OptiDiag: Biomedical Investigations for Optimized Diagnosis and Monitoring of Severe Acute Malnutrition (SAM): Elucidating the Heterogeneous Diagnosis of SAM by Current Anthropometric Criteria and Moving Beyond
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 473
- 试验地点
- 3
- 主要终点
- Stable Isotope Analysis (SIA)
研究概览
简要总结
INTRODUCTION
In 2014, 50 million children under 5 suffered from acute malnutrition, of which 16 million suffered from SAM, most of them living in sub-Saharan Africa and Southeast Asia. SAM children have higher risk of mortality (relative risk between 5 and 20). It is an underlying factor in over 50% of the 10 - 11 million preventable deaths per year among children under five. At present, 65 countries have implemented WHO recommendations for SAM treatment (both in-patient for complicated cases and outpatient for uncomplicated cases) but these programs have very low coverage, reaching only around 10 - 15 % of SAM children.
In 2009 the World Health Organization (WHO) and the United Nations Children's Fund (UNICEF) issued a joint statement in an effort to harmonize the application of anthropometric criteria for SAM diagnosis and monitoring in child aged 6 - 59 months; the statement presents recommended cut-offs, and summarizes the rational for the adoption, of the following two anthropometric criteria:
- Weight-for-Height Z-Score (WHZ): "WHO and UNICEF recommend the use of a cut-off for weight-for-height of below -3 standard deviations (SD) of the WHO standards to identify infants and children as having SAM." Additionally, analysis of existing data show that children with a WHZ < -3 have a highly elevated risk of death.
- Mid-Upper Arm Circumference (MUAC): "WHO standards for the MUAC-for-age show that in a well-nourished population there are very few children aged 6 - 59 months with a MUAC less than 115 mm. Children with a MUAC less than 115 mm have a highly elevated risk of death compared to those who are above. Thus it is recommended to [use] the cut-off point [of] 115 mm to define SAM with MUAC."
GENERAL OBJECTIVE
To generate new evidence on pathophysiological process, nutritional needs and risks associated with different types of anthropometric deficits in children under 5, in order to optimize the diagnosis and treatment of SAM.
SPECIFIC OBJECTIVES
- To compare nutritional status, metabolism, pathophysiological process and risks in different types of SAM anthropometric diagnosis, with or without concomitant stunting (growth retardation).
- To analyze the extent to which current SAM treatment is promoting recovery and healthy growth in different categories of children.
- To evaluate the relevance of current discharge criteria used in nutrition programs and their association with metabolic recovery, in different age groups and among those who are stunted.
- To test novel rapid tests of emerging biomarkers predicting long-term outcomes and mortality risk in the field.
METHODOLOGY
A wide range of supplementary information related to nutritional status, body composition, metabolic and immune status, including emerging biomarkers of metabolic deprivation and vulnerability, will be collected besides anthropometry during prospective observational studies. They will be collected with minimum level of invasiveness, compatible with field work requirements in the humanitarian context.
Phase 1: Cross-sectional surveys. Phase 2: Prospective cohort studies involving SAM children between 6 months and 5 years old.
Children admitted as SAM at the nutrition centers will be enrolled into the cohort. The follow up duration will be at least three months.
EXPECTED OUTCOMES
- Confirmation of current hypotheses related to:
- possible misdiagnosis of SAM made by MUAC or WHZ criteria,
- varying degree of severity and need for admission to treatment of the different types of diagnosis,
- underlying heterogeneity of the pathophysiology.
- Generation of new algorithms for the assessment and classification of malnourished children, based on the combined use of emerging biomarkers and anthropometric measures, or on the modification of anthropometric criteria.
- Generation of new treatment paradigms based on the predictive value of biomarkers in combination with traditional anthropometric measures. This will enable us to assess the power of current treatment regimens to promote long-term weight gain and growth and will allow us to tailor treatment to the physiological needs of the child.
详细描述
DIAGNOSTIC DISCREPANCY
According to WHO experts, WHZ and MUAC can be used independently to indicate severe acute malnutrition (WH. There is however a significant and sometimes huge discrepancy between these two criteria: they do not usually identify the same children as acutely malnourished; moreover when used as proxy indicator to assess a deteriorating nutritional situation at a population level, these criteria do not report the same level of global acute malnutrition in the same zone.
It was reported that only about 40% of SAM cases identified by one indicator are also diagnosed as such by the other. For example, among severely malnourished children hospitalized in rural Kenya, 65.1% (486/746) of the WHZ -3 cases also had a MUAC < 115 mm, whereas 56% (489/873) of the MUAC < 115 mm cases were also identified by WHZ < -3. In that study, 42.9% (489/1140) of the SAM cases were identified by both indicators. The discrepancy between the two indicators can be even more extreme.
Fernandez et al. reported that among 34,937 children between the ages of 6 - 59 months from 39 nutritional surveys, 75% of the children with a WHZ < -3 were not identified by a MUAC < 115 mm. In Cambodia, this proportion was above 90%, whereas 80% of MUAC < 115 mm were not detected by WHZ < - 3.
Most of the time, caseloads defined by WHZ are much larger than by MUAC, but the contrary may happen as well, especially in the younger age groups.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 6 Months 至 5 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosed SAM and eligible for CMAM treatment, defined as: (1) WHZ < -3 and/or MUAC < 115 mm; (2) No bilateral pitting edema; (3) Children without the general danger signs of illness as per the Integrated Management of Childhood Illness (IMCI) guidelines like lethargy, unconsciousness, convulsions or severe vomiting (WHO 2005).
- •Resident of the catchment area at the time of inclusion; and
- •Caretakers consent for the child to participate.
排除标准
- •Plans to leave the catchment area within the next 6 months;
- •Known peanut and/or milk allergy;
- •Admitted for SAM treatment within the past 6 months prior to recruitment (including re-admission after default, relapse or medical transfer);
- •Malformations which may affect food intake such as cleft palate, cerebral palsy, Down's syndrome; and,
- •The presence of general danger signs as per the IMCI guidelines.
结局指标
主要结局
Stable Isotope Analysis (SIA)
时间窗: At admission
Describe and compare the different types of SAM anthropometric diagnoses based on Stable Isotope Analysis (SIA)
Clinical Signs
时间窗: At admission
Describe and compare the different types of SAM anthropometric diagnoses based on the severity of clinical signs at admission; these include: dehydration, visible signs of wasting, pulse, signs of micronutrient deficiency, acute resipiratory infections, respiratory rate, temperature, dermatosis and hair changes and diarrhea.
Micronutrient status
时间窗: At admission
Describe and compare the different types of SAM anthropometric diagnoses based on micronutrient status.
Leptin
时间窗: At admission
Describe and compare the different types of SAM anthropometric diagnoses based on circulating leptin.
Bioelectric impedance (BI)
时间窗: At admission
Describe and compare the different types of SAM anthropometric diagnoses based on bioelectric impedance (BI).
Patient's health and nutritional status (caretaker's perception)
时间窗: At admission
Describe and compare the different types of SAM anthropometric diagnoses based on the caretaker's perception of the patient's health and nutritional status.
次要结局
- Clinical signs: pulse(At 2 weeks & 8 weeks after admission.)
- Clinical signs: temperature(At 2 weeks & 8 weeks after admission.)
- Patient's health and nutritional status (caretaker's perception)(At 2 weeks & 8 weeks after admission.)
- Clinical signs: visible wasting(At 2 weeks & 8 weeks after admission.)
- Clinical signs: dehydration(At 2 weeks & 8 weeks after admission.)
- Stable Isotope Analysis (SIA)(At 2 weeks, 4 weeks, 6 weeks & 8 after admission.)
- Clinical signs: acute respiratory infection(At 2 weeks & 8 weeks after admission.)
- Clinical signs: respiratory rate(At 2 weeks & 8 weeks after admission.)
- Bioelectric impedance (BI)(At 2 weeks & 8 weeks after admission.)
- Clinical signs: micronutrient deficiency(At 2 weeks & 8 weeks after admission.)
- Clinical signs: dermatosis(At 2 weeks & 8 weeks after admission.)
- Clinical signs: hair changes(At 2 weeks & 8 weeks after admission.)
- Micronutrient status(At 2 weeks & 8 weeks after admission.)
- Clinical signs: diarrhea(At 2 weeks & 8 weeks after admission.)
- Early weight gain(After 2 weeks and 4 weeks after admission.)
- Leptin(At 2 weeks & 8 weeks after admission.)
- Treatment outcomes(Events occuring up to maximum treatment duration as per national protocol (up to 12 weeks in Bangladesh, up to 16 weeks in Burkina Faso, and up to 12 weeks in Liberia).)