THE PROBLEM: Child malnutrition is a major global public health problem and includes both undernutrition and overweight/obesity. Wasting (low weight-for-height) is a particularly severe form of undernutrition. Affecting some 49 million children globally, it contributes to 900,000 deaths per year in children aged <5 years (12% of total deaths). Whilst severe malnutrition treatment programmes do exist, problems limiting their success include the need to: a) ENSURE THAT CHILDREN THRIVE AS WELL AS SURVIVE Current programmes focus on averting the immediate risks of malnutrition-associated death. They don't account for increasing evidence that survivors often fail to thrive and are at greater risk of non-communicable disease (NCD) in later life e.g. heart disease, diabetes and obesity. Mechanisms causing this are poorly understood. b) UNDERSTAND & MEASURE MORE MEANINGFUL OUTCOMES Current programmes focus on return to normal weight as a marker of success. What really matters however is health. Predicting future ill health is especially difficult since risks laid down in childhood do not become apparent as adult NCD till many years later. c) QUESTION ASSUMPTIONS ABOUT WEIGHT GAIN Current programmes often see rapid return to normal weight as desirable and thus encourage fast catch-up growth. However, studies in high income countries show that too rapid a weight gain in small infants causes harm by increasing risk of future NCDs. Whether this also applies to low-income settings is unknown. THE PLAN: AIMS: To improve future treatment programmes by better understanding how child malnutrition affects the risk of long-term (adult) NCD. OBJECTIVES: 1) To understand how the speed and pattern of post-malnutrition weight gain affects the risks of adult NCD 2) To develop simple blood/urine tests to predict which survivors of child malnutrition are most at risk of future NCD THE TEAM: We will bring together teams from 4 countries: Jamaica, Malawi, Ethiopia, UK and combine clinical and lab data from 4 groups (cohorts) of adolescents/adults who survived early life malnutrition. In Ethiopia and Malawi, we will recruit 2 more cohorts of at-risk infants so we can learn from their progress. Combining these datasets and bringing together varied scientific skills and disciplines will achieve together what no one team could achieve alone. THE BENEFITS: 1) PROGRESS TOWARDS THE 2030 SUSTAINABLE DEVELOPMENT GOALS (SDGs) If we succeed in our aim of informing better future treatment programmes we thus contribute to two major SDGs and their targets: >>SDG 2 (END HUNGER) >> SDG 3 (GOOD HEALTH & WELL-BEING) These in turn impact numerous others e.g. education, economic development 2) ENHANCED MALNUTRITION-RELATED ADVOCACY Effective advocacy is vital to generate the sufficient political will and sufficient resources to tackle malnutrition. The 'double-burden' of malnutrition (i.e. coexistence of undernutrition alongside overweight/obesity/NCDs) is increasingly common even in the world's poorest countries. By describing how one form affects the other, we hope that researchers, policy-makers and nutrition programmes managers will better be able to balance short vs long term risks and focus on 'double-duty' actions benefitting both. This could open up valuable new funding streams. It could also be a more effective and cost-effective solution to the global NCD epidemic. 3) IMPROVED SEVERE MALNUTRITION TREATMENT PROGRAMMES Likely changes would be minor and thus easily/rapidly scalable, e.g. use of the same therapeutic foods but prescribed at lower dose so that weight recovery is neither too slow nor too fast. 4) NEW BLOOD/URINE TESTS TO MEASURE NCD RISK IN MALNOURISHED CHILDREN Being able to measure a problem is key to tackling it. Simple new tests arising from our work would enable researchers/programmers to better understand if nut.>NCD programmes are succeeding.

The overall aim of our project is to improve future severe malnutrition treatment programmes by better understanding the mechanisms linking infant/child malnutrition to longer-term (adult) NCD (non-Communicable-disease) Objectives towards this are: 1. To understand how post-malnutrition weight gain (PMWG) affects the risk of cardiometabolic NCD: a. How does the timing of an episode of malnutrition influence this risk? b. How does the severity of malnutrition influence this risk? c. How do different patient management approaches influence this risk? 2. To develop biomarkers for predicting NCD risk in survivors of child malnutrition by: a. Describing the biochemical characteristics of malnutrition survivors, differentiating those with/without NCD. b. Describing the biochemical profiles of different patterns of PMWG c. Identifying biomarkers common to different patterns of PMWG and NCD risk in survivors We deliberately focus on PMWG as our key ""nutrition>>NCD"" mechanism since potential for it to be directly modifiable is high. This would be done via small, hence scalable, changes to the dose of therapeutic food prescribed in severe malnutrition treatment packages. Given that only 10 years remain utill the 2030 Sustainable Development Goal targets (Goal 2 is ""Ending Hunger"" and Goal 3 is ""Good Health and Well-being"" which includes the aim to reduce by 1/3 premature mortality from NCDs through prevention and treatment) we believe that this potential for GRIPP (Getting Research into Policy/Practice) is important. Whilst exploring PMWG as a mechanism, we will also obtain valuable data on underlying biochemical/metabolic mechanisms underlying recovery from severe malnutrition.