According to the latest global estimates undernutrition is a contributory cause to 45% of all child deaths. Undernutrition affects all stages of the lifecourse and has strong intergenerational echoes. The size and nutritional status of parents has a lifelong influence on their children with a mother’s nutrition at conception, in pregnancy and as she breastfeeds her baby being particularly critical.
Stunting among children, low birthweight and anaemia rates are used to assess a country’s progress in combatting undernutrition. The Gambia succeeded in meeting the Millennium Development Goals for improving child nutrition, but stunting rates are still high (~30%) and anaemia rates among women and children are very high. Meeting the new Nutrition Targets 2025 set by WHO will be extremely challenging unless new pathways to intervention can be found.
The Nutrition Theme at MRC Unit The Gambia at LSHTM concentrates on identifying, and then developing, next-generation nutrition interventions through discovery science that will inform a clearer understanding of the basic mechanisms linking diet and disease. Non-specialists will frequently assume that the causes of malnutrition are already well understood and that rectifying the situation simply requires the efficient implementation of known interventions. However, meta‐analyses of major intervention trials in pregnancy, lactation and childhood (with crucial outcomes such as birthweight, preterm birth, pre‐eclampsia, stillbirths, neonatal deaths, child survival, stunting and anaemia, etc) have generally revealed very disappointing outcomes. The factors at play are clearly more complex than hitherto assumed and require fresh insights to steer novel therapeutic pathways.
Our research on iron, infection and anaemia – underpinned by the discovery of hepcidin as the master regulator of iron – radically transforms nutritionists’ understanding of the etiology of anaemia, and hence how to combat it. Our epigenetic research into the profound effect of a mother’s nutritional status at the time she conceives a baby moves the focus from pregnancy to pre-conception. These are examples of how we seek to trace a path towards better nutritional health in low-income populations.
Professor Andrew Prentice
Andrew Prentice was born and raised in Uganda and educated in East Africa and the UK. He graduated in Biochemistry followed by a PhD in Nutrition from Darwin College, Cambridge. His first post-doc position was in MRCG Keneba almost 40 years ago. After 15 years leading the Energy Regulation and Obesity Group at the MRC Dunn Clinical Nutrition Centre in Cambridge he created the MRC International Nutrition Group at LSHTM where he is Professor of International Nutrition, and refocused all his attention on global health research. With the full integration of MRC Keneba into MRCG in 2015 he became the Nutrition Theme leader.
- Integration to Implementation and the Micronutrient Forum: A Coordinated Approach for Global Nutrition. Case Study Application: Safety and Effectiveness of Iron Interventions
Paramount among the challenges to our ability to address the role of food and nutrition in health promotion and disease prevention is how to design and implement context-specific interventions and guidance. The Integration to Effective Implementation (I-to-I) concept is intended to address the complexities of the global health context through engagement of the continuum of stakeholders involved in the food and nutrition enterprise. The 2014 Micronutrient Forum (MNF) Global Conference held in Addis Ababa, Ethiopia, in June 2014 offered the opportunity to apply the I-to-I approach with the use of current concerns about the safety and effectiveness of interventions to prevent and treat iron deficiency (ID) as a case study. ID is associated with a range of adverse outcomes, especially in pregnant and nonpregnant women, infants, and primary school-age children. Strategies to combat ID include iron supplementation, multiple micronutrient powders, and food-based interventions to enhance dietary iron intake. Recent reports indicate potential increased adverse risks when iron is provided in areas with high infection burdens (e.g., malaria). This paradox has weakened iron intervention programs. Furthermore, the selection and interpretation of available biomarkers for assessing iron nutrition have been found to be compromised by the inflammatory process. These issues highlight the need for a comprehensive approach that considers basic biology, assessment, interventions, and how these can be translated into appropriate programs and policies. The application of the I-to-I with the use of the MNF offered an opportunity to explore how that might be achieved.
- The effect of BCG on iron metabolism in the early neonatal period: A controlled trial in Gambian neonates.
Bacillus Calmette-Guerin (BCG) vaccination has been reported to protect neonates from non-tuberculous pathogens, but no biological mechanism to explain such effects is known. We hypothesised that BCG produces broad-spectrum anti-microbial protection via a hepcidin-mediated hypoferraemia, limiting iron availability for pathogens. To test this we conducted a trial in 120 Gambian neonates comparing iron status in the first 5-days of life after allocation to: (1) All routine vaccinations at birth (BCG/Oral Polio Vaccine (OPV)/Hepatitis B Vaccine (HBV)); (2) BCG delayed until after the study period (at day 5); and (3) All routine vaccinations delayed until after the study period. Vaccine regime at birth did not significantly impact on any measured parameter of iron metabolism. However, the ability to detect an effect of BCG on iron metabolism may have been limited by short follow-up time and high activation of the inflammatory-iron axis in the study population.
- Maternal nutrition at conception modulates DNA methylation of human metastable epialleles.
In experimental animals, maternal diet during the periconceptional period influences the establishment of DNA methylation at metastable epialleles in the offspring, with permanent phenotypic consequences. Pronounced naturally occurring seasonal differences in the diet of rural Gambian women allowed us to test this in humans. We show that significant seasonal variations in methyl-donor nutrient intake of mothers around the time of conception influence 13 relevant plasma biomarkers. The level of several of these maternal biomarkers predicts increased/decreased methylation at metastable epialleles in DNA extracted from lymphocytes and hair follicles in infants postnatally. Our results demonstrate that maternal nutritional status during early pregnancy causes persistent and systemic epigenetic changes at human metastable epialleles.