Kevin Kain of the University Health Network and the University of Toronto in Canada will investigate malaria infections of the placenta to reveal specific roles of the immune response that lead to preterm birth, low birth weight, and stillbirth. This project will focus on discovering biomarkers to identify at-risk pregnancies as well as new interventions to prevent adverse pregnancy outcomes. Funding partners: Global Alliance to Prevent Prematurity and Stillbirth (GAPPS) and Bill & Melinda Gates Foundation.

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. Using epigenetic analyses, and clinical and epidemiological approaches in stunted and control children from Jamaica, Ghana and Singapore they will identify underlying pathophysiological mechanisms of stunting that can act as targets for intervention. The long-­term goal is to prevent infant stunting and its associated adverse consequences.

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. Candidate biomarkers will be validated in an in vitro cell model of human liver, which is the primary target of aflatoxin, and used to drive future intervention strategies, such as hand-sorting food to reduce contamination, for ultimately improving child health.

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. These extensive data sets will reveal the mechanisms of growth faltering, and will aid in the development of targeted interventions to promote healthy infant growth and development.