Child malnutrition& Adult NCDs-Generating Evidence on mechanistic links in Jamaica, Malawi & Ethiopia to inform future policy/practice (CHANGE study)

Lead Research Organisation: London Sch of Hygiene and Trop Medicine
Department Name: Epidemiology and Population Health

Abstract

Severe malnutrition in early childhood is a major public health concern globally. This has serious consequences:
- Short term: for children to survive: malnutrition in all its forms underlies some 45% of all under 5 child deaths worldwide.
- Long term: for children to thrive: there is increasing realisation that early life malnutrition contributes to the fast-growing global epidemic of non-communicable diseases (NCDs).

As more children now survive episodes of malnutrition in childhood there is increasing need to understand what causes the long term problems. Evidence on this would lead to: improved early treatment of child malnutrition; improved longer term treatment aiming to reduce long term adverse effects.

In this project we have a unique opportunity to explore three groups of children/adults in:
- Jamaica: children suffering from severe malnutrition in the 1980s have been followed up on several occasions already, with scope for further analysis from already collected data.
- Malawi: We recently followed up a group of children admitted for severe malnutrition in 2005/6. We plan to both analyse existing data in more depth: also to possible collect new data in future.
- Ethiopia: Individuals who were young children at the time of the great Ethiopia famine of 1983-85 are about to be followed up in a pilot study. Learning from the above two projects will inform and improve plans for the Ethiopia work.
We aim to understand what are the long term problems following early child malnutrition and why they occur (the 'mechanisms' by which the two problems are linked)


The work proposed in this applicaiton is background towards the above future project. There are two main activities planned

A) Review of exisiting evidence: we will search the scientific literature to better understand what other have found to date re links between early life malnutrition and adult NCDs. Through this we will identify key knowledge gaps to target in future work.

B) Collaborator meeting - we will bring together the teams working on the above three groups of children to: learn from each other and share experiences. Through this better future work will be possible and there is great potential to enhance the overall learning compared to following each group as a stand-alone.
This meeting will be organised in Ethiopia in Autumn 2019: we will invite a number of key experts to make detailed plans for future work.
The Ethiopia/Malawi/UK teams will also visit Jamaica (the most advanced/experienced group) to learn from their experience and thus help plan better future projects in Malawi and Ethiopia.

Technical Summary

Malnutrition is a major global public health problem underlying some 45% of all deaths among children aged under 5 (child u5) worldwide. Severe Acute Malnutrition (SAM) is particularly serious, affecting some 17 million children u5 and causing over 500,000 deaths/year. As well as affecting chances to survive, data also suggests that children's potential to thrive is affected by early life episodes of malnutrition. This has major implications, especially for efforts to tackle the rapidly growing epidemic of NCDs (non-communicable disease).

While intrauterine undernutrition has been linked to later life NCDs, data on the effects of child malnutrition is sparse. Some of the few long-term post-SAM follow-up studies currently that are available show interesting associations between SAM (and related forms of severe malnutrition) in childhood and processes associated with muscle function and growth, including cardiac development, and overall metabolism (especially glucose metabolism) in adulthood. These observations make it plausible that child SAM increases risk of adult NCD - but mechanisms underlying these association are far from understood.
More data matters because:
a) There are many children alive today who suffer from or have suffered from SAM: better understanding their life-course risks is vital for policy, planning and advocacy
b) Understanding SAM>NCD mechanisms could lead to improved treatments for SAM
c) Understanding SAM>NCD mechanisms could also lead to post-SAM treatments to reduce NCD risk.

This study will ultimately provide more data by learning from three unique cohorts:
- Jamaica:
- Malawi:
- Ethiopia
Working with the 3 cohorts together will enable more lesson to be learnt - to inform policy and practice in many other LMIC countries.

The requested grant is towards background literature reivews and collaborator meetings to shape details of future larger studies.

Planned Impact

The following would benefit from this reasearch

1) Local communities (including vulnerable infants/children and adults with NCD)
--> If any problems (specifically NCDs such as high blood pressure or poor glycaemic control) are identified in study participants at follow-up they will be referred for appropriate medical care, thus directly benefiting their health. We will definitely aim to follow up local communities in Ethiopia. Data is already available from Malawi and Jamaica - depending on outcomes of the investigator meeting further follow-up may be planned.
--> Awareness of NCD and links with early life malnurition will be raised in local communities through our work
--> Vulnerable infants and children would also benefit it (as we anticipate) data from this study ultimately leads to improved treatments for child malnutrition.

2) Policy makers / programme managers
- Highlighting the mechanistic links beween early life severe malnutrition and later life NCD will offer invaluable advocacy materials for policy makers and programme managers working in LMIC/emergency settings.
- Linking the two conditions will provide powerful arguments for greater investment in both preventing and treating early life malnutrition: both an important need in itself, also a way of tackling the growing epidemic of NCDs

3) Scientists & academics
By proving mechanisitc information for researchers to :
- develop better treatments for severe malnutrition.
- develop better post-treatment care packages.
...at-risk individuals and communities will directly benefit.

Publications

10 25 50
 
Description The main aim of this award was to develop a detailed proposal to explore "Links between nutrition and non-communicable disease (NCD)" in depth/over a longer time period. Already however, through meetings and networking with colleagues in Ethiopia, Jamaica and Malawi, we have made steps towards our ultimate goal of understanding and tackling the links between nutrition and NCDs:
Through the background literature review done as part of this project we have confirmed that child malnutrition has negative effects on later life / adult health and disease and increases the risk of non-communicable disease such as heart disease and diabetes. This matters because it makes tackling child malnutrition all the more important: it is not just a child health issue with short term risk of death and disease but it is also relevant for the health and wellbeing of survivors. To effectively tackle the current global epidemic of non-communicable disease (NCD), the global health community must also focus on children and child nutrition in particular.
This finding (and sharing it at networking/dissemination activities detailed in the ResearchFish submission) is especially relevant to ODA countries where:
- Child malnutrition (undernutrition) is still common
- NCDs like heart disease and diabetes are rapidly increasing and are both a current problem / will be a significant future problem.
Though our project is focused on Jamaica, Ethiopia and Malawi, the findings of the review take into account all low and middle income countries and are thus widely relevant.
Exploitation Route We have already submitted an application for follow-on work based on the data and discussion arising from this seed award. WE hope the literature review (currently being submitted for publication) will also help others in future.
Sectors Healthcare

 
Description Through sharing findings and issues raised during this seed award at meetings aimed at policy-makers/practitioners (e.g. Action Against Hunger "Research 4 Nutrition Meeting) we are already starting to raise wider awareness of the long term consequences of severe malnutrition. This being a very early stage in the project it is too early to assess wider impact of this but we anticipate that it will be relevant to a large number of LMIC settings, not just our target countries Jamaica, Ethiopia, Malawi. As per reporting guidelines: - To ensure meaningful and equal opportunties for people of different genders we have assembled a mixed team of both male and female scientists to work on the project (also scientists at different career stages. - We have not yet started field activities, but plans involve research participants of all genders and include start-up workshops to help local communities/particpants/other stakeholders engage with the work - We do not anticipate and negative consequences on gender equality - In our plans for the full study we will aim to recruit all survivors of severe malnutrition in childhood irrespective of gender and will report outcomes by gender and age. - We have a very diverse research team representing not only different genders but also different professional/personal backgrounds and nationalities. - This being only a seed grant our impacts to date are small - though we have begun engagement activities raising awareness of our research topic (the link between early child undernutrition and later life / adult NCD). We hope that this is an inital step towards influencing future health / nutrition policy and practice.
First Year Of Impact 2020
Sector Healthcare
Impact Types Policy & public services

 
Description WHO technical consultation on child wasting
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a advisory committee
Impact Technical consultation: Prevention and treatment of wasting - gaps in guidance and way forward to a holistic approach in bringing children back to healthy growth 17th - 19th December 2019 WHO HQ, Geneva, Switzerland Salle C SCOPE AND PURPOSE 1. Background Malnutrition is a major global development challenge. SDG2 aims to end by 2030 all forms of malnutrition, including wasting, stunting, overweight and vitamin and mineral deficiencies. Childhood wasting contributes to increased mortality, morbidity, impaired intellectual development, increased risk of disease in adulthood and suboptimal adult work and earning capacity. It is estimated that 49 million children under the age of 5 (U5) suffered from wasting in 2018. Of those, approximately 33 million suffered from moderate wasting, while some 16.5 million suffered from severe wasting. More than two thirds of all wasted children under 5 lived in Asia (33.8 million) and more than one quarter lived in Africa (14 million). The World Health Assembly has set a target to reduce and maintain wasting to less than 5% by 2025, on the way to full elimination by 2030. However, the prevalence of childhood wasting has been declining in a negligible way (down from 7.8% in 2012). A substantial increase in efforts would therefore be needed. The prevention and treatment of wasting and the reduction of mortality linked to wasting will require a multipronged approach, including prevention of low birth weight (LBW) and wasting in infancy and early childhood, early identification of wasting before children develop medical complications and before their nutritional status deteriorates, and scaling up treatment of wasted children. Currently, there is little understanding on the pathophysiology of wasting at the moderate end of the spectrum of wasting and the groups of infants and children at highest risk of mortality. There is also a need to identify the existing gaps in the guidance and implementation, to identify the research needed to address these gaps and to agree on what evidence is needed to be able to make recommendations to support governments in preventing and treating wasting. WHO, in collaboration with UNICEF, UNHCR and WFP is convening a technical consultation on the prevention and treatment of wasting, to review the technical framing of wasting, to discuss how to identify children at highest at risk of mortality and morbidity, to identify needs for additional guidance on prevention and treatment, as an input to the development of a UN Global Action Plan on Wasting2 2. Objectives of the meeting i. To develop the basis for an updated technical framing of wasting and agree on key questions on the prevention and treatment of wasting. ii. To discuss the evidence and remaining gaps on interventions. iii. To agree on the processes to address these gaps and propose key themes for the Global Action Plan on Wasting. 3. Outcomes of the meeting ? Information for developing an updated technical framing of wasting. ? Identification of key questions/issues on the prevention and treatment of wasting. ? Identification of evidence and research gaps. ? Information on key themes to inform the Global Action Plan on Wasting and required commitments.
 
Description Child malnutrition& Adult NCDs-Generating Evidence on mechanistic links in Jamaica, Malawi & Ethiopia to inform future policy/practice (CHANGE study)
Amount £49,819 (GBP)
Funding ID MR/T008628/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 08/2019 
End 01/2020
 
Title ChroSAM database 
Description This is data from a follow-up study of an existing cohort of ex-malnourished children aiming to describe long term outcomes following SAM (Severe Acute malnutrition) Data collection is about to be complete so that we will have linked data from: a) Original episode of malnutrition b) A 1- year follow-up study http://www.ncbi.nlm.nih.gov/pubmed/24892281 c) The current follow-up (which is the most detailed to date) The latest variables in the database include: 1) Main outcomes • Alive or dead at 7 years post-SAM • Detailed anthropometric measures, including: o Weight o Height (including standing and sitting height, lower leg length); o Circumferences of head, chest, waist, hip, upper leg and mid-upper arm; From these, measures, appropriate indices will be calculated (height-for-age; weight-for-height; BMI z-scores) 2. Early markers of chronic disease: • Cardiovascular o Blood pressure o Haemoglobin • Respiratory o Oxygen saturation o Lung function assessed by spirometry (Forced vital capacity; Forced expiratory volume in first second; forced expiratory flow 25%-75%) • Physical capacity assessed by shuttle run test (aerobic fitness); hand grip strength • Body composition assessed by bioelectrical impedance and skinfold thickness • Cognitive function o school achievement; o brain MRI (subset of patients only); • Metabolic function assessed by salivary cortisol; and venous blood for HbA1c; fasting blood glucose/glucose tolerance test (subset only); 3. Predictors of favourable or adverse long term outcomes: • Family characteristics (including parental education, employment and family size - again repeated at follow-up to assess changes from original baseline) • Socioeconomic status and household characteristics (repeated at follow-up to assess any changes from original baseline assessment) • Maternal/carer mental health (SRQ questionnaire) • Social support and wellbeing (MPSS - Multidimensional Scale of Perceived Social Support; SWBS - spiritual wellbeing scale; WHO-QoL Bref) • Disability (12 questions screen) 
Type Of Material Database/Collection of data 
Year Produced 2016 
Provided To Others? No  
Impact We are just about to finish data recruitment. The bulk of data will be reported in a PhD which I am supervising. However, we already anticipate that there will be significant "other" data left over for future students and investigators to use to look at related questions about long term outcomes following malnutrition. 2017 update The main paper has now been published. Funding allowing, we hope to continue with further outputs from this database. 2018 update We have published a further paper on lung function following severe malnutrition; have one more paper on cognitive function submitted; are planning further publications over the coming year. 2020 update As well as a MSC summer project based on this database it is one of a number of cohorts which we hope to explore in teh MRC CHANGE study looking at long term outcomes following severe malnutrition. 
 
Description 2012-2014 Malawi-Liverpool-Wellcome ChroSAM project (+support for MAMI project) + new MLW PhD 2020-2023 
Organisation Wellcome Trust
Department Malawi-Liverpool Wellcome Trust Clinical Research Programme
Country Malawi 
Sector Academic/University 
PI Contribution The ChoSAM project is based on a cohort of children recruited for my PhD study in Malawi from 2006 to March 2007. I drafted the initial concept paper underlying this proposal and am overall lead researcher on this project, supervising UCL PhD student Natasha Lelijveld, who is working on the project as her PhD (I am one of 3 supervisors and the main supervisor in the field)
Collaborator Contribution MLW hosts the ChroSAM project in Malawi. The project is funded as an £197000 extension award to MLW core grant from the Wellcome trust. This pays all project and staff costs (my salary is covered separately by my ACL funding) MLW also supported my ACL Starter Grant looking at infant malnutrition: the communications team were key partners enabling and co-authoring the qualitative parts of this project, providing both ideas and intellectual inputs as well as the critical links to community groups who were interviewed.
Impact ChroSAM project started recruiting patients in Aug 2013 - mainly internal progress reports presented so far. One abstract accepted at IAEA meeting, May 2014 (please see publications) Will be further publications/outputs late 2014. MAMI has also resulted in several poster and oral presentations to date - a paper is being planned. This project is highly multidisciplinary, involving me as project leader/PI (Public Health/Clinical background); MSc students (hence also playing a role in training future researchers); social scientists from the MLW communications team. Project has now finished - but collaboration continues. We have just sumbitted the main paper arising from this study and it is in peer review. 2017 update: The main paper from the ChroSAM study has now been published and the first (of what we hope will be numerous) secondary papers accepted. For now, this project will be closed - though I hope there will be future papers arising from the dataset and future grant applications based on the same cohort as they get older. 2020 update: As well as some further MSc project and papers arising from the ChroSAM cohort we have recently established a link with a MLW PhD researcher who will undertake further follow-up of the cohort. This is due to start in Sept 2020 and is in planning phase now. The follow-up is also linked to the CHANGE study and would be a study site for the big project if awarded.
Start Year 2012
 
Description 2012-2014 Malawi-Liverpool-Wellcome ChroSAM project (+support for MAMI project) + new MLW PhD 2020-2023 
Organisation Wellcome Trust
Department Malawi-Liverpool Wellcome Trust Clinical Research Programme
Country Malawi 
Sector Academic/University 
PI Contribution The ChoSAM project is based on a cohort of children recruited for my PhD study in Malawi from 2006 to March 2007. I drafted the initial concept paper underlying this proposal and am overall lead researcher on this project, supervising UCL PhD student Natasha Lelijveld, who is working on the project as her PhD (I am one of 3 supervisors and the main supervisor in the field)
Collaborator Contribution MLW hosts the ChroSAM project in Malawi. The project is funded as an £197000 extension award to MLW core grant from the Wellcome trust. This pays all project and staff costs (my salary is covered separately by my ACL funding) MLW also supported my ACL Starter Grant looking at infant malnutrition: the communications team were key partners enabling and co-authoring the qualitative parts of this project, providing both ideas and intellectual inputs as well as the critical links to community groups who were interviewed.
Impact ChroSAM project started recruiting patients in Aug 2013 - mainly internal progress reports presented so far. One abstract accepted at IAEA meeting, May 2014 (please see publications) Will be further publications/outputs late 2014. MAMI has also resulted in several poster and oral presentations to date - a paper is being planned. This project is highly multidisciplinary, involving me as project leader/PI (Public Health/Clinical background); MSc students (hence also playing a role in training future researchers); social scientists from the MLW communications team. Project has now finished - but collaboration continues. We have just sumbitted the main paper arising from this study and it is in peer review. 2017 update: The main paper from the ChroSAM study has now been published and the first (of what we hope will be numerous) secondary papers accepted. For now, this project will be closed - though I hope there will be future papers arising from the dataset and future grant applications based on the same cohort as they get older. 2020 update: As well as some further MSc project and papers arising from the ChroSAM cohort we have recently established a link with a MLW PhD researcher who will undertake further follow-up of the cohort. This is due to start in Sept 2020 and is in planning phase now. The follow-up is also linked to the CHANGE study and would be a study site for the big project if awarded.
Start Year 2012
 
Description College of Medicine Malawi - Nutrition Projects 
Organisation University of Malawi
Department Department of Paediatrics & Child Health
Country United Kingdom 
Sector Academic/University 
PI Contribution I have a long standing relationship with CoM Malawi, since originally working there as a volunteer paediatric registrar/lecturer in 2003-4. The link has both inspired and directly enabled my research career, hosting my PhD in 2005-8 and hosting subsequent links and projects ever since. Since the start of ACF/ACL posts I have maintained close links and have had several UCL MSc students visit Malawi to work on their projects there - all themed around my overall area of research into severe acute malnutrition / infant nutrition. We are currently collaborating on my AMS Clinical Lecturer Starter Grant - COM colleagues are co-authors on work presented at meetings to date and will be co-authors on the future papers arising.
Collaborator Contribution The CoM (Department of Paediatrics in particular) have hosted my UCL MSc students and facilitated access to patients / staff for the the project. Without this the projects would not have been possible. They have also helped with room hire for the community dissemination event which I organized as a key output of my AMS starter grant.
Impact Please see publications list: - Lelijveld et al - Ahmad et al. Other papers are in-progress (two are directly arising from the AMS starter grant: 1) Carers' and health workers' perspectives on Community Management of Acute Malnutrition (CMAM) in infants of less then 6 months: qualitative founding of a formative study from Malawi. (awaiting comments from co-authors; to be submitted to BMC Nutrition Journal) 2) Management of Acute Malnutrition in Infants aged <6 months (MAMI) in Malawi: prevalence and risk factors in an observational study (accepted for presentation at Royal College of Paediatrics Annual Meeting, April 2015. Will be submitted to peer review journal immediately after that) All the above pieces of work are already informing future research discussion / policy-discussions (e.g. in the ENN collaboration to develop assessment / patient management 'tools' for infants <6m). Hence there are already early impacts on policy/health services. 2016 update: This collaboration continues. CoM I hope will be involved in the adolescent study for which I have just been awarded a grant. We also continue collaborating on student projects. 2017 update I remain in contact with colleages at CoM. We are joint investigators on an application to look at body composition in our cohort of ex-malnourished children in Blantyre, Malawi - this is hoped to start later in 2017 (funding allowing) 2019 update - This past year I have not been out to Malawi but did have a MSc student visit over summer 2018 to work on a project looking at nutritional status of surgical patients. 2020 update - another MSc student did her MSc project on Malawi data which we hope to publish together. COM colleagues were also co-applicants on a MRC application (the full version of the CHANGE study). This is a good example of long term outcomes arising from a long established contact.
 
Description Jimma University MAMI Project (funded) & Post-malnutrition follow-up project (seeking funding) 
Organisation University of Jimma
Country Ethiopia 
Sector Academic/University 
PI Contribution I am PI on the $2.5m Eleanor-Crook Foundation funded project on infant malnutrition. It is the culmination and major step forward for the infant nutriton work I've been doing for many years now. Related to but separate from the above project, Jimma are also partners on the MRC Change study. We submitted the main application in Jan 2020 and are awaiting outcomes from a MARCH 2020 panel meeting.
Collaborator Contribution Colleagues at Jimma are leading the research locally in Ethiopia where our study is set.
Impact We have just started the project in Aug 2019 so are in year 1 developing formative work to inform our main RCT planned to start Oct 2020.
Start Year 2019
 
Description Partnership with UWI Tropical Metabolism Research Unit (TMRU) on application to study links between child malnutrition and adult NCD 
Organisation University of West Indies
Department Tropical Metabolism Research Institute
Country Jamaica 
Sector Academic/University 
PI Contribution Together with TMRU, Jimma University and MEIRU Malawi we applied to and obtained seed funding to develop a project to explore links between early child malnutrition and later life NCD. I am PI on the project and had a research assistant lead on a background systematic review / contribute to grant-writing.
Collaborator Contribution TMRU colleauges made key scientific contributions to multiple aspects of this project: - The original concept - Co-authors on the systematic review - Co-authors of the full grant application - Hosted a research planning meeting in Jamaica in November
Impact We submitted a full application to MRC in Jan 2020 and are awaiting results. Irrespective of what happens with that we hope that the collaboration can continue.
Start Year 2019
 
Description Action Against Hunger "Research for Nutrition" conference, Nov 2019 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This was a meeting linking researchers with practitioners / funders and others working in nutrition. The aim was to encouage dialogue and sharing of evidence. As well as chairing a session on infant malnutrition I also enabled a number of ex-MSc students to attend and present their summer project research. This included a systematic review on long term outcomes following malnutrition which is directly related to the CHANGE project
Year(s) Of Engagement Activity 2019
 
Description LSHTM Open day 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact This was LSHTM wide open day. Students mainly came to learn about our MSc courses (including the Nutrition MSc I'm programme Director of). But in process they also learn about LSHTM research and our nutrition research.
Year(s) Of Engagement Activity 2020
 
Description MARCH summer projects launch event 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact As part of LSHTM MARCH centre activites we held a Christmas party / summer project launch event. This involved linking current MSc students with potential projects /supervisors. This is a win/win:
- Researchers get linked to a student who can support their research
- Students get a policy/practice relevant project to work on.
I also included work on my projects in the project list: both MAMI projects and long term follow-up projects.
Year(s) Of Engagement Activity 2019
 
Description Teaching on LSHTM courses: Diploma in Tropical Medicine; Diploma in Tropical Nursing; Nutrition in Emergencies Module 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact I regularly teach on severe malnutrition on the above three courses at LSHTM. All talks are informed by / include descriptions of research I'm also engaged with and a key aim (from my perspective) is to broaden awareness of the research - and in turn to imporve policy/practice in the field of severe malnutrition. THis happen because:
- Some students go directly to research in this area (e.g. via summer project with myself; via projects with others)
- Many of our students will go onto be leading policy-makers/practitioners in their own right.
All the above begins with change in views/knowledge - as evidenced by positive feedback I get.
Year(s) Of Engagement Activity 2019
 
Description Wageningen University Study visit - Feb 2020 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Undergraduate students
Results and Impact As part of a study tour of a number of UK Universities, a group of undergrad / postgrad students from Wageningen University, Netherlands visited LSHTM for an afternoon. I was among a number of staff who shared short summaries of the research we're doing. No direct impact in short term but was helpful to broaden awareness of the research we're doing.
Year(s) Of Engagement Activity 2020