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      Childhood Acute Illness and Nutrition (CHAIN) Network: a protocol for a multi-site prospective cohort study to identify modifiable risk factors for mortality among acutely ill children in Africa and Asia

      protocol
      The Childhood Acute Illness and Nutrition Network
      BMJ Open
      BMJ Publishing Group
      acute illness, malnutrition, post-discharge, mortality, hospitalisation, resource-poor, child survival, children, infants

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          Abstract

          Introduction

          Children admitted to hospitals in resource-poor settings remain at risk of both inpatient and post-discharge mortality. While known risk factors such as young age and nutritional status can identify children at risk, they do not provide clear mechanistic targets for intervention. The Childhood Acute Illness and Nutrition (CHAIN) cohort study aims to characterise the biomedical and social risk factors for mortality in acutely ill children in hospitals and after discharge to identify targeted interventions to reduce mortality.

          Methods and analysis

          The CHAIN network is currently undertaking a multi-site, prospective, observational cohort study, enrolling children aged 1 week to 2 years at admission to hospitals at nine sites located in four African and two South Asian countries. The CHAIN Network supports the sites to provide care according to national and international guidelines. Enrolment is stratified by anthropometric status and children are followed throughout hospitalisation and for 6 months after discharge. Detailed clinical, demographic, anthropometric, laboratory and social exposures are assessed. Scheduled visits are conducted at 45, 90 and 180 days after discharge. Blood, stool and rectal swabs are collected at enrolment, hospital discharge and follow-up. The primary outcome is inpatient or post-discharge death. Secondary outcomes include readmission to hospital and nutritional status after discharge. Cohort analysis will identify modifiable risks, children with distinct phenotypes, relationships between factors and mechanisms underlying poor outcomes that may be targets for intervention. A nested case–control study examining infectious, immunological, metabolic, nutritional and other biological factors will be undertaken.

          Ethics and dissemination

          This study protocol was reviewed and approved primarily by the Oxford Tropical Research Ethics Committee, and the institutional review boards of all partner sites. The study is being externally monitored. Results will be published in open access peer-reviewed scientific journals and presented to academic and policy stakeholders.

          Trial registration number

          NCT03208725.

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          Most cited references22

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          Maternal and child undernutrition and overweight in low-income and middle-income countries

          The Lancet, 382(9890), 427-451
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            Evidence-based interventions for improvement of maternal and child nutrition: what can be done and at what cost?

            The Lancet, 382(9890), 452-477
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              Severe childhood malnutrition

              The main forms of childhood malnutrition occur predominantly in children <5 years of age living in low-income and middle-income countries and include stunting, wasting and kwashiorkor, of which severe wasting and kwashiorkor are commonly referred to as severe acute malnutrition. Here, we use the term ‘severe malnutrition’ to describe these conditions to better reflect the contributions of chronic poverty, poor living conditions with pervasive deficits in sanitation and hygiene, a high prevalence of infectious diseases and environmental insults, food insecurity, poor maternal and fetal nutritional status and suboptimal nutritional intake in infancy and early childhood. Children with severe malnutrition have an increased risk of serious illness and death, primarily from acute infectious diseases. International growth standards are used for the diagnosis of severe malnutrition and provide therapeutic end points. The early detection of severe wasting and kwashiorkor and outpatient therapy for these conditions using ready-to-use therapeutic foods form the cornerstone of modern therapy, and only a small percentage of children require inpatient care. However, the normalization of physiological and metabolic functions in children with malnutrition is challenging, and children remain at high risk of relapse and death. Further research is urgently needed to improve our understanding of the pathophysiology of severe malnutrition, especially the mechanisms causing kwashiorkor, and to develop new interventions for prevention and treatment.
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                Author and article information

                Journal
                BMJ Open
                BMJ Open
                bmjopen
                bmjopen
                BMJ Open
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                2044-6055
                2019
                5 May 2019
                : 9
                : 5
                : e028454
                Author notes
                [Correspondence to ] The Childhood Acute Illness and Nutrition Network; walson@ 123456uw.edu
                Article
                bmjopen-2018-028454
                10.1136/bmjopen-2018-028454
                6502050
                31061058
                ee2b4d6e-b277-49d4-8849-39b582f52ac2
                © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.

                This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

                History
                : 08 December 2018
                : 11 March 2019
                : 12 March 2019
                Funding
                Funded by: The Bill and Melinda Gates Foundation;
                Categories
                Paediatrics
                Protocol
                1506
                1719
                Custom metadata
                unlocked

                Medicine
                acute illness,malnutrition,post-discharge,mortality,hospitalisation,resource-poor,child survival,children,infants

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