Determinants of Undernutrition among Children Admitted to a Pediatric Hospital in Port Sudan, Sudan.

Severe acute undernutrition (SAU) is still a crucial global health issue in the 0-59 months population, increasing the risk of mortality as well as of long-term consequences. In Sudan, 3.3 million children suffered from acute malnutrition between 2018 and 2019. This study was planned to evaluate, in the area of Port Sudan, the prevalence of acute undernutrition after the COVID-19 pandemic and to identify the most important factors favoring the development of acute undernutrition. The available clinical records of all the under-five children (n = 1012) admitted to the Port Sudan Emergency Pediatric Hospital from 1 February 2021 to 31 January 2022 were analyzed. The presence of wasting and kwashiorkor was assessed and children were categorized according to age, gender, place of residence, main reason for hospitalization, and underlying comorbidities. Acute undernutrition was evidenced in 493 (48.7%) children. Of them, only 16 (3.2%) were diagnosed with kwashiorkor. Children with SAU had a higher prevalence of acute gastroenteritis (p < 0.05) and parasitosis (p < 0.05). Infants aged 0-6 months were those with the lowest risk of undernutrition, whereas those aged 7-12 months were those with the greater risk. In these patients, multivariate analysis revealed that SAU and MAU were 2.5 times (OR 2.51; 95% CI, 1.79-3.55) and 5.5 times (OR 5.56; 95% CI, 2.59-18.7) higher. This study shows that the area of Port Sudan is still suffering from an alarming prevalence of severe wasting and the risk of developing acute undernutrition seems strictly related to the introduction of complementary feeding and tends to reduce with increasing age. Measures already in place to prevent acute malnutrition should be reinforced with improvement of mother education on child feeding.

Arm circumference for age, arm circumference and weight-for-height z-score for the evaluation of severe acute malnutrition: a retrospective cohort study in eastern Democratic Republic of Congo.

BACKGROUND: Little is known about the use of mid-upper arm circumference for age (MUACZ) for diagnosing of severe acute malnutrition (SAM) and its correlation with WHZ (weight-for-height Z-score) in an area endemic for severe acute malnutrition (SAM) and with a high prevalence of kwashiorkor. Our study aims to analyze the concordance between the diagnostic criteria of SAM in a region presenting these characteristics. METHODS: We analyzed a database of children admitted from 1987 to 2008 for the management of SAM in Eastern Democratic Republic of Congo. Anthropometric indicators (z-score) were calculated and classified into 3 categories according to WHO standards. Cohen's kappa coefficient (κ) was calculated to assess the concordance between these indicators. RESULTS: Out of the 9969 selected children aged 6 to 59 months, 30.2% had nutritional edema, 70.1% had a height-for-age (HAZ) z-score <-2, 11.5% WHZ<-3 z-score, 14.9% had a MUAC < 115 mm and 21.8% had a MUACZ <-3 z-score. With the classic combination WHZ and MUAC, 36% of children with SAM had both criteria at the same time and MUAC alone being the indicator that recruited more children with SAM (77%) compared with 65% with WHZ only. By replacing MUAC with MUACZ, 34% of SAM children fulfilled both criteria, WHZ and MUACZ. MUACZ alone recruited more children with SAM (88%) compared with 46% with WHZ alone. Considering these three indicators together, MUACZ remained the indicator that recruited more children with SAM (85%). WHZ and MUAC showed a moderate agreement [ κ (95% CI) = 0.408(0.392-0.424)], WHZ and MUACZ a weak agreement [ κ (95% CI) = 0.363(0.347-0.379)] and MUAC and MUACZ a good agreement [ κ (95% CI) = 0.604 (0.590-0.618)]. CONCLUSION: Adjusting MUAC according to age improves its effectiveness in identifying severe acute malnutrition. With low concordance, MUAC and WHZ remain complementary in our context. MUACZ proves to be crucial, especially in the presence of kwashiorkor and chronic malnutrition, becoming a valuable tool for assessing severe acute malnutrition in our context.

Kwashiorkor in an 8-Month-Old Infant Due to Homemade Formula Use.

INTRODUCTION: Kwashiorkor is a malnutrition syndrome most commonly seen in the United States among patients with malabsorptive conditions. While it is rare in otherwise healthy individuals, cases can develop where low nutritional literacy or unorthodox diets are a factor. CASE PRESENTATION: We present an 8-month-old infant who developed kwashiorkor after transitioning to homemade infant formula. DISCUSSION: This patient developed severe malnutrition due to consumption of homemade formula that did not meet nutritional standards. The recipe was promoted by an alternative health organization as a healthy option, and the difficulty in identifying reliable health information online also played a significant role. CONCLUSIONS: Families of young children face many challenges, particularly during the recent infant formula shortage. Maintaining strong relationships and open communication with trusted health care professionals is vital to combating health misinformation and helping patients and families navigate these challenges safely.

Protein malnutrition in BALB/C mice: A model mimicking clinical scenario of marasmic-kwashiorkor malnutrition.

Protein malnutrition continues to be a major global issue. A stable animal model to address protein malnutrition and its effect on various disease conditions is necessary. In the present study, we have formulated and standardized a low protein diet (LPD) to develop a protein malnutrition model using Balb/C mice. Healthy male Balb/C mice were weaned and exposed to LPD combinations while another group exposed to normal diet (18% protein). Animal survival, change in body weight, body mass index (BMI), biochemical parameters, antioxidant status, and liver histopathology were used to confirm the development of malnourished mice model (marasmic-kwashiorkor). Mice receiving 10% protein diet showed moderate weight gain, higher BMI, and no mortality compared to the 6% protein group. The former group showed remarkable differences in BMI, biochemical and antioxidant parameters. Further, histopathological changes against the normal group at weeks 20 and 30 confirmed the development of protein malnutrition in mice on 10% protein diet. The study confirms the development of a stable, economical, reproducible, and clinically relevant protein malnutrition model using the formulated 10% protein diet. Further, the model can be used for short and long-term studies to investigate the pathophysiology of malnutrition in any disease/condition.

Risk of Chronic Disease after an Episode of Marasmus, Kwashiorkor or Mixed-Type Severe Acute Malnutrition in the Democratic Republic of Congo: The Lwiro Follow-Up Study.

Background: Long-term impact of different forms of severe acute malnutrition (SAM) in childhood on the emergence of noncommunicable diseases (NCDs) is poorly known. Aim: To explore the association between subtypes of SAM during childhood, NCDs, and cardiovascular risk factors (CVRFs) in young adults 11 to 30 years after post-SAM nutritional rehabilitation. Methods: In this follow-up study, we investigated 524 adults (mean age 22 years) treated for SAM during childhood in eastern Democratic Republic of the Congo (DRC) between 1988 and 2007. Among them, 142 had a history of marasmus, 175 of kwashiorkor, and 207 had mixed-form SAM. These participants were compared to 407 aged- and sex-matched control adults living in the same community without a history of SAM. Our outcomes of interest were cardiometabolic risk markers for NCDs. Logistic and linear regressions models were sued to estimate the association between subtype of SAM in childhood and risk of NCDs. Results: Compared to unexposed, former mixed-type SAM participants had a higher adjusted ORs of metabolic syndrome [2.68 (1.18; 8.07)], central obesity [1.89 (1.11; 3.21)] and low HDL-C (High-density lipoprotein cholesterol) [1.52 (1.08; 2.62)]. However, there was no difference between groups in terms of diabetes, high blood pressure, elevated LDL-C (low-density lipoprotein cholesterol) and hyper TG (hypertriglyceridemia) and overweightness. Former mixed-type SAM participants had higher mean fasting glucose [3.38 mg/dL (0.92; 7.7)], reduced muscle strength [−3.47 kg (−5.82; −1.11)] and smaller hip circumference [−2.27 cm (−4.24; −0.31)] compared to non-exposed. Regardless of subtypes, SAM-exposed participants had higher HbA1c than unexposed (p < 0.001). Those with a history of kwashiorkor had cardiometabolic and nutritional parameters almost superimposable to those of unexposed. Conclusion: The association between childhood SAM, prevalence of NCDs and their CVRFs in adulthood varies according to SAM subtypes, those with mixed form being most at risk. Multicenter studies on larger cohorts of older participants are needed to elucidate the impact of SAM subtypes on NCDs risk.

Mechanisms of Kwashiorkor-Associated Immune Suppression: Insights From Human, Mouse, and Pig Studies.

Malnutrition refers to inadequate energy and/or nutrient intake. Malnutrition exhibits a bidirectional relationship with infections whereby malnutrition increases risk of infections that further aggravates malnutrition. Severe malnutrition (SM) is the main cause of secondary immune deficiency and mortality among children in developing countries. SM can manifest as marasmus (non-edematous), observed most often (68.6% of all malnutrition cases), kwashiorkor (edematous), detected in 23.8% of cases, and marasmic kwashiorkor, identified in ~7.6% of SM cases. Marasmus and kwashiorkor occur due to calorie-energy and protein-calorie deficiency (PCD), respectively. Kwashiorkor and marasmic kwashiorkor present with reduced protein levels, protein catabolism rates, and altered levels of micronutrients leading to uncontrolled oxidative stress, exhaustion of anaerobic commensals, and proliferation of pathobionts. Due to these alterations, kwashiorkor children present with profoundly impaired immune function, compromised intestinal barrier, and secondary micronutrient deficiencies. Kwashiorkor-induced alterations contribute to growth stunting and reduced efficacy of oral vaccines. SM is treated with antibiotics and ready-to-use therapeutic foods with variable efficacy. Kwashiorkor has been extensively investigated in gnotobiotic (Gn) mice and piglet models to understand its multiple immediate and long-term effects on children health. Due to numerous physiological and immunological similarities between pigs and humans, pig represents a highly relevant model to study kwashiorkor pathophysiology and immunology. Here we summarize the impact of kwashiorkor on children's health, immunity, and gut functions and review the relevant findings from human and animal studies. We also discuss the reciprocal interactions between PCD and rotavirus-a highly prevalent enteric childhood pathogen due to which pathogenesis and immunity are affected by childhood SM.

Childhood mortality during and after acute illness in Africa and south Asia: a prospective cohort study.

BACKGROUND: Mortality among children with acute illness in low-income and middle-income settings remains unacceptably high and the importance of post-discharge mortality is increasingly recognised. We aimed to explore the epidemiology of deaths among young children with acute illness across sub-Saharan Africa and south Asia to inform the development of interventions and improved guidelines. METHODS: In this prospective cohort study, we enrolled children aged 2-23 months with acute illness, stratified by nutritional status defined by anthropometry (ie, no wasting, moderate wasting, or severe wasting or kwashiorkor), who were admitted to one of nine hospitals in six countries across sub-Saharan Africa and south Asia between Nov 20, 2016, and Jan 31, 2019. We assisted sites to comply with national guidelines. Co-primary outcomes were mortality within 30 days of hospital admission and post-discharge mortality within 180 days of hospital discharge. A priori exposure domains, including demographic, clinical, and anthropometric characteristics at hospital admission and discharge, as well as child, caregiver, and household-level characteristics, were examined in regression and survival structural equation models. FINDINGS: Of 3101 children (median age 11 months [IQR 7-16]), 1120 (36·1%) had no wasting, 763 (24·6%) had moderate wasting, and 1218 (39·3%) had severe wasting or kwashiorkor. Of 350 (11·3%) deaths overall, 234 (66·9%) occurred within 30 days of hospital admission and 168 (48·0%) within 180 days of hospital discharge. 90 (53·6%) post-discharge deaths occurred at home. The proportion of children who died following discharge was relatively preserved across nutritional strata. Numerically large high-risk and low-risk groups could be disaggregated for early mortality and post-discharge mortality. Structural equation models identified direct pathways to mortality and multiple socioeconomic, clinical, and nutritional domains acting indirectly through anthropometric status. INTERPRETATION: Among diverse sites in Africa and south Asia, almost half of mortality occurs following hospital discharge. Despite being highly predictable, these deaths are not addressed in current guidelines. A fundamental shift to a child-centred, risk-based approach to inpatient and post-discharge management is needed to further reduce childhood mortality, and clinical trials of these approaches with outcomes of mortality, readmission, and cost are warranted. FUNDING: The Bill & Melinda Gates Foundation.

The effect of wasting and stunting during severe acute malnutrition in infancy on insulin sensitivity and insulin clearance in adult life.

Adults who had non-edematous severe acute malnutrition (SAM) during infancy (i.e., marasmus) have worse glucose tolerance and beta-cell function than survivors of edematous SAM (i.e., kwashiorkor). We hypothesized that wasting and/or stunting in SAM is associated with lower glucose disposal rate (M) and insulin clearance (MCR) in adulthood.We recruited 40 nondiabetic adult SAM survivors (20 marasmus survivors (MS) and 20 kwashiorkor survivors (KS)) and 13 matched community controls. We performed 150-minute hyperinsulinaemic, euglycaemic clamps to estimate M and MCR. We also measured serum adiponectin, anthropometry, and body composition. Data on wasting (weight-for-height) and stunting (height-for-age) were abstracted from the hospital records.Children with marasmus had lower weight-for-height z-scores (WHZ) (-3.8 ± 0.9 vs. -2.2 ± 1.4; P < 0.001) and lower height-for-age z-scores (HAZ) (-4.6 ± 1.1 vs. -3.4 ± 1.5; P = 0.0092) than those with kwashiorkor. As adults, mean age (SD) of participants was 27.2 (8.1) years; BMI was 23.6 (5.0) kg/m2. SAM survivors and controls had similar body composition. MS and KS and controls had similar M (9.1 ± 3.2; 8.7 ± 4.6; 6.9 ± 2.5 mg.kg-1.min-1 respectively; P = 0.3) and MCR. WHZ and HAZ were not associated with M, MCR or adiponectin even after adjusting for body composition.Wasting and stunting during infancy are not associated with insulin sensitivity and insulin clearance in lean, young, adult survivors of SAM. These data are consistent with the finding that glucose intolerance in malnutrition survivors is mostly due to beta-cell dysfunction.

One-carbon metabolism in children with marasmus and kwashiorkor.

BACKGROUND: Kwashiorkor is a childhood syndrome of edematous malnutrition. Its precise nutritional precipitants remain uncertain despite nine decades of study. Remarkably, kwashiorkor's disturbances resemble the effects of experimental diets that are deficient in one-carbon nutrients. This similarity suggests that kwashiorkor may represent a nutritionally mediated syndrome of acute one-carbon metabolism dysfunction. Here we report findings from a cross-sectional exploration of serum one-carbon metabolites in Malawian children. METHODS: Blood was collected from children aged 12-60 months before nutritional rehabilitation: kwashiorkor (N = 94), marasmic-kwashiorkor (N = 43) marasmus (N = 118), moderate acute malnutrition (N = 56) and controls (N = 46). Serum concentrations of 16 one-carbon metabolites were quantified using LC/MS techniques, and then compared across participant groups. FINDINGS: Twelve of 16 measured one-carbon metabolites differed significantly between participant groups. Measured outputs of one-carbon metabolism, asymmetric dimethylarginine (ADMA) and cysteine, were lower in marasmic-kwashiorkor (median µmol/L (± SD): 0·549 (± 0·217) P = 0·00045 & 90 (± 40) P < 0·0001, respectively) and kwashiorkor (0·557 (± 0·195) P < 0·0001 & 115 (± 50) P < 0·0001), relative to marasmus (0·698 (± 0·212) & 153 (± 42)). ADMA and cysteine were well correlated with methionine in both kwashiorkor and marasmic-kwashiorkor. INTERPRETATION: Kwashiorkor and marasmic-kwashiorkor were distinguished by evidence of one-carbon metabolism dysfunction. Correlative observations suggest that methionine deficiency drives this dysfunction, which is implicated in the syndrome's pathogenesis. The hypothesis that kwashiorkor can be prevented by fortifying low quality diets with methionine, along with nutrients that support efficient methionine use, such as choline, requires further investigation. FUNDING: The Hickey Family Foundation, the American College of Gastroenterology, the NICHD, and the USDA/ARS.

Dietary intake of sulfur amino acids and risk of kwashiorkor malnutrition in eastern Democratic Republic of the Congo.

BACKGROUND: 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. OBJECTIVES: 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). METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Secondary Kwashiorkor Disease in a Patient with Gastric Bypass Surgery and Short Gut Syndrome.

BACKGROUND Kwashiorkor disease is a subtype of severe acute protein malnutrition characterized by peripheral edema associated with hypoalbuminemia and ascites. It can result from both protein deficiency and protein loss. In resource-poor countries, the disease often is caused by inadequate dietary intake, but in resource-rich countries, it can be seen as a rare complication of severe malabsorption. CASE REPORT We present the case of a 60-year-old woman who presented with 1 week of progressive anasarca in the setting of decreased dietary intake and poor tolerance of total parenteral nutrition (TPN). She had a history of Roux-en-Y gastric bypass surgery which was complicated by a strangulated internal hernia that required an exploratory laparotomy and small bowel resection. She subsequently developed short gut syndrome with TPN dependence. Work-up revealed hypoalbuminemia with several micronutrient deficiencies consistent with secondary kwashiorkor disease. With a multidisciplinary approach that included Gastroenterology, Pharmacy, and Nutrition, she was treated with albumin, furosemide, nutritional supplementation, and ultimately rechallenged with TPN. At discharge, her swelling had improved, her weight had decreased, and her albumin improved to the normal range. CONCLUSIONS This case is a unique presentation of secondary kwashiorkor disease. In our patient, the combination of gastric bypass surgery and short gut syndrome with poor TPN tolerance likely led to severe protein malabsorption. This underscores the importance of recognizing the signs and symptoms of kwashiorkor disease and understanding the associated complications so that treatment can be instituted promptly. Furthermore, the case demonstrates how an interdisciplinary approach to management can increase the chance of a successful outcome.

Difference between kwashiorkor and marasmus: Comparative meta-analysis of pathogenic characteristics and implications for treatment.

Kwashiorkor and marasmus are two clinical syndromes observed in severe acute malnutrition. In this review, we highlighted the differences between these two syndromes by reviewing the data comparing kwashiorkor and marasmus in literature, combined with recent microbiological findings and meta-analysis. Depletion of antioxidants, vitamins and minerals were more severe in kwashiorkor than marasmus. This was consistent with the severe and uncontrolled oxidative stress associated with the depletion of gut anaerobes and the relative proliferation of aerotolerant gut pathogens. This relative proliferation and invasion of gut microbes belonging to the aerotolerant Proteobacteria phylum and pathogens suggested a specific microbial process critical in the pathogenesis of kwashiorkor. Liver mitochondrial and peroxisomal dysfunction could be secondary to toxic microbial compounds produced in the gut such as ethanol, lipopolysaccharides and endotoxins produced by Proteobacteria, particularly Klebsiella pneumoniae, and aflatoxin produced by Aspergillus species. The gut-liver axis alteration is characterized by oedema and a fatty and enlarged liver and was associated with a dramatic depletion of methionine and glutathione, an excessive level of free circulating iron and frequent lethal bacteraemia by enteric pathogens. This was consistent with the fact that antibiotics improved survival only in children with kwashiorkor but not marasmus. The specific pathogenic characteristics of kwashiorkor identified in this review open new avenues to develop more targeted and effective treatments for both marasmus and/or kwashiorkor. Urgent correction of plasma glutathione depletion, alongside supply of specific essential amino acids, particularly methionine and cysteine, early detection of pathogens and an antibiotic more efficient than amoxicillin in supressing gut Proteobacteria including K. pneumoniae, and probiotics to restore the human gut anaerobic mature microbiota could save many more children with kwashiorkor.