Mechanisms of intergenerational nutritional programming of non-communicable diseases in three countries: a Healthy Life Trajectories Initiative study. Non-communicable diseases (NCDs) such as heart disease and diabetes are rapidly increasing in low- and middle-income countries (LMICs). These diseases are occurring at younger ages in LMICs compared to high-income countries, with accompanying economic and societal costs. There are now ~166 million people with diabetes in India and China alone (40% of the world's total). Current approaches to preventing diabetes or heart disease focus on weight reduction and increased physical activity in middle-aged adults with existing risk factors such as obesity or high blood pressure. While such approaches offer some benefit to the individual, they do little to address the risk in future generations.    Research from many countries across the world has shown that low birth weight and poor growth of the fetus in the womb is related to an increased risk of developing diabetes and heart disease in later life. These effects are exacerbated by greater weight gain during childhood, adolescence or adulthood. It is suggested that undernutrition during critical periods of early development permanently alters the structure and function of the body's tissues and organs ('programming'), leading to an increased vulnerability to disease in later life. It is therefore possible that measures to optimise the health of young women before and during pregnancy, and measures to optimise the growth of infants and young children may have long-term beneficial effects on the health of the children.   In this context, the Healthy Life Trajectories Initiative (HeLTI) programme was set up as a joint initiative funded by the Canadian Institutes of Health Research, Department of Biotechnology (India), Medical Research Council (South Africa) and the National Natural Science Foundation (China), in collaboration with the World Health Organisation. There are four separate but harmonised intervention studies in Mysore (India), Johannesburg (South Africa), Shanghai (China) and two provinces in Canada. The studies will test the concept that interventions addressing multiple domains of health spanning from before pregnancy, and continued through pregnancy and after birth will improve maternal and child health including the long-term well-being of the child. Our main outcome is a measure of adiposity (fat mass in relation to height) at five years of age in the child. While the exact intervention packages vary by country to ensure cultural and contextual appropriateness, they are all unified by both the overall aim of the intervention and approach. The studies are at slightly different points - two of the studies are in the preparatory phase while the other two have started the main study.   As part of the main study, we will be collecting a range of biospecimens (blood, buccal and vaginal swabs, urine, stool, cord blood and placenta) from the women/mothers, fathers and children. Under this grant, we would like to undertake analyses of a selection of these biological samples, in order to understand how early life factors impact long-term health. In this outline call, we will standardise our procedures for processing biological samples, and finalise our plans for analyses. The results will help us in understanding the mechanisms by which poor fetal growth and undernutrition leads to NCDs in later life. The findings will have important global policy implications as the studies comprise Asian, African and Caucasian populations. The Global Challenges Research Fund (GCRF) supports cutting-edge research to address challenges faced by developing countries. The fund addresses the UN sustainable development goals. It aims to maximise the impact of research and innovation to improve lives and opportunity in the developing world.