Correlates of Gut Function in Children Hospitalized for Severe Acute Malnutrition, a Cross-sectional Study in Uganda.

OBJECTIVE: Children with severe acute malnutrition (SAM) may have impaired intestinal function, which can result in malabsorption, diarrhoea, and poor growth. This study evaluated the gut function of children with SAM using fecal and blood biomarkers and assessed their correlates. METHODS: A cross-sectional study, nested in a randomized trial (www.isrctn.com, ISRCTN 16454889), was conducted at Mulago hospital, Uganda among subgroups of 400 children with complicated SAM and 30 community controls. Gut function was evaluated by 5 biomarkers: plasma citrulline, fecal myeloperoxidase and fecal neopterin, bacterially derived 16S rRNA gene and internal transcribed Spacer region (ITS) specific for Candida spp. in blood. RESULTS: Compared with controls, children with SAM had lower median plasma citrulline (5.14 vs 27.4 µmol/L, P < 0.001), higher median fecal myeloperoxidase (18083 vs 7482 ng/mL, P = 0.001), and fecal neopterin (541 vs 210 nmol/L, P < 0.001). A higher blood concentration of 16S rRNA gene copy numbers was observed among children with SAM (95 vs 28 copies/µl, P = 0.05), whereas there was no difference in the blood concentration of Candida-specific ITS fragment.Among those with SAM, plasma citrulline was lower in children with edema, diarrhoea, dermatosis, and plasma C-reactive protein (CRP) >10 mg/L. Fecal neopterin was positively correlated with symptoms of fever and cough whereas it was negatively correlated with mid-upper arm circumference (MUAC), weight-for-height z score (WHZ), edema, and dermatosis. CONCLUSIONS: Children with complicated SAM seem to have impaired gut function characterized by reduced enterocyte mass, intestinal inflammation, and increased bacterial translocation.

Risk factors for death in children during inpatient treatment of severe acute malnutrition: a prospective cohort study.

BACKGROUND: Children who receive in-hospital treatment of severe acute malnutrition often have high mortality rates, and the reasons are not well understood. OBJECTIVE: We assessed risk factors for death in children who were treated for malnutrition in a hospital. DESIGN: In a prospective observational study of 120 children who were receiving in-hospital treatment of severe acute malnutrition in Uganda with therapeutic formulas F-75 and F-100, we collected data on symptoms, clinical findings, plasma markers of refeeding syndrome (electrolytes and phosphate), and acute phase reactants, and recorded the nutritional therapy given in hospital. RESULTS: Seventeen children (14%) died. Clinical risk factors for death were the presence of oral thrush (HR: 5.0; 95% CI: 1.6, 15.2), a caretaker-reported severity of illness on a visual analog scale (HR: 1.7; 95% CI: 1.1, 2.6), impaired consciousness (HR: 16.7; 95% CI: 3.1, 90.4), and a capillary refill time >2 s (HR: 3.9; 95% CI: 1.4, 11.3). HIV infection was not associated with mortality (HR: 3.0; 95% CI: 0.7, 12.4), which was most likely due to low power. Biochemical risk factors were a plasma C-reactive protein concentration >15 mg/L on admission and low plasma phosphate that was measured on day 2 (HR: 8.7; 95% CI: 2.5, 30.1), particularly in edematous children. The replacement of F-75 with unfortified rice porridge to ameliorate diarrhea was associated with a higher risk of death, particularly if given during the first 2 d (HR: 5.0; 95% CI: 1.9, 13.3), which was an association that remained after adjustment for potential confounders (HR: 69.5; 95% CI: 7.0, 694.6). CONCLUSIONS: Refeeding syndrome may occur in children who are treated for malnutrition, even with moderately low plasma phosphate, and, in particular, in children with edematous malnutrition. The replacement of F-75 with unfortified rice porridge is associated with increased risk of death, which is possibly mediated by lowering plasma phosphate. The identified clinical risk factors may potentially improve the triage of children with malnutrition. This trial was registered at www.isrctn.com as ISRCTN55092738.

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.