Non-communicable diseases (NCDs) such as heart disease and diabetes rapidly increasing in low- and middle-income countries (LMICs). These diseases are occurring at younger ages in LMICs compared with high-income countries with accompanying economic and societal costs. Between 1980 and 2014, the prevalence of diabetes doubled in sub-Saharan Africa, India and China and is now higher there than in many high-income countries. 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. With rapid socio-economic transition, LMICs are experiencing not only undernutrition and low birth weight, but also increased weight gain during later childhood and adolescence. The consequence of this combination results in women in these countries entering pregnancy with poorer nutrition and increased rates of diabetes during pregnancy. It is therefore possible that measures to improve the nutrition of young women before and during pregnancy may have long-term beneficial effects. Research has also shown that chronic inflammation (a normally protective response of the body to injury or infection) has been associated with NCDs including diabetes and heart disease. Nutrition plays a key role in the regulation of this inflammatory response. It has been shown that diets consisting of a greater intake of red meat, high-fat products, refined grains, and simple carbohydrates can result in higher levels of markers of inflammation, even in the absence of injury or infection. 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 maternal nutrition and well-being 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. As part of the main study, we will collect a range of biological samples (blood, buccal and vaginal swabs, urine, stool, cord blood and placenta) from the women/mothers, fathers and children. In this study, we will undertake analyses of a selection of these biological samples. We aim to understand the nutritional factors (such as body size and diet) that affect inflammation in young women in three countries (China, India and South Africa). We will explore whether inflammation is related to maternal complications such as diabetes during pregnancy, and whether it affects fetal growth. We will also assess whether the intervention reduces inflammation and the risk of maternal complications, and improves fetal growth. Finally, we will explore the pathways by which nutrition, inflammation and NCDs are related. The findings will have important global policy implications for maternal and child health as the studies cover urban and rural populations in various stages of socio-economic transition.

Our overall hypothesis is that sub-optimal maternal nutritional status leads to an increased non-communicable disease (NCD) risk in both the mother and child, and this is mediated through an increased inflammatory load before and during pregnancy. Poor nutritional status among women in low- and middle-income countries (LMICs), reflected by recent dietary changes and the 'double burden of malnutrition', results in a chronic inflammatory state. Among pregnant women, this inflammatory state leads to pregnancy complications (gestational diabetes, hypertensive disorders and pre-term birth) and placental changes that impair fetal growth. These disrupt fetal development, and increase newborn adiposity and the risk of later NCDs. Nutritional interventions before and during pregnancy will reduce inflammation, prevent pregnancy complications and improve newborn body composition. Specific objectives: 1. To determine the nutritional drivers of inflammatory load among pre-conceptional women and interactions with other influences on inflammation 2. To establish relationships between nutritional status, inflammatory load and pregnancy/birth outcomes and identify the mechanistic pathways involved 3. To determine whether interventions to optimise maternal nutritional status reduce pregnancy complications and improve fetal and newborn outcomes, and whether these effects are mediated by decreased inflammatory load 4. To establish associations of maternal nutritional status and inflammatory load with placental phenotypes, and determine the impact of the intervention. Capacity building is a key component of our project; it will increase capacity, especially among junior researchers, to undertake mechanistic studies in China, India and South Africa while UK investigators will gain experience in global health research.