A New Murine Undernutrition Model Based on Complementary Feeding of Undernourished Children Causes Damage to the Morphofunctional Intestinal Epithelium Barrier.

BACKGROUND: Complementary feeding is critical in establishing undernutrition. However, experimental undernourished diets do not represent the amount of nutrients in the complementary diets of undernourished children. OBJECTIVES: To develop, validate, and evaluate the impact of a new murine model of undernutrition on the intestinal epithelium, based on the complementary diet of undernourished children from 7 countries with low-socioeconomic power belonging to the Malnutrition-Enteric Diseases (MAL-ED) cohort study. METHODS: We used the difference in the percentage of energy, macronutrients, fiber and zinc in the complementary diet of children without undernutrition compared with stunting (height-for-age Z-score < -2) for the MAL-ED diet formulation. Subsequently, C57BL/6 mice were fed a control diet (AIN-93M diet) or MAL-ED diet for 28 d. Weight was measured daily; body composition was measured every 7 d; lactulose:mannitol ratio (LM) and morphometry were evaluated on days 7 and 28; the cotransport test and analysis of intestinal transporters and tight junctions were performed on day 7. RESULTS: The MAL-ED diet presented -8.03% energy, -37.46% protein, -24.20% lipid, -10.83% zinc, +5.93% carbohydrate, and +45.17% fiber compared with the control diet. This diet rapidly reduced weight gain and compromised body growth and energy reserves during the chronic period (P < 0.05). In the intestinal epithelial barrier, this diet caused an increase in the LM (P < 0.001) and reduced (P < 0.001) the villous area associated with an increase in FAT/CD36 in the acute period and increased (P < 0.001) mannitol excretion in the chronic period. CONCLUSIONS: The MAL-ED diet induced undernutrition in mice, resulting in acute damage to the integrity of the intestinal epithelial barrier and a subsequent increase in the intestinal area during the chronic period. This study introduces the first murine model of undernutrition for the complementary feeding phase, based on data from undernourished children in 7 different countries.

A pilot study using hospital surveillance and a birth cohort to investigate enteric pathogens and malnutrition in children, Dili, Timor-Leste.

In low-to-middle-income countries (LMICs), enteric pathogens contribute to child malnutrition, affecting nutrient absorption, inducing inflammation, and causing diarrhoea. This is a substantial problem in LMICs due to high disease burden, poor sanitation and nutritional status, and the cyclical nature of pathogen infection and malnutrition. This relationship remains understudied in Timor-Leste. In our pilot study of enteric pathogens and malnutrition in Dili, Timor-Leste (July 2019-October 2020), we recruited 60 infants in a birth cohort from Hospital Nacional Guido Valadares (HNGV) with up to four home visits. We collected faecal samples and details of demographics, anthropometrics, diet and food practices, and animal husbandry. Additionally, we collected faecal samples, diagnostics, and anthropometrics from 160 children admitted to HNGV with a clinical diagnosis of severe diarrhoea or severe acute malnutrition (SAM). We tested faeces using the BioFire® FilmArray® Gastrointestinal Panel. We detected high prevalence of enteric pathogens in 68.8% (95%CI 60.4-76.2%) of infants at home, 88.6% of SAM cases (95%CI 81.7-93.3%) and 93.8% of severe diarrhoea cases (95%CI 67.7-99.7%). Diarrhoeagenic Escherichia coli and Campylobacter spp. were most frequently detected. Pathogen presence did not significantly differ in birth cohort diarrhoeal stool, but hospital data indicated associations between Salmonella and Shigella and diarrhoea. We observed wasting in 18.4% (95%CI 9.2-32.5%) to 30.8% (95%CI 17.5-47.7%) of infants across home visits, 57.9% (95%CI 34.0-78.9%) of severe diarrhoea cases, and 92.5% (95%CI 86.4-96.2%) of SAM cases. We associated bottle feeding with increased odds of pathogen detection when compared with exclusive breastfeeding at home (OR 8.3, 95%CI 1.1-62.7). We detected high prevalence of enteric pathogens and signs of malnutrition in children in Dili. Our pilot is proof of concept for a study to fully explore the risk factors and associations between enteric pathogens and malnutrition in Timor-Leste.

Identifying factors associated with child malnutrition in Ghana: a cross-sectional study using Bayesian multilevel ordinal logistic regression approach.

OBJECTIVE: In developing countries, malnutrition is a noteworthy concern related to the well-being of people, and this study aimed to determine the factors that affect malnutrition among children below 5 years in Ghana. DESIGN: The study used a secondary data source, specifically the Ghanaian Multiple Indicator Cluster Survey Six (MICS 6), which was conducted by the Ghana Statistical Service in 2017-2018. The MICS data are hierarchical, as children are categorised within households, and households are further grouped within a higher cluster, violating the independence assumption that must be addressed in the analyses. This study used a Bayesian multilevel ordinal logistic regression to model, identify and analyse the factors linked to child malnutrition in Ghana. SETTING: The setting of the study was the household level across the previous 10 administrative regions in Ghana. PARTICIPANTS: Data for 8875 children under 5 years were used for the study. The data were gathered from households in all 10 administrative regions of Ghana using a sampling procedure consisting of stratification and random selection to ensure national representation. RESULTS: The results showed that the Northern Region of Ghana had the highest occurrence rate of severe and moderate malnutrition, and factors such as the count of children's books or picture books, whether the child experienced fever in the last 2 weeks, age and sex of the child, and the child's household wealth index quintile were strongly linked to malnutrition among Ghanaian children. CONCLUSION: These findings underscore the intricate interplay of factors contributing to child nutrition in Ghana and suggest that addressing malnutrition necessitates a comprehensive approach that considers factors such as access to healthcare and reading materials, household wealth, and other social and environmental factors.

Interlinkages between Climate Change and Food Systems: The Impact on Child Malnutrition-Narrative Review.

The pandemics of obesity, undernutrition, and climate change represent severe threats to child health. They co-occur; interact with each other to produce sequelae at biological, psychological, or social levels; and share common underlying drivers. In this paper, we review the key issues concerning child diet and nutritional status, focusing on the interactions with climate and food systems. Inadequate infant and young child feeding practices, food insecurity, poverty, and limited access to health services are the leading causes of malnutrition across generations. Food system industrialization and globalization lead to a double burden of malnutrition, whereby undernutrition (i.e., stunting, wasting, and deficiencies in micronutrients) coexists with overweight and obesity, as well as to harmful effects on climate. Climate change and the COVID-19 pandemic are worsening child malnutrition, impacting the main underlying causes (i.e., household food security, dietary diversity, nutrient quality, and access to maternal and child health), as well as the social, economic, and political factors determining food security and nutrition (livelihoods, income, infrastructure resources, and political context). Existing interventions have the potential to be further scaled-up to concurrently address undernutrition, overnutrition, and climate change by cross-cutting education, agriculture, food systems, and social safety nets. Several stakeholders must work co-operatively to improve global sustainable nutrition.

How Can Nutrition Research Better Reflect the Relationship Between Wasting and Stunting in Children? Learnings from the Wasting and Stunting Project.

Childhood wasting and stunting affect large numbers of children globally. Both are important risk factors for illness and death yet, despite the fact that these conditions can share common risk factors and are often seen in the same child, they are commonly portrayed as relatively distinct manifestations of undernutrition. In 2014, the Wasting and Stunting project was launched by the Emergency Nutrition Network. Its aim was to better understand the complex relationship and associations between wasting and stunting and examine whether current separations that were apparent in approaches to policy, financing, and programs were justified or useful. Based on the project's work, this article aims to bring a wasting and stunting lens to how research is designed and financed in order for the nutrition community to better understand, prevent, and treat child undernutrition. Discussion of lessons learnt focuses on the synergy and temporal relationships between children's weight loss and linear growth faltering, the proximal and distal factors that drive diverse forms of undernutrition, and identifying and targeting people most at risk. Supporting progress in all these areas requires research collaborations across interest groups that highlight the value of research that moves beyond a focus on single forms of undernutrition, and ensures that there is equal attention given to wasting as to other forms of malnutrition, wherever it is present.

Association between water, sanitation and hygiene (WASH) and child undernutrition in Ethiopia: a hierarchical approach.

BACKGROUND: Undernutrition is a significant public health challenge and one of the leading causes of child mortality in a wide range of developing countries, including Ethiopia. Poor access to water, sanitation, and hygiene (WASH) facilities commonly contributes to child growth failure. There is a paucity of information on the interrelationship between WASH and child undernutrition (stunting and wasting). This study aimed to assess the association between WASH and undernutrition among under-five-year-old children in Ethiopia. METHODS: A secondary data analysis was undertaken based on the Ethiopian Demographic and Health Surveys (EDHS) conducted from 2000 to 2016. A total of 33,763 recent live births extracted from the EDHS reports were included in the current analysis. Multilevel logistic regression models were used to investigate the association between WASH and child undernutrition. Relevant factors from EDHS data were identified after extensive literature review. RESULTS: The overall prevalences of stunting and wasting were 47.29% [95% CI: (46.75, 47.82%)] and 10.98% [95% CI: (10.65, 11.32%)], respectively. Children from households having unimproved toilet facilities [AOR: 1.20, 95% CI: (1.05,1.39)], practicing open defecation [AOR: 1.29, 95% CI: (1.11,1.51)], and living in households with dirt floors [AOR: 1.32, 95% CI: (1.12,1.57)] were associated with higher odds of being stunted. Children from households having unimproved drinking water sources were significantly less likely to be wasted [AOR: 0.85, 95% CI: (0.76,0.95)] and stunted [AOR: 0.91, 95% CI: (0.83, 0.99)]. We found no statistical differences between improved sanitation, safe disposal of a child's stool, or improved household flooring and child wasting. CONCLUSION: The present study confirms that the quality of access to sanitation and housing conditions affects child linear growth indicators. Besides, household sources of drinking water did not predict the occurrence of either wasting or stunting. Further longitudinal and interventional studies are needed to determine whether individual and joint access to WASH facilities was strongly associated with child stunting and wasting.

Child undernutrition and associated factors among children 6-23 months old in largely food insecure areas of rural Ethiopia.

Child malnutrition is the leading public health problem in Sub-Saharan Africa, resulting in poor health and economic losses. Ethiopia has one of the highest child undernutrition rates in the world that occurs to multifaceted factors, including food insecurity. Thus, we performed a cross-sectional study to assess the prevalence and risk factors for child undernutrition in largely food insecure areas of Ethiopia. Data were collected from 354 mother-child pairs from the Siraro district. Both bivariate and multivariate logistic regression was used for statistical analysis. Variables with a P-value of <0⋅05 in multivariate analysis were used to detect statistical significance at a 95 % confidence level. About 67 % of households are food insecure. The prevalence of stunting wasting and underweight were 42⋅7, 9⋅9 and 27⋅7 %, respectively. Female gender, higher age of the child (12-23 months v. 6-11 months), living in a household with five or more siblings, not getting therapeutic zinc supplement at least once, inadequate diet diversity, lack of growth monitoring service, and maternal own income increases the likelihood of child undernutrition. It can be concluded that child undernutrition is a severe public health problem in the study area. Improving primary healthcare services related to zinc supplementation, growth monitoring and promotion, and improving infant and child feeding practices can be considered as a strategy to address the problem.

Death in severely malnourished hospitalized children presenting with diarrhea and vomiting.

INTRODUCTION: There is lack of data on outcomes of severely malnourished children who are hospitalized with concomitant diarrhea and vomiting. We sought to evaluate outcomes of such children. METHODOLOGY: In this retrospective chart review, we used electronic databases to evaluate children aged 0-59 months and admitted to the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh, with diarrhea and severe malnutrition between April 2011 and August 2012. Outcomes of children with and without vomiting were compared. The primary outcome was death. A probability of ≤ 0.05 was considered statistically significant. RESULTS: Out of 306 enrolled children, 51 (17%) had vomiting and 255 (83%) did not have vomiting. A total of 31 (10%) children died, 12 (24%) of them had vomiting and 19 (8%) did not have vomiting. Death was significantly higher in severely malnourished diarrheal children with vomiting (12/51 (24%)) compared to those without vomiting (19/255 (8%)) (Relative risk [RR] 2.73, 95% confidence interval [CI] 1.61-4.64; p < 0.001). We used Log linear bi-nominal regression after adjusting for potential confounders such as metabolic acidosis and hypoglycemia, and found that vomiting was significantly associated with deaths in severely malnourished diarrheal children (RR 1∙89, 95% CI 1.01-1.33; p = 0.05). CONCLUSIONS: Our analysis showed that children with diarrhea and severe malnutrition who had vomiting during hospitalization were at a higher risk of death compared to those without vomiting. The results underscore the importance of prompt identification and management of vomiting to reduce deaths in such children.

Nexus between maternal underweight and child anthropometric status in South and South-East Asian countries.

OBJECTIVES: Maternal underweight and childhood malnutrition are life-threatening public health concerns in several South and South-East Asian nations. The aim of this study was to better design interventions and prevent malnutrition of children in the region by exploring the association of maternal underweight with children's anthropometric status. METHODS: The Demographic and Health Survey's (DHS) most recent nationally representative data from eight South and South-East Asian states, collected between 2014 and 2018, were pooled for the present study. A multivariable logistic regression model was designed to explore the association between maternal underweight and child anthropometric status. Owing to the hierarchical structure of the DHS data, the study also employed the multilevel logistic regression technique. RESULTS: Among the total participants (N = 213 730), 22.66% of women were found to be underweight, whereas 39.03%, 35.88%, and 22.11% of their children had stunting, underweight, and wasting, respectively. The logistic regression model showed that the children from underweight mothers were 1.27 (95% confidence interval [CI]. 1.24-1.30), 1.69 (95% CI, 1.65-1.73), and 1.48 (95% CI, 1.45-1.52) times more likely to experience stunting, underweight, and wasting, respectively, than those with healthy-weight mothers. The significant association between maternal underweight and stunting, underweight, as well as wasting was additionally established by the multilevel logistic regression analysis. CONCLUSIONS: Findings indicate that maternal underweight is positively associated with children's anthropometric status, such as stunting, underweight, and wasting. The information from this research will guide actors and policymakers to scale up interventions with all-inclusive nutritional issues and promote healthier weight status among mothers to ensure higher odds of healthier anthropometric status in their children in the South and South-East Asian countries.

Risk factors associated with the coexistence of stunting, underweight, and wasting in children under 5 from 31 sub-Saharan African countries.

OBJECTIVE: This study investigated the risk factors associated with the coexistence of stunting, underweight, and wasting among children under age 5 in sub-Saharan Africa (SSA). DESIGN: Data of 127, 487 under-5 children from 31 countries in SSA were pooled from the Demographic and Health Surveys collected between 2010 and 2019. We examined the risk of coexistence of stunting, underweight, and wasting using multinomial logistic regression models. The results were presented using relative risk ratios (RRR) with corresponding confidence intervals (CIs). SETTING: Thirty-one sub-Saharan African countries. PARTICIPANTS: Children under age 5. OUTCOME MEASURES: The outcome variables were three child anthropometrics: stunting (height-for-age z-scores); underweight (weight-for-age z-scores) and wasting (weight-for-height z-scores). RESULTS: The prevalence of coexistence of stunting, underweight, and wasting varied across countries, with the highest (12.14%) and lowest (0.58%) prevalences of coexistence of stunting, underweight and wasting in Benin and Gambia respectively. The risk of coexistence of the three indicators of undernutrition was higher among children aged 1 year (RRR=3.714; 95% CI 3.319 to 4.156) compared with those aged 0. The risk of coexistence of the three dimensions was lower among female children (RRR=0.468 95% CI 0.420 to 0.51), but higher for those with small size at birth (RRR=3.818; CI 3.383 to 4.308), those whose mothers had no education (RRR=3.291; 95% CI 1.961 to 5.522), not working (RRR=1.195; 95% CI 1.086 to 1.314), had no antenatal visits during pregnancy (RRR=1.364; 95% CI 1.20 to 1.541), children delivered at home (RRR=1.372; CI 1.232 to 1.529), those from poor households (RRR=1.408; 95% CI 1.235 to 1.605), those whose mothers had no access to media (RRR=1.255; 95% CI 1.144 to 1.377) and living in households with an unimproved toilet facility (RRR=1.158; 95% CI 1.032 to 1.300). CONCLUSIONS: Findings suggest the urgent need for consideration of the coexistence of stunting, wasting and underweight among under-5 children in policy design and programming of interventions to eradicate child malnutrition in SSA. In the short-term, national-level policies and interventions need to be well tailored considering the compositional characteristics.

Azithromycin versus Amoxicillin and Malarial Parasitemia among Children with Uncomplicated Severe Acute Malnutrition: A Randomized Controlled Trial.

Antibiotics are recommended by the WHO as part of the management of uncomplicated severe acute malnutrition in children. We evaluated whether azithromycin, an antibiotic with antimalarial properties, improved malarial parasitemia outcomes in children with severe acute malnutrition compared with amoxicillin, an antibiotic commonly used for severe acute malnutrition that does not have antimalarial properties. Total of 301 children were randomized (1:1) to a single oral dose of azithromycin or a 7-day course of amoxicillin and followed for 8 weeks. We found no significant evidence that children receiving azithromycin had improved parasitemia outcomes relative to amoxicillin. Although azithromycin may have advantages over amoxicillin in terms of dosing and administration for uncomplicated severe acute malnutrition, it may not yield additional benefit for malaria outcomes.

Intraindividual Double Burden of Malnutrition in Chinese Children and Adolescents Aged 6-17 Years: Evidence from the China Health and Nutrition Survey 2015.

Studies on the intraindividual double burden of malnutrition (DBM) among Chinese children and adolescents were lacking. This study aimed to analyze the prevalence of intraindividual DBM defined as the coexistence of overweight/obesity and dietary micronutrient intake insufficiency and investigate dietary micronutrient intake in Chinese children and adolescents. Using data from the 2015 China Health and Nutrition Survey (CHNS), 1555 children and adolescents aged 6 to 17 years were selected as the subjects. We referred to China Food Composition to calculate the intakes of 11 selected dietary micronutrients from diet data collected by consecutive three days of 24 h recalls combined with household weighing of seasonings. We used the Chinese estimated average requirement (EARs) as a cutoff to define the dietary micronutrients deficiency, and applied the body-mass-index-for-age Z-scores (BAZ) of World Health Organization (WHO) child growth standards to define the category of body weight. Among the subjects in present study, the prevalence of overweight and obesity was 15.43% and 11.06%, respectively, and 26.24% of the subjects had undergone intraindividual DBM. The results suggest that the prevalence of intraindividual DBM and dietary micronutrients deficiency in Chinese children and adolescents is high.

Gut integrity and duodenal enteropathogen burden in undernourished children with environmental enteric dysfunction.

Environmental enteric dysfunction (EED) is a subclinical condition of intestinal inflammation, barrier dysfunction and malabsorption associated with growth faltering in children living in poverty. This study explores association of altered duodenal permeability (lactulose, rhamnose and their ratio) with higher burden of enteropathogen in the duodenal aspirate, altered histopathological findings and higher morbidity (diarrhea) that is collectively associated with linear growth faltering in children living in EED endemic setting. In a longitudinal birth cohort, 51 controls (WHZ > 0, HAZ > -1.0) and 63 cases (WHZ< -2.0, refractory to nutritional intervention) were recruited. Anthropometry and morbidity were recorded on monthly bases up to 24 months of age. Dual sugar assay of urine collected after oral administration of lactulose and rhamnose was assessed in 96 children from both the groups. Duodenal histopathology (n = 63) and enteropathogen analysis of aspirate via Taqman array card (n = 60) was assessed in only cases. Giardia was the most frequent pathogen and was associated with raised L:R ratio (p = 0.068). Gastric microscopy was more sensitive than duodenal aspirate in H. pylori detection. Microscopically confirmed H. pylori negatively correlated with HAZ at 24 months (r = -0.313, p = 0.013). Regarding histopathological parameters, goblet cell reduction significantly correlated with decline in dual sugar excretion (p< 0.05). Between cases and controls, there were no significant differences in the median (25th, 75th percentile) of urinary concentrations (µg/ml) of lactulose [27.0 (11.50, 59.50) for cases vs. 38.0 (12.0, 61.0) for controls], rhamnose [66.0 (28.0, 178.0) vs. 86.5 (29.5, 190.5)] and L:R ratio [0.47 (0.24, 0.90) vs. 0.51 (0.31, 0.71)] respectively. In multivariable regression model, 31% of variability in HAZ at 24 months of age among cases and controls was explained by final model including dual sugars. In conclusion, enteropathogen burden is associated with altered histopathological features and intestinal permeability. In cases and controls living in settings of endemic enteropathy, intestinal permeability test may predict linear growth. However, for adoption as a screening tool for EED, further validation is required due to its complex intestinal pathophysiology.

Inappropriate diet and fatal malnutrition in a 10-year-old child fed only infant formula throughout life: Novel pathological diagnostic criterion for starvation via lipophagy.

Fatal starvation is rarely seen in developed countries; when it occurs, it may be associated with medicolegal problems. Forensic pathologists are required to determine leading causes of death and provide opinions on the influence of starvation, especially in cases of suspected child abuse. Recently, starvation-induced steatosis was suggested to be regulated by lipophagy. Here, we report an extremely rare case of death by malnutrition of a 10-year-old boy, who was fed only infant formula throughout his life. The deceased presented with severe hepatic steatosis, probably related to prolonged malnutrition. Fatty liver changes, with deposition of small lipid droplets deposited in the peripheral lobules. High levels of P62 protein (overexpression of which indicates an autophagy impairment) were seen around the central vein region, whereas light-chain-3 (LC3) protein (an indicator of lipophagy activation) was unremarkable. Thus, in our case, impaired lipophagy influenced starvation-induced steatosis. To our knowledge, this article is the first to evaluate the application of lipophagy in forensic investigations as an objective diagnostic criterion.

Severe acute malnutrition in childhood, chronic diseases, and human capital in adulthood in the Democratic Republic of Congo: the Lwiro Cohort Study.

BACKGROUND: Little is known about the long-term outcome of children treated for severe acute malnutrition (SAM) after nutritional rehabilitation. OBJECTIVES: To explore the association between SAM in childhood, noncommunicable diseases (NCDs), and low human capital in adulthood. METHODS: We identified 524 adults (median age: 22 y) who were treated for SAM during childhood in Eastern Democratic Republic of Congo between 1988 and 2007. They were compared with 407 community unexposed age- and sex-matched subjects with no history of SAM. The variables of interest were cardiometabolic risk markers for NCDs and human capital. For the comparison, we used linear and logistic regressions to estimate the association between SAM in childhood and the risk of NCDs and ordinal logistic regression for the human capital. RESULTS: Compared with unexposed subjects, the exposed participants had a higher waist circumference [1.2 (0.02, 2.3) cm; P = 0.015], and a larger waist-to-height ratio [0.01 (0.01, 0.02) cm; P < 0.001]. On the other hand, they had a smaller hip circumference [-1.5 (-2.6, -0.5) cm; P = 0.021]. Regarding cardiometabolic markers for NCDs, apart from a higher glycated hemoglobin (HbA1c) [0.4 (0.2, 0.6); P < 0.001], no difference was observed in other cardiometabolic markers for NCD between the 2 groups. Compared with unexposed participants, exposed participants had a higher risk of metabolic syndrome (crude OR: 2.35; 95% CI: 1.22, 4.54; P = 0.010) and visceral obesity [adjusted OR: 1.44 (1.09, 1.89); P = 0.001]. The prevalence of hypertension, diabetes, overweight, and dyslipidaemia was similar in both groups. Last, the proportion of malnutrition survivors with higher socioeconomic status level was lower. CONCLUSION: SAM during childhood was associated with a high risk of NCDs and lower human capital in adulthood. Thus, policymakers and funders seeking to fight the global spread of NCDs in adults in low-resource settings should consider the long-term benefit of reducing childhood SAM as a preventive measure to reduce the socioeconomic burden attributable to NCDs.

Examining Associations of HIV and Iron Status with Nutritional and Inflammatory Status, Anemia, and Dietary Intake in South African Schoolchildren.

The etiology of multifactorial morbidities such as undernutrition and anemia in children living with the human immunodeficiency virus (HIV) (HIV+) on antiretroviral therapy (ART) is poorly understood. Our objective was to examine associations of HIV and iron status with nutritional and inflammatory status, anemia, and dietary intake in school-aged South African children. Using a two-way factorial case-control design, we compared four groups of 8 to 13-year-old South African schoolchildren: (1) HIV+ and low iron stores (inflammation-unadjusted serum ferritin ≤ 40 µg/L), n = 43; (2) HIV+ and iron sufficient non-anemic (inflammation-unadjusted serum ferritin > 40 µg/L, hemoglobin ≥ 115 g/L), n = 41; (3) children without HIV (HIV-ve) and low iron stores, n = 45; and (4) HIV-ve and iron sufficient non-anemic, n = 45. We assessed height, weight, plasma ferritin (PF), soluble transferrin receptor (sTfR), plasma retinol-binding protein, plasma zinc, C-reactive protein (CRP), α-1-acid glycoprotein (AGP), hemoglobin, mean corpuscular volume, and selected nutrient intakes. Both HIV and low iron stores were associated with lower height-for-age Z-scores (HAZ, p < 0.001 and p = 0.02, respectively), while both HIV and sufficient iron stores were associated with significantly higher CRP and AGP concentrations. HIV+ children with low iron stores had significantly lower HAZ, significantly higher sTfR concentrations, and significantly higher prevalence of subclinical inflammation (CRP 0.05 to 4.99 mg/L) (54%) than both HIV-ve groups. HIV was associated with 2.5-fold higher odds of iron deficient erythropoiesis (sTfR > 8.3 mg/L) (95% CI: 1.03-5.8, p = 0.04), 2.7-fold higher odds of subclinical inflammation (95% CI: 1.4-5.3, p = 0.004), and 12-fold higher odds of macrocytosis (95% CI: 6-27, p < 0.001). Compared to HIV-ve counterparts, HIV+ children reported significantly lower daily intake of animal protein, muscle protein, heme iron, calcium, riboflavin, and vitamin B12, and significantly higher proportions of HIV+ children did not meet vitamin A and fiber requirements. Compared to iron sufficient non-anemic counterparts, children with low iron stores reported significantly higher daily intake of plant protein, lower daily intake of vitamin A, and lower proportions of inadequate fiber intake. Along with best treatment practices for HIV, optimizing dietary intake in HIV+ children could improve nutritional status and anemia in this vulnerable population. This study was registered at clinicaltrials.gov as NCT03572010.

Biomarkers of environmental enteric dysfunction are differently associated with recovery and growth among children with moderate acute malnutrition in Sierra Leone.

BACKGROUND: Environmental enteric dysfunction (EED) may influence growth during and recovery from moderate acute malnutrition (MAM), however, biomarkers to assess these relations have yet to be identified. OBJECTIVES: The objectives of this study were to: 1) develop a score for EED based on host fecal mRNA transcripts, 2) compare biomarkers of EED with each other, and 3) examine associations between the EED biomarkers and recovery from MAM and growth outcomes. METHODS: In a cohort of 520 Sierra Leonean MAM children, biomarkers of EED included the lactulose: mannitol (L: M) test, 15 host fecal mRNA transcripts, and host fecal proteins [α-1-antitrypsin (AAT), myeloperoxidase (MPO), neopterin (NEO)]. Anthropometry data were also collected and z scores were computed for length-for-age (LAZ) and weight-for-length (WLZ). Recovery from MAM was defined as midupper arm circumference ≥12.5 cm. Factor analysis was used to identify EED scores using the mRNA transcripts, and mixed effects regression was conducted to test for associations. RESULTS: The 15 host fecal mRNA transcripts were clustered into 3 scores: gut inflammation (GI) score, gut structure (GS) score, and gut defense (GD) score. We found agreement between certain inflammation markers (GI score and MPO), and permeability markers (GS score and AAT; AAT and the L: M excretion ratio). Antimicrobial gut defense (GD score) was inversely associated with percent lactulose excreted, a measure of intestinal permeability. LAZ (ß: -0.08; 95% CI: -0.14, -0.02) and WLZ (ß: -0.03; 95% CI: -0.06, -0.01) were negatively associated with GI score. A high GD score (ß: 0.36; 95% CI: 0.08, 0.64) and low AAT (ß: -1.35; 95% CI: -2.35, -0.36) were associated with recovery from MAM. CONCLUSIONS: Scores derived from host fecal mRNA transcript variably correlated with the L: M test and host fecal proteins. Markers of intestinal inflammation, permeability, and defense were associated with growth outcomes and recovery from MAM.

Environmental, Metabolic, and Inflammatory Factors Converge in the Pathogenesis of Moderate Acute Malnutrition in Children: An Observational Cohort Study.

Acute malnutrition affects more than 50 million children worldwide. These children are at an increased risk of morbidity and mortality from infectious disease. However, the pathogenesis of acute malnutrition and mechanisms underlying the increased risk and poor outcomes from infection are not well understood. Our objective was to identify differences in inflammation and inflammatory responses between children with moderate acute malnutrition (MAM) and healthy controls (HCs), and search for environmental, pathophysiological, and metabolic factors that may influence this response. Sixteen children with MAM and 16 HCs aged 18-36 months were studied in Nairobi, Kenya. None of the children had symptoms of an infectious disease (fever, diarrhea, or cough) in the 2 weeks before enrollment and sample collection. Demographic and health data were provided by their primary caregivers. Blood samples were collected to measure various biomarkers and the response to an inflammatory stimulus. Children with MAM were more frequently from households with contaminated water, crowding, and unstable income sources. They also had increases in basal inflammation, circulating bacterial lipopolysaccharide (LPS), markers of intestinal damage, and an exaggerated whole blood inflammatory response to LPS. Metabolic changes in children with MAM led to increased plasma levels of long-chain fatty acids, which were found to contribute to the pro-inflammatory state. These exploratory findings suggest convergence of multiple factors to promote dysregulated inflammatory responses and prompt several mechanistic hypotheses that can be pursued to better understand the pathogenesis of MAM.

A cohort analysis of survival and outcomes in severely anaemic children with moderate to severe acute malnutrition in Malawi.

INTRODUCTION: Moderate to severe acute malnutrition (SAM/MAM) and severe anaemia are important and associated co-morbidities in children aged less than five years. Independently, these two morbidities are responsible for high risk of in-hospital and post-discharge deaths and hospital readmissions. The primary objective of this study is to investigate the risk of death among severely anaemic children with moderate to severe acute malnutrition compared to children with severe anaemia alone. METHODS: This was a retrospective analysis of data collected from a large prospective study that was investigating severe anaemia in children aged less than 5 years old. The study was conducted at Queen Elizabeth Central Hospital in Blantyre and Chikhwawa district hospital in southern Malawi. Children aged less than five years old; with severe anaemia were screened and enrolled. Each child was followed up for eighteen months at one, three, six, twelve and eighteen months after enrolment. Data were analysed using STATA 15. RESULTS: Between July 2002 and July 2004, 382 severely anaemic children were enrolled in the main study. A total of 52 children were excluded due to missing anthropometric data. Out of the 330 included, 53 children were moderately to severely malnourished and 277 were not. At the end of the 18-month follow period, 28.3% of children with MAM/SAM died compared to 13% of children without MAM/SAM (RR 2.1, CI 0.9-4.2, p = 0.03). Similarly, children with moderate to severe malnutrition reported a significantly higher number of malaria infection cases (33.9%) compared to children with severe anaemia alone (27.9%, p = 0.02). However, the number of hospitalizations and recurrence of severe anaemia was similar and not statistically significant between the two groups (RR 0.8 (0.4-1.4), p = 0.6 and RR 1.1 (0.3-2.8), p = 0.8). CONCLUSION: Among children with severe anaemia, those who also had moderate to severe malnutrition had a twofold higher risk of dying compared to those who did not. It is therefore crucial to investigate acute malnutrition among severely anaemic children, as this might be treatable factor associated with high mortality.