Dietary Rehabilitation in Severely Acutely Malnourished Children

Study Overview
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Brief Summary
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Severe acute malnutrition (SAM) is a life threatening condition and is defined by 1) a weight-for-height Z-score more than three standard deviations (SD) below the median based on the 2006 World Health Organization (WHO) growth standards, 2) a mid-upper arm circumference (MUAC) of less than 115 mm or 3) by the presence of nutritional edema. Signs such as edema, mucocutaneous changes, hepatomegaly, lethargy, anorexia, anemia, severe immune deficiency and rapid progression to mortality characterize a state commonly coined as complicated SAM. Kwashiorkor is one of the forms of complicated SAM commonly distinguished by the unmistakable presence of bipedal edema. SAM results in high mortality rates of up to half a million child deaths annually. Undernourished children are at higher risk of mortality ranging from three-times more risk among children with moderate malnutrition to 10-times in SAM children compared to well-nourished children. Children with complicated SAM require inpatient treatment in specialized centers. The Rehabilitation and Nutritional Education Center (CREN) is a specialized center in Burkina Faso receiving on average 10 SAM children per day. Recovery rate is lower than international standards; and adverse events and mortality remain strikingly high. The main objective of this study is to assess the underlying risk factors affecting the effectiveness of the nutritional therapeutic treatment protocol for complicated SAM children under 5 years of age who have been referred to the CREN, at the Centre Hôspitalier Universitaire Souro, Bobo Dioulasso, Burkina Faso. The specific objective of this study is to better understand underlying risk factors associated with a lower recovery rate and high mortality in complicated SAM children referred to CREN for inpatient care. Risk factors associated with poor response to a standard dietary treatment at any phase will be assessed retrospectively.

Detailed Description
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Severe acute malnutrition (SAM), defined as severe wasting [weight-to-height Z-score < -3 standard deviations (SD), based on the WHO Child Growth Standards] and / or the presence of nutritional edema, and / or mid-upper arm circumference (MUAC) <115 mm, is a condition that requires urgent attention and appropriate management to reduce mortality and promote recovery among children. Management of SAM children without complications is provided at the community level. Hospitalization in specialized care centers is necessary for SAM children with complications. SAM children with comorbidities have a greater risk of mortality and treatment failure. The knowledge of the specific adequate nutritional needs of SAM is limited. For the treatment of SAM in hospital, the WHO recommends the use of therapeutic milk low in protein 'F75' in the stabilization phase; and more protein-rich F100 or F75 combined with ready-to-use therapeutic foods (RUTF) in the transition phase. The WHO also recommends using as an alternative formula made of cereal flour, skimmed milk powder, oil, sugar, and a therapeutic vitamin and mineral complex (CMV), in case of shortage of the standard therapeutic milk F75 / F100 or in case of signs of intolerance (vomiting, diarrhea). The Refeeding Center - Centre de Récupération et d'Education Nutritionnelle (CREN) of the Sourô Sanou University Hospital Center (CHUSS) in Burkina Faso specializes in the care of SAM children with complications. In 2018, out of 500 children aged 6-59 months admitted for SAM with complications, the CHUSS CREN registered 86.8% full recovery, 8.2% dropout and 5% death. Although the recovery rate is higher than international standards (greater than 75%), the mortality rate remains higher than the recommended 3% by international standards; in addition to the challenges that are faced locally in maintaining high standards of care. At the CREN, the investigators and the nurses observed that some SAM children with complications can have severe diarrhea and vomiting after taking F75 (first phase of the nutritional treatment). It was also observed that other SAM children with edema, whose edema resolved in the first phase of treatment under F75, redeveloped edema when they received RUTF (Plumpy Nut®) in the transition phase according to the WHO 2013 protocol. This research project, which will be subdivided into a retrospective study and two prospective clinical trials aims to assess the risk factors affecting the response to dietary treatment in this center (the CREN, Burkina Faso) and to compare alternatives for treatment during the nutritional rehabilitation. The retrospective study assesses the factors of failure of dietary treatment in the three phases of nutritional rehabilitation to better understand underlying risk factors associated with a lower recovery rate and high mortality in complicated SAM children referred to CREN for inpatient care. Risk factors associated with poor response to a standard dietary treatment at any phase will be assessed retrospectively and include: Errors in the treatment (feeding) dosage that can be due to errors in anthropometric measurement and/or in reading the feeding regimen table by the CREN team; Low adherence of children to the therapeutic dietary regimen Comorbidities associated with malnutrition that can have an effect on the dietary treatment effectiveness Types of dietary regimen selected during the first phase of treatment [F75 vs. alternative F75 (cereal flour, oil, sugar, powdered milk) with OR without CMV)] and during the transition phase [F75 + RUTF ( Plumpy-Nut®), F100, alternative F75 (with and without CMV) + RUTF (Plumpy Nut®)]. The study will use data collected during admission and follow-up of SAM children with complications admitted at the CREN of the CHUSS from January 2014 to December 2018.

Official Title
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The Underlying Causes Affecting the Response to Dietary Rehabilitation in Severely Acutely Malnourished Children at the Center Hôspitalier Universitaire Sourô Sanou, Bobo Dioulasso, Burkina Faso

Conditions
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Severe Acute Malnutrition, Kwashiorkor, Nutritional Edema, Marasmus

Intervention / Treatment
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* Dietary Supplement: Standard F75
* Dietary Supplement: Alternative F75 With CMV
* Dietary Supplement: Alternative F75 Without CMV
* Dietary Supplement: F100
* Dietary Supplement: Standard F75 + RUTF
* Dietary Supplement: Alternative F75 with CMV + RUTF
* Dietary Supplement: Alternative F75 without CMV + RUTF


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Severe acute malnutrition defined as Weight-for-Height Z-score (WHZ) <- 3 SD AND / OR MUAC <115 mm AND / OR with edema With complications Who were admitted and treated in the refeeding center (CREN) of the CHUSS from January 2014 TO December 2018 Aged between 0 and 59 Months Exclusion Criteria: Older than 59 Months Moderate Acute Malnutrition (MAM)

Ages Eligible for Study
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Minimum Age: 0 Months
Maximum Age: 59 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Stabilization phase<br>The dietetic treatment is given by the nurses every 2 hours on the first day; then if tolerance is good, every 3 hours the following days. No family meals during the stabilization phase. But the baby can breastfeed. A child will receive an antibiotic as per the national protocol, malaria treatment if diagnosed with malaria, Vitamin A if symptomatic eye damage, Folic acid in case of anemia, antifungal in case of candidiasis. | Dietary Supplement: Standard F75<br>* F-75 contains 75 kcal and 0.9 g protein per 100 ml.<br>Dietary Supplement: Alternative F75 With CMV<br>* Cereal flour, oil, sugar, powdered milk with complex mineral-vitamin.<br>Dietary Supplement: Alternative F75 Without CMV<br>* Cereal flour, oil, sugar, powdered milk without complex mineral-vitamin.<br>|
| Transition phase<br>The child is assigned to one the therapeutic regimen depending on the treatment received during the stabilization phase and the results of the appetite test. | Dietary Supplement: F100<br>* 100 kcal and 3 g protein per 100 ml if the test of appetite at the end of the stabilization phase is negative (the child does not accept the Plumpynut)<br>Dietary Supplement: Standard F75 + RUTF<br>* Standard F75 with ready to-use therapeutic food (Plumpynut) if the test of appetite at the end of the stabilization phase is positive<br>Dietary Supplement: Alternative F75 with CMV + RUTF<br>* Alternative F75 + CMV with ready to-use therapeutic food (Plumpynut) if the test of appetite at the end of the stabilization phase is positive and the child received Alternative F75 + CMV during the stabilization phase<br>Dietary Supplement: Alternative F75 without CMV + RUTF<br>* Alternative F75 - CMV with ready to-use therapeutic food (Plumpynut) if the test of appetite at the end of the stabilization phase is positive and the child received Alternative F75 - CMV during the stabilization phase<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of days during the first phase of treatment | Average number of days spent in the stabilization phase in Days | Three to Seven days | 
| Number of days during the transition phase of treatment | Average number of days spent in the transition phase in Days | Three to Five days | 
| Daily weight gain during the first phase of treatment | Average daily weight gain in the stabilization phase in Grams | Three to Seven days | 
| Daily weight gain during the transition phase | Average daily weight gain in the transition phase in Grams | Three to Five days | 
| Edema redevelopment during the transition phase | Edema redevelopment during the transition phase after starting to resolve during the stabilizing phase. | Three to Five days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anorexia | Serious severe event that occurs at anytime during the treatment | Through study completion, an average of 15 days | 
| Mortality | Serious severe event that occurs at anytime during the treatment | Through study completion, an average of 15 days | 
| Diarrhea | Serious severe event that occurs at anytime during the treatment | Through study completion, an average of 15 days | 
| Vomiting | Serious severe event that occurs at anytime during the treatment | Through study completion, an average of 15 days | 
| Adherence to the dietary treatment | Daily intake of the administered dietary treatment | Through study completion, an average of 15 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Severe acute malnutrition, Nutritional rehabilitation, F75, F100, Ready to use therapeutic food (RUTF), Stabilization phase, Transition phase, Kwashiorkor, Marasmus