Effectiveness of three commonly used transition phase diets in the inpatient management of children with severe acute malnutrition: a pilot randomized controlled trial in Malawi.

BACKGROUND: The case fatality rate of severely malnourished children during inpatient treatment is high and mortality is often associated with diarrhea. As intestinal carbohydrate absorption is impaired in severe acute malnutrition (SAM), differences in dietary formulations during nutritional rehabilitation could lead to the development of osmotic diarrhea and subsequently hypovolemia and death. We compared three dietary strategies commonly used during the transition of severely malnourished children to higher caloric feeds, i.e., F100 milk (F100), Ready-to-Use Therapeutic Food (RUTF) and RUTF supplemented with F75 milk (RUTF + F75). METHODS: In this open-label pilot randomized controlled trial, 74 Malawian children with SAM aged 6-60 months, were assigned to either F100, RUTF or RUTF + F75. Our primary endpoint was the presence of low fecal pH (pH ≤ 5.5) measured in stool collected 3 days after the transition phase diets were introduced. Secondary outcomes were duration of hospital stay, diarrhea and other clinical outcomes. Chi-square test, two-way analysis of variance and logistic regression were conducted and, when appropriate, age, sex and initial weight for height Z-scores were included as covariates. RESULTS: The proportion of children with acidic stool (pH ≤5.5) did not significantly differ between groups before discharge with 30, 33 and 23% for F100, RUTF and RUTF + F75, respectively. Mean duration of stay after transitioning was 7.0 days (SD 3.4) with no differences between the three feeding strategies. Diarrhea was present upon admission in 33% of patients and was significantly higher (48%) during the transition phase (p < 0.05). There was no significant difference in mortality (n = 6) between diets during the transition phase nor were there any differences in other secondary outcomes. CONCLUSIONS: This pilot trial does not demonstrate that a particular transition phase diet is significantly better or worse since biochemical and clinical outcomes in children with SAM did not differ. However, larger and more tightly controlled efficacy studies are needed to confirm these findings. TRIAL REGISTRATION: ISRCTN13916953 Registered: 14 January 2013.

Impaired glucose absorption in children with severe malnutrition.

OBJECTIVE: To quantify intestinal glucose absorption in children with two types of severe malnutrition, kwashiorkor and marasmus, compared with healthy children. STUDY DESIGN: Children with kwashiorkor (n = 6) and marasmus (n = 9) and control subjects (n = 3) received a primed (13 mg/kg), constant infusion (0.15 mg/kg/min) of [6,6H2]glucose for 4.5 hours. Two hours after start of the infusion an oral bolus of glucose 1.75 g/kg labeled with [U-13C]glucose 10 mg/g was given and was followed by periodic blood sampling. Mathematical modeling was applied to determine oral glucose absorption. RESULTS: Median total glucose absorption was 5.9 mmol/kg, interquartile range (IQR) 4.5-6.7 mmol/kg and 4.4 (IQR 2.9-5.9) mmol/kg in children with kwashiorkor and marasmus compared with 7.7 (IQR 5.8-9.0) mmol/kg in control subjects; P = .03 compared with marasmus). Children with the lowest glucose absorption were found specifically in the kwashiorkor group and marasmic children with hypoalbuminemia. Severe impairment in absorption correlated with urinary 8-hydroxydeoxyguanosine secretion (r = -0.62, P = .01). CONCLUSIONS: Severe malnutrition is associated with an impaired glucose absorption and decreased glucose absorption correlates with oxidative stress in these children.

Mechanisms behind decreased endogenous glucose production in malnourished children.

Severe malnutrition is a major health problem in developing countries and can present itself as kwashiorkor or marasmus. Although marasmus is characterized by clinical wasting, kwashiorkor is associated with peripheral edema, oxidative stress, hypoalbuminemia, and hypoglycemia. The etiology of the hypoglycemia is poorly understood. We determined endogenous glucose production (EGP) in children with severe malnutrition. Children with kwashiorkor, marasmus, and controls received a primed constant infusion of [6,6H2]glucose for 2 h. An i.v. bolus of 13C-ketoisocaproic acid (KIC) was given, and breath samples were obtained during 2 h. Isotope dilution was used to calculate EGP, and 13CO2/12CO2 production was determined. Mean EGP ± SEM was 5.5 ± 0.3 mg/kg/min in the kwashiorkor group and 6.9 ± 0.4 mg/kg/min and 7.6 ± 0.7 mg/kg/min in the marasmic and control group, respectively, (p < 0.05 kwashiorkor versus marasmus and controls). EGP correlated with serum albumin concentration (r = 0.67; p < 0.001) and urinary 8-hydroxydeoxyguanosine as a marker of oxidative stress (r = -0.62; p < 0.005). 13CO2 secretion as a marker of hepatic mitochondrial function was significantly higher in the marasmic group compared with kwashiorkor and controls. We conclude that decreased EGP in severely malnourished children is related to the degree of hypoalbuminemia and oxidative stress but is not associated with a clear defect in hepatic mitochondrial function.

Acceptability and practicality of pGALS in screening for rheumatic disease in Malawian children.

The pGALS (paediatric Gait, Arms, Legs, Spine) Musculoskeletal (MSK) screen is validated in English-speaking school-aged children and has been shown to be useful in acute paediatric practice in the UK. The aim of this study is to evaluate the practicality and acceptability of pGALS in children in an acute hospital setting in Malawi. School-aged inpatients and children presenting to the Queen Elizabeth Hospital Blantyre, Malawi, participated. Practicality (time taken, degree of completion) and patient/parent assessed acceptability (time take, discomfort) were assessed using a 'smiley face' visual analogue scale. Fifty-one children (median age 8 years) were assessed; 23 out of 51 (45%) in the emergency department and the remainder were inpatients. Most presentations were infection or trauma related (n = 35, 69%). Practicality of pGALS was good [median time to complete pGALS--4 min (range 1.8-7.4)] and completed in 48 out of 51 children (94%). Acceptability was high; 98% of parents considered the time taken to be acceptable, 84% of children deemed little/no additional discomfort. Abnormalities using pGALS were found in 21 out of 51 (41%), mostly in the lower limbs. The pGALS MSK screen was practical and acceptable in this acute setting. Abnormal findings were common.

Challenges in the Management of HIV-Infected Malnourished Children in Sub-Saharan Africa.

Infection with HIV, and oftentimes coinfection with TB, complicates the care of severely malnourished children in sub-Saharan Africa. These superimposed infections challenge clinicians faced with a population of malnourished children for whose care evidence-based guidelines have not kept up. Even as the care of HIV-uninfected malnourished children has improved dramatically with the advent of community-based care and even as there are hopeful signs that the HIV epidemic may be stabilizing or ameliorating, significant gaps remain in the care of malnourished children with HIV. Here we summarize what is currently known, what remains unknown, and what remains challenging about how to treat severely malnourished children with HIV and TB.

Kwashiorkor and marasmus are both associated with impaired glucose clearance related to pancreatic ß-cell dysfunction.

Severe malnutrition is a major health problem in developing countries and can present as kwashiorkor or marasmus. Kwashiorkor is associated with septicaemia, profound metabolic changes including hepatic steatosis, altered protein metabolism and increased oxidative stress. Limited data suggest that children with kwashiorkor have an impaired glucose tolerance and insulin secretion. Our objective was to determine glucose tolerance in children with kwashiorkor compared to marasmus and its relation to insulin secretion and sensitivity. Six children with kwashiorkor and 8 children with marasmus were studied. We were also able to include 3 healthy children for comparison. They received a primed (13 mg/kg), constant infusion (0.15 mg/kg/min) of [6,6-(2)H(2)]glucose for 4 h with serial blood sampling. In addition, an oral glucose tolerance test (OGTT) was performed with labeled 10 mg/g [U-(13)C]glucose. Glucose clearance was determined using mathematical modeling. Glucose clearance rates during the OGTT were -392 (range 309) mL/kg in children with kwashiorkor, -156 (426) mL/kg in marasmus and 279 (345) mL/kg in the control group. Glucose clearance rates correlated with plasma albumin concentrations (r=0.67, P=.001). Insulin responses were strongly impaired in both kwashiorkor and marasmus. There was no indication of peripheral or hepatic insulin resistance in the malnourished groups. We show that glucose clearance rates are affected in both children with marasmus as well as kwashiorkor, which correlate with plasma albumin concentrations. The disturbed glucose clearance in malnutrition is related to an impairment in insulin availability.