Slow Introduction of Nutrition for Ill Malnourished Children

The goal of this clinical trial is to learn if giving lower calorie feeds during the first stage of treatment helps improve survival in severely malnourished children who are ill. The main question it aims to answer is: Is it safe to feed ill severely malnourished children lower calorie feeds during the early treatment phase? Researchers will compare two lower calorie feeds (F50 and F35) to the standard feed (F75) to see if they help children recover safely without increasing their risk of low blood sugar (hypoglycemia). Participants will: * Receive one of the lower calorie feeds (F50 or F35) or the standard feed (F75) during their hospital stay. * Be closely monitored for low blood sugar and signs for worsening of clinical symptoms. * Be treated until they are stable and ready to be fed more calories to help them gain weight.

Malnutrition is a leading cause of death, contributing to nearly 45% of all deaths in children under the age of 5 years worldwide. In its most severe form, severe malnutrition remains prevalent globally affecting more than 45 million children. Severely malnourished children have a strongly increased risk of death from common infectious diseases. Updates in treatment protocols for severe malnutrition have been the most impactful intervention against childhood mortality. Management of severely malnourished children hospitalized with critical illness is based on guidelines developed by the World Health Organization and consists of three main components: 1. Clinical stabilization 2. Treatment of underlying infections 3. Nutritional rehabilitation. Clinical stabilization includes administration of broad-spectrum antibiotics, fluid resuscitation (if needed) and providing a nutritional stabilization feed that is called 'F75'. F75 was designed in the 1990's assuming that severely malnourished children with infections are metabolically vulnerable and have a range of micronutrient disturbances. F75 aims to provide 95 kcal/kg/day and was not intended for weight gain since, during this initial period, children are actively fighting infections. Once clinically stabilized, on average after 3-5 days, children are transitioned from F75 to ready-to-use therapeutic foods (RUTF) that provide a substantially higher amount of protein and calories to promote rapid weight gain. Some children fail this transition and have to revert back to F75 for a period of time due to clinical deterioration or not tolerating the RUTF. Despite protocolized management of these highly vulnerable patients, mortality rates have remained high over the past decades and reported to range between 10-30%, depending on population, setting and duration of follow up. Scientific evidence from the last decade has started to reform the approach to care for critically ill children in relation to feeding. Evidence shows that, during severe infection, the body enters a catabolic state, which is critical for immune function and pathogen clearance. Overfeeding during this phase may disrupt essential metabolic processes, including a process of cellular recycling called autophagy, which play a key role in fighting infections. Studies in both high- and low-resource settings have shown that limiting caloric intake in the early days of critical illness may improve clinical outcomes, including reducing the risk of infections and decreasing ICU stay durations. No clinical trial has examined the optimal caloric intake for ill severely malnourished children in LMIC and the current F75 composition was only based on expert opinion. Our population and treatment settings are substantially different compared to high income settings. Children in LMIC are often wasted to a degree of severity not frequently observed in high resource settings. Severely malnourished children are thought to be at risk of refeeding syndro Покажи пълното описание...

Inclusion Criteria: * Age - greater than or equal to 6 months to less than 59 months (age range for which WHO guidelines were developed and where children are not expected to be exclusively breastfeeding * Admitted to hospital with acute, non-traumatic illness and having received a maximum of 2 feeds of F75 at time of enrolment * Severe malnutrition (WHZ \<-3 z-scores of the median WHO growth standards and/or MUAC \<115mm) * Accompanied by care provider able to provide written or witnessed informed consent * Primary caregiver plans to stay in the study area for the duration of the study * Having no more than one clinical sign displayed below "Clinical/Lab Feature \& Criteria" Exclusion Criteria: * Has oedematous malnutrition (excluded for this safety focused trial as fluid accumulation influences weight which is used to calculate required caloric intake) * Requires immediate cardiac/respiratory resuscitation (chest compressions/ventilation) * Clinical contraindications for enteral nutrition * Admission for traumatic or surgical indication * Weighs \<3.5kg * Presence of terminal illness likely to result in death within 6 months * Known congenital heart disease * Have had 2 documented hypoglycaemic events in hospital * More than one clinical sign displayed below "Clinical/Lab Feature \& Criteria" * Primary caregiver declines to provide informed consent Clinical/Lab Feature \& Criteria Guidelines Clinical/Lab Feature: Respiratory distress Oxygenation Criteria: "Subcostal in-drawing" or "nasal flaring" or "head-nodding" Clinical/Lab Feature: Oxygenation Criteria: "Central cyanosis" or SaO2 \<90% Clinical/Lab Feature: Circulation Criteria: Limb temperature gradient or capillary refill \>3 seconds Clinical/Lab Feature: Reduced conscious level Criteria: AVPU \< "A" Clinical/Lab Feature: Rapid pulse Criteria: Heartbeat per min \> 180 Clinical/Lab Feature: Severe anemia Criteria: Haemoglobin \< 7g/dl Clinical/Lab Feature: Hypoglycemia Criteria: Blood glucose \< 3mmol/L Clinical/Lab Feature: Abnormal temperature Criteria: Axial temperature \<36 or \>38oC Clinical/Lab Feature: Very low MUAC Criteria: MUAC \<11cm