Knowledge Generation

Margaret Kosek of Johns Hopkins University in the U.S. and co-investigators will generate a new biomarker panel to assess disease activity in environmental enteropathy, which causes stunted growth and malnutrition. They will analyze markers related to immune system activation and growth factors in samples derived from the children enrolled in the MAL-ED (malnutrition and enteric diseases) study in Peru, and compare them with growth profiles and diarrheal disease burden as a proxy for disease activity.

William Faubion of the Mayo Clinic in the U.S. and colleagues will develop a non-invasive test of small intestinal permeability to improve the reliability of detection of environmental enteropathy, which causes childhood growth failure. The test involves quantification of sugar absorption in urine samples using mass spectrometry, and will be validated in at risk infants in the developing world. The aim is to provide a simple, safe and inexpensive test to identify all cases of this condition on a global scale, and drive the development of preventative interventions.

Mark Manary of Washington University in the U.S. and colleagues will develop a strategy for the non-invasive diagnosis of environmental enteropathy, which causes malnutrition and growth failure in young children in the developing world. They will devise a robust protocol to isolate human RNA of the small bowel from samples of stool, and will test a broad panel of candidate biomarkers for their ability to identify environmental enteropathy with high sensitivity using samples from at risk Malawian children.

Yun Yun Gong of Queen’s University Belfast in the United Kingdom and colleagues will identify mechanistic biomarkers of child stunting caused by the dietary contaminant aflatoxin, which is common in many parts of sub-Saharan Africa. They will determine the mechanism by which aflatoxin inhibits growth in early life using blood samples and growth charts from 300 children in Gambia and analyzing the relationship between aflatoxin exposure and changes in insulin-like growth factor signaling, epigenetic marks, and gene expression.

Robin Bernstein of the George Washington University in the U.S. and colleagues will undertake one of the most detailed longitudinal studies to date to examine the effects of epigenetic and hormonal factors on growth during the first 1000 days of life. Assessment of a variety of parameters, including infectious exposures and hormone levels, as well as epigenome and transcriptome analyses will be collected from the 13th week of gestation through infant and early childhood from a cohort of 200 Gambian children.

David Mabey of the London School of Hygiene and Tropical Medicine in the United Kingdom and his team will test whether treatment with the broad-spectrum antibiotic azithromycin can prevent growth faltering linked to environmental enteropathy, which is prevalent in young children of developing countries. They will utilize a double blind, randomized, controlled trial of Malawian children aged 1-60 months, and analyze growth over a two year period after a single administration of either the antibiotic or a placebo control.

Sean Limesand of the University of Arizona in the U.S., along with co-investigators, will test whether infants with intrauterine growth restriction, caused during gestation by oxygen and nutrient deprivation, could benefit from pharmacological intervention using well-characterized adrenergic drugs to improve skeletal muscle metabolism. Intrauterine growth restriction affects around 24% of babies born in developing countries and leads to perinatal morbidity and mortality.

Theresa Gyorkos of McGill University in Canada and colleagues will investigate whether treating worm infections in lactating women has a beneficial effect on breast milk production and on infant and maternal health. They will conduct a double blind, randomized, controlled trial in Peruvian mothers following in-hospital delivery, and analyze the effect of de-worming on quantity and quality of breast milk, maternal anemia, and infant growth and morbidity, over a 24-month period.

Peter Gluckman of the University of Auckland in New Zealand and colleagues will test whether intrauterine growth retardation and childhood stunting, which are commonly seen in developing countries, are caused by epigenetic changes that can be corrected in pregnancy and infancy by modifying nutrition. Stunting is associated with many negative outcomes including decreased cognitive ability and immune function.

Daniel Roth of the Hospital for Sick Kids in Canada and colleagues will test whether endocrine factors cause stunting in early infancy. They will analyze parathyroid hyperactivity in a cohort of infants from Bangladesh, where stunting is estimated to affect almost half of all children under the age of 5. To uncover the mechanisms responsible for this hyperactivity, they will conduct a vitamin D supplementation trial and analyze maternal, cord, and infant plasma specimens for evidence of dysregulation of the parathyroid-vitamin D axis.