Corn-Soy-Blend Fortified with Phosphorus to Prevent Refeeding Hypophosphatemia in Undernourished Piglets.

BACKGROUND: Phosphorus (P) levels in refeeding diets are very important as undernourished children are at risk of hypophosphatemia during refeeding. For this reason, conventional corn-soy-blends (CSB) have been reformulated by the World Food Programme to obtain a mono-calcium-phosphate fortified product (CSB+) and a product further fortified with skim milk powder (CBS++). METHODS: Using a piglet model of undernourished children, we hypothesized that feeding of CSB+, CSB++ or CSB+ with added whey permeate (CSB+/wp) would help to prevent refeeding hypophosphatemia. Pigs were weaned at 4 weeks of age and undernutrition was induced with a nutritionally inadequate pure maize diet for 7 weeks, after which they were refed for 3 weeks with either CSB+ (n = 10), CSB++ (n = 10) or CSB+/wp (n = 10). For reference, a fourth group continued on the maize diet (REF, n = 10). RESULTS: Following induction of undernutrition, body weight and length were 29±5% and 67±4% (means±SD) of values in age-matched pigs fed a nutritionally adequate diet, and the mean serum P level was 1.77±0.34 mmol/l. During the first week of refeeding, P levels in the CSB+ pigs decreased to 55% of values before refeeding (P < 0.05) while values in the CSB++ and CSB+/wp pigs were able to maintain their plasma phosphate at a similar level as before refeeding. CONCLUSION: We conclude that fortification of CSB with only monocalcium-phosphate does not prevent hypophosphatemia. Dairy products like skim milk powder or whey permeate may represent relevant sources of phosphorus during refeeding. The content and form of phosphorus in such diets need to be carefully evaluated, and the undernourished piglet may be used to test the efficacy of such diets.

Serum phosphate and magnesium in children recovering from severe acute undernutrition in Ethiopia: an observational study.

BACKGROUND: Children with severe acute malnutrition (SAM) have increased requirements for phosphorus and magnesium during recovery. If requirements are not met, the children may develop refeeding hypophosphatemia and hypomagnesemia. However, little is known about the effect of current therapeutic diets (F-75 and F-100) on serum phosphate (S-phosphate) and magnesium (S-magnesium) in children with SAM. METHODS: Prospective observational study, with measurements of S-phosphate and S-magnesium at admission, prior to rehabilitation phase and at discharge in children aged 6-59 months admitted with SAM to Jimma Hospital, Ethiopia. Due to shortage of F-75, 25 (35 %) children were stabilized with diluted F-100 (75 kcal/100 ml). RESULTS: Of 72 children enrolled, the mean age was 32 ± 14 months, and edema was present in 50 (69 %). At admission, mean S-phosphate was 0.92 ± 0.34 mmol/L, which was low compared to normal values, but increased to 1.38 ± 0.28 mmol/L at discharge, after on average 16 days. Mean S-magnesium, at admission, was 0.95 ± 0.23 mmol/L, and increased to 1.13 ± 0.17 mmol/L at discharge. At discharge, 18 (51 %) children had S-phosphate below the normal range, and 3 (9 %) had S-phosphate above. Most children (83 %) had S-magnesium above normal range for children. Both S-phosphate and S-magnesium at admission were positively associated with serum albumin (S-albumin), but not with anthropometric characteristics or co-diagnoses. Using diluted F-100 for stabilization was not associated with lower S-phosphate or S-magnesium. CONCLUSION: Hypophosphatemia was common among children with SAM at admission, and still subnormal in about half of the children at discharge. This could be problematic for further recovery as phosphorus is needed for catch-up growth and local diets are likely to be low in bioavailable phosphorus. The high S-magnesium levels at discharge does not support that magnesium should be a limiting nutrient for growth in the F-100 diet. Although diluted F-100 (75 kcal/100 mL) is not designed for stabilizing children with SAM, it did not seem to cause lower S-phosphate than in children fed F-75.

Undernourished Children and Milk Lactose.

BACKGROUND: Lactose is an important energy source in young mammals, and in fully breast-fed human infants, it constitutes around 40% of the total daily energy intake. The role of lactose in feeding of undernourished infants and young children is not well described. OBJECTIVE: A narrative review of the potential positive and negative effects of lactose in the treatment of undernourished children. METHODS: Searches were conducted using PUBMED and Web of Science up to July 2015. Relevant references in the retrieved articles were included. RESULTS: Lactose may exhibit several health benefits in young children, including a prebiotic effect on the gut microbiota and a positive effect on mineral absorption. Studies in piglets suggest there might also be a stimulating effect on growth, relative to other carbohydrates. Lactose intolerance is a potential concern for undernourished children. Most undernourished children seem to tolerate the currently recommended (low lactose level) therapeutic foods well. However, a subgroup of severely undernourished children with secondary lactase deficiency due to severe diarrhea or severe enteropathy may benefit from products with even more restricted lactose content. At limited extra costs, lactose or lactose-containing milk ingredients may have beneficial effects if added to food products for undernourished children. CONCLUSIONS: Lactose may be an overlooked beneficial nutrient for young and undernourished children. Research is needed to define the balance between beneficial and detrimental effects of lactose in undernourished children at different ages and with different degrees of diarrhea and intestinal integrity.

Changes in plasma phosphate during in-patient treatment of children with severe acute malnutrition: an observational study in Uganda.

BACKGROUND: Children treated for severe acute malnutrition (SAM) are at risk of refeeding hypophosphatemia. Therapeutic diets have only recently become fortified with phosphorus to meet United Nations (UN) specifications, but to our knowledge no studies have investigated the effect. OBJECTIVE: The aim was to assess concentrations and correlates of plasma phosphate (P-phosphate) at admission and during treatment and to identify correlates of changes in P-phosphate. DESIGN: This was a prospective observational study in 6- to 59-mo-old children admitted for treatment of SAM to Mulago Hospital, Uganda. P-phosphate was measured at admission, on the second day of treatment with a therapeutic formula containing 75 kcal/100 mL and 560 mg phosphorus/L (F-75, Nutriset), at the start of the transition to a therapeutic formula containing 100 kcal/100 mL and 579 mg phosphorus/L (F-100; Nutriset), at day 2 of transition, and at discharge. RESULTS: Among 120 children, mean ± SD P-phosphate at admission was 1.04 ± 0.31 mmol/L and increased by 0.43 (95% CI: 0.35, 0.52) mmol/L during the first 2 d and more slowly toward discharge. Most (79%) children experienced their lowest P-phosphate concentration at admission, and none developed severe hypophosphatemia. P-phosphate was lowest in children with edema and with elevated C-reactive protein, and a lower increase was seen with increasing caretaker-reported severity of illness. Partially or fully replacing F-75 with rice porridge (i.e., a local practice to reduce diarrhea) during the first 2 d of stabilization was associated with a 0.34-mmol/L (95% CI: 0.18, 0.50 mmol/L) lower increase in P-phosphate during the same first 2 d. CONCLUSIONS: F-75, which complies with UN specifications and provides 73 mg phosphorus · kg(-1) · d(-1) (130 mL · kg(-1) · d(-1)), seems to prevent refeeding hypophosphatemia in children with SAM. Replacing this formula with rice porridge during the first days of treatment to manage diarrhea may have an adverse effect on P-phosphate concentrations. This study was registered at http://www.isrctn.com as ISRCTN55092738.

Cardiac Dysfunction in a Porcine Model of Pediatric Malnutrition.

BACKGROUND: Half a million children die annually of severe acute malnutrition and cardiac dysfunction may contribute to the mortality. However, cardiac function remains poorly examined in cases of severe acute malnutrition. OBJECTIVE: To determine malnutrition-induced echocardiographic disturbances and longitudinal changes in plasma pro-atrial natriuretic peptide and cardiac troponin-T in a pediatric porcine model. METHODS AND RESULTS: Five-week old piglets (Duroc-x-Danish Landrace-x-Yorkshire) were fed a nutritionally inadequate maize-flour diet to induce malnutrition (MAIZE, n = 12) or a reference diet (AGE-REF, n = 12) for 7 weeks. Outcomes were compared to a weight-matched reference group (WEIGHT-REF, n = 8). Pro-atrial natriuretic peptide and cardiac troponin-T were measured weekly. Plasma pro-atrial natriuretic peptide decreased in both MAIZE and AGE-REF during the first 3 weeks but increased markedly in MAIZE relative to AGE-REF during week 5-7 (p ≤ 0.001). There was overall no difference in plasma cardiac troponin-T between groups. However, further analysis revealed that release of cardiac troponin-T in plasma was more frequent in AGE-REF compared with MAIZE (OR: 4.8; 95%CI: 1.2-19.7; p = 0.03). However, when release occurred, cardiac troponin-T concentration was 6.9-fold higher (95%CI: 3.0-15.9; p < 0.001) in MAIZE compared to AGE-REF. At week 7, the mean body weight in MAIZE was lower than AGE-REF (8.3 vs 32.4 kg, p < 0.001), whereas heart-weight relative to body-weight was similar across the three groups. The myocardial performance index was 86% higher in MAIZE vs AGE-REF (p < 0.001) and 27% higher in MAIZE vs WEIGHT-REF (p = 0.025). CONCLUSIONS: Malnutrition associates with cardiac dysfunction in a pediatric porcine model by increased myocardial performance index and pro-atrial natriuretic peptide and it associates with cardiac injury by elevated cardiac troponin-T. Clinical studies are needed to see if the same applies for children suffering from malnutrition.

Inclusion of Small Indigenous Fish Improves Nutritional Quality During the First 1000 Days.

BACKGROUND: Within food-based approaches to improve nutrition during the first 1000 days of life, improved formulations of food products and the use of animal source foods, such as fish, are 2 widely cited strategies; however, there are few examples where the 2 strategies are combined. Furthermore, although small indigenous fish are highly nutritious and available to the poor in many regions of the world, their importance is often overlooked. OBJECTIVE: To document the development of 2 nutritious fish-based food products in Bangladesh: a chutney for pregnant and lactating women (PLW) and a complementary food (CF) for infants and young children (6-23 months), including potential contributions to recommended or desirable nutrient intakes in the first 1000 days, processing methods, and nutrient composition. METHODS: Local nutrient-rich ingredients and simple processing methods based on traditional knowledge (for the chutney), and a literature review (for the CF), were selected and trial batches produced. Products were analyzed for nutrient composition using standard analytical procedures and results compared with recommended or desirable nutrient intakes for women and children. RESULTS: Both products could contribute significantly to micronutrient intakes of PLW (24% of iron and 35% of calcium recommended intakes) and macro- and micronutrient intake of infants and young children (≥ 65% of vitamin A, ≥ 61% of zinc, and 41% of iron desirable intakes) when consumed in the proposed serving size. CONCLUSION: Inclusion of small indigenous fish as an underutilized animal source food in combination with other local nutrient-rich ingredients in food products represents a promising food-based strategy to improve nutrition, with many additional potential benefits for communities involved in production, and therefore warrants further investigation.

Predictors of oedema among children hospitalized with severe acute malnutrition in Jimma University Hospital, Ethiopia: a cross sectional study.

BACKGROUND: Severe acute malnutrition has two main clinical manifestations, i.e., oedematous and non-oedematous. However, factors associated with oedema are not well established. METHODS: Children 0.5-14 years of age with SAM (MUAC < 11.0 cm or weight-for-height < 70 % of median and/or nutritional oedema) admitted to the nutrition unit were included. Information on infections before and during admission was collected together with anthropometry. Predictors of oedema was analysed separately for younger (< 60 months) and older children (≥ 60 months). RESULTS: 351 children were recruited (median age: 36 months (interquartile range 24 to 60); 43.3% females). Oedema was detected in 61.1%. The prevalence of oedema increased with age, peaked at 37-59 months (75%) and declined thereafter. Infection was more common in the younger group (33% vs. 8.9%, p < 0.001) and in this group children with oedema had less infections (25.2% vs. 45.1%, p = 0.001). In the older group the prevalence of infections was not different between oedematous and non-oedematous children (5.5% v. 14.3%, p = 0.17). In the younger group oedema was less common in children with TB (OR = 0.20, 95% CI: 0.06, 0.70) or diarrhea (OR = 0.40, 95% CI: 0.21, 0.73). CONCLUSIONS: The proportion of oedema in SAM peaked at three to five years of age and a considerable proportion was above 5 years. Furthermore, the prevalence of infection seemed to be lower among children with oedema. Further studies are needed to better understand the role of infection-immunity interaction.

Malnutrition induces gut atrophy and increases hepatic fat infiltration: studies in a pig model of childhood malnutrition.

Childhood malnutrition is a problem in developing countries, and pathological changes in digestive organs such as the intestine and liver are poorly understood. An animal model to study the progression of severe acute malnutrition could elucidate pathological changes in the intestine and liver. We sought to characterize growth and clinical changes during malnutrition related to structural and functional indices in the intestine and liver. Newly weaned piglets were given ad libitum access to a maize flour diet (MAIZE, n=9) or a nutritionally optimized reference diet (REFERENCE, n=12) for 7 weeks. Growth, hematology and clinical biochemistry where recorded weekly. After 7 weeks, the MAIZE pigs had lower body weights than the REF pigs (8.3 kg vs. 32.4 kg, P < 0.001), indicating severe stunting and moderate to severe wasting. This was paralleled by lower values for hematocrit, hemoglobin and mean cell volume in MAIZE vs. REFERENCE (P < 0.01), indicating anemia. Although the observed temporal changes in MAIZE were associated with atrophy of the small intestinal mucosa (P < 0.001), digestive enzyme activity was only marginally reduced. Serum alanine aminotransferase, bilirubin and albumin were increased in the MAIZE pigs (P < 0.001), and the liver had a vacuolated appearance and tendency toward increased triglyceride content (P=0.054). We conclude that liver and intestinal indices are compromised during malnutrition and are associated with temporal changes in growth and hematological and biochemical endpoints. The pig model is relevant for malnourished infants and can act as a valuable tool for understanding the pathophysiology of malnutrition.

Body composition from birth to 6 mo of age in Ethiopian infants: reference data obtained by air-displacement plethysmography.

BACKGROUND: Data on body composition in infancy may improve the understanding of the relation between variability in fetal and infant growth and disease risk through the life course. Although new assessment techniques have recently become available, body composition is rarely described in infants from low-income settings. OBJECTIVE: The aim of this study was to provide reference data for fat mass (FM) and fat-free mass (FFM) from birth to the age of 6 mo from an urban African population. DESIGN: We conducted a prospective cohort study among infants from Jimma, Ethiopia. FM and FFM were measured at birth and at 1.5, 2.5, 3.5, 4.5, and 6 mo of age with air-displacement plethysmography (ADP) validated against a stable isotope method in a subsample. Reference charts and reference tables with z scores and percentiles for FM, FFM, FM index (FMI; in kg/m(2)), and FFM index (FFMI: in kg/m(2)) were constructed with the lambda-mu-sigma method. RESULTS: Body composition growth charts were based on a total of 2026 measurements of body composition obtained from 378 infants. FM and FMI gain progressed in a logarithmic-shaped curve and variation increased with increasing age, whereas FFM increased in an almost linear manner with a minor deceleration at around 3 mo of age. The FFMI curve showed a very modest exponential increase with age. CONCLUSIONS: By presenting z scores and centile reference charts for an apparently healthy urban Ethiopian infant population, this study represents a first step toward providing reference data on FM and FFM for an urban African context, which is important for future clinical care and research. This study was registered at www.controlled-trials.com as ISRCTN46718296.