain many signs of the condition but studies evaluating dietary protein intake in relation to the genesis of kwashiorkor have been conflicting. We know of no studies of kwashiorkor that have measured dietary SAAs.
We aimed to determine whether children in a population previously determined to have high prevalence of kwashiorkor high-prevalence population (HPP) have lower dietary intakes of SAAs than children in a low-prevalence population (LPP).
A cross-sectional census survey design of 358 children compared 2 previously identified adjacent populations of children 36–59 mo old in North Kivu Province of the Democratic Republic of the Congo. Data collected included urinary thiocyanate (SCN), cyanogens in cassava-based food products, recent history of illness, and a 24-h quantitative diet recall for the child.
The HPP and LPP had kwashiorkor prevalence of 4.5% and 1.7%, respectively. A total of 170 children from 141 households in the LPP and 169 children from 138 households in the HPP completed the study. A higher proportion of HPP children had measurable urinary SCN (44.8% compared with 29.4%, P < 0.01). LPP children were less likely to have been ill recently (26.8% compared with 13.6%, P < 0.01). Median IQR intake of SAAs was 32.4 22.9–49.3 mg/kg for the LPP and 29.6 18.1–44.3 mg/kg for the HPP (P < 0.05). Methionine was the first limiting amino acid in both populations, with the highest risk of inadequate intake found among HPP children (35.1% compared with 23.6%, P < 0.05).
Children in a population with a higher prevalence of kwashiorkor have lower dietary intake of SAAs than children in a population with a lower prevalence. Trial interventions to reduce incidence of kwashiorkor should consider increasing SAA intake, paying particular attention to methionine.
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