Mechanisms of intergenerational nutritional programming of non-communicable diseases in three countries: a Healthy Life Trajectories Initiative study.

心脏病和糖尿病等非传染性疾病在低收入和中等收入国家迅速增加。与高收入国家相比，这些疾病在中低收入国家发生的年龄更小，并伴随着经济和社会成本。目前仅在印度和中国就有1.66亿糖尿病患者（占世界总数的40%）。目前预防糖尿病或心脏病的方法侧重于减轻体重和增加有肥胖或高血压等危险因素的中年人的体育活动。虽然这些方法给个人带来了一些好处，但对解决后代的风险却收效甚微。来自世界上许多国家的研究表明，出生体重过低和子宫内胎儿生长不良与晚年患糖尿病和心脏病的风险增加有关。在儿童期、青春期或成年期体重增加会加剧这些影响。据认为，在早期发育的关键时期营养不良会永久性地改变身体组织和器官的结构和功能（“编程”），导致在以后的生活中更容易患病。因此，优化怀孕前和怀孕期间年轻妇女健康的措施，以及优化婴幼儿成长的措施，可能对儿童健康产生长期的有益影响。在此背景下，健康生活轨迹倡议（HeLTI）项目由加拿大卫生研究院、印度生物技术部、南非医学研究理事会和中国国家自然科学基金会与世界卫生组织合作，共同资助。在迈索尔（印度）、约翰内斯堡（南非）、上海（中国）和加拿大的两个省有四个独立但协调的干预研究。这些研究将检验这样一个概念，即从怀孕前到怀孕期间和出生后，针对多个健康领域的干预措施将改善孕产妇和儿童健康，包括儿童的长期福祉。我们的主要结果是测量5岁儿童的肥胖（脂肪量与身高的关系）。虽然具体的干预方案因国家而异，以确保文化和环境的适宜性，但干预的总体目标和方法都是统一的。这些研究的阶段略有不同——其中两项研究处于准备阶段，而另外两项研究已经开始了主要研究。作为主要研究的一部分，我们将收集妇女/母亲、父亲和儿童的一系列生物标本（血液、口腔和阴道拭子、尿液、粪便、脐带血和胎盘）。在这笔拨款下，我们将对精选的这些生物样本进行分析，以了解早期生活因素如何影响长期健康。在这个大纲电话会议上，我们将标准化处理生物样本的程序，并最终确定我们的分析计划。这些结果将有助于我们了解胎儿生长不良和营养不良导致以后生活中非传染性疾病的机制。这些研究结果将对全球政策产生重要影响，因为这些研究涵盖了亚洲、非洲和高加索人口。

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.