Project 452092

Malnutrition is related to 45% of all childhood deaths globally. Children with malnutrition generally do not die from malnutrition directly, but malnutrition makes them vulnerable for common infectious illnesses such as lung and gut infection. Managing these ill severely malnourished children is especially challenging. The World Health Organization (WHO) developed guidelines on how to manage hospitalized children with severe malnutrition but despite following guidelines mortality rates have remained up to 30%. The WHO guidelines include standardized feeding using a liquid product called F75. Evidence from very ill children admitted to intensive care units has indicated that overfeeding these children is harmful and should be avoided. Our group recently demonstrated that the current F75 formulation carries a significant risk of overfeeding ill severely malnourished children. We therefore propose to perform an intervention trial where we will test different forms of F75 providing lower amounts of calories. As these children are at risk of developing low blood sugars, which could be increased when given lower calories, we first need to determine the optimal amount of calories in terms of safety. We will carry out this safety trial in a leading hospital in Malawi with experience in clinical trials in children. We will assign individual children to one of three F75 formulations. Our main outcome is risk of developing low blood sugars which we will measure continuously. This will allow us to carry out this trial in the safest way possible. Once we have the determined the optimal calories that can be given in terms of safety, we would then be in a position to perform a large intervention trial whereby we randomly give children the standard F75 or a reduced calorie feeds and test the effect on mortality. This work has the potential to radically change how we manage seriously ill severely managed children and reduce the mortality in the most vulnerable children globally.