Hypoallergenic and anti-inflammatory feeds in children with complicated severe acute malnutrition: an open randomised controlled 3-arm intervention trial in Malawi

Abstract

Intestinal pathology in children with complicated severe acute malnutrition (SAM) persists despite standard management. Given the similarity with intestinal pathology in non-IgE mediated gastrointestinal food allergy and Crohn's disease, we tested whether therapeutic feeds effective in treating these conditions may benefit children with complicated SAM. After initial clinical stabilisation, 95 children aged 6-23 months admitted at Queen Elizabeth Central Hospital, Blantyre, Malawi between January 1^st and December 31^st, 2016 were allocated randomly to either standard feeds, an elemental feed or a polymeric feed for 14 days. Change in faecal calprotectin as a marker of intestinal inflammation and the primary outcome was similar in each arm: elemental vs. standard 4.1 μg/mg stool/day (95% CI, -29.9, 38.15; P = 0.81) and polymeric vs. standard 10 (-23.96, 43.91; P = 0.56). Biomarkers of intestinal and systemic inflammation and mucosal integrity were highly abnormal in most children at baseline and abnormal values persisted in all three arms. The enteropathy in complicated SAM did not respond to either standard feeds or alternative therapeutic feeds administered for up to 14 days. A better understanding of the pathogenesis of the gut pathology in complicated SAM is an urgent priority to inform the development of improved therapeutic interventions.

Figure 1

Flowchart. Study flow diagram of children with severe acute malnutrition assessed for eligibility and recruited for the study. ¹Two additional children were known to have died after the 14-day study period and are not included in the Figure.

Figure 2

Biomarkers according to intervention arm. Box plots show values at baseline (or up to day 3) and day 14 (±3 days) according to intervention group (standard: blue, elemental: red, polymeric: green). Boxplots summarise the median (midline), the mean (diamond marker) and interquartile ranges (upper and lower box). Whiskers are drawn to the nearest value within 1.5 times the IQR. Values outside of this range are shown as circles. Light blue shading shows normal range.

Figure 3

Anthropometry according to intervention arm. Box plots show parameter at baseline (or up to day 3) and day 14 (±3 days) according to intervention group (standard: blue, elemental: red, polymeric: green) and show the median (midline), the mean (diamond marker) and interquartile ranges (upper and lower box). Whiskers are drawn to the nearest value within 1.5 times the IQR. Values outside of this range are shown as circles.