HDHL-Biomarkers: Early life programming of childhood health (ALPHABET)

近几十年来，肥胖症、心脏代谢疾病、哮喘、骨质疏松症和神经发育障碍的发病率不断上升，不能完全用遗传或成人生活方式因素来解释。越来越多的证据表明，生命早期暴露于环境因素会影响后代的健康。根据健康和疾病的发育起源假说，在发育的关键时期（如胎儿和婴儿早期阶段）短暂的环境暴露可对后代健康产生终身影响。表观遗传现象被认为是一种机制，通过这种机制，有害的胎儿或生命早期暴露，如怀孕或幼儿期的营养不良，可能会影响后代的表型和暴露后数年的不良健康风险。孕妇在怀孕期间的饮食是一种可以改变的行为，可能会影响产妇、新生儿和儿童的健康。然而，在怀孕期间的具体饮食要求，以最佳的胎儿生长和发育是未知的。此外，解决胎儿编程假设的研究集中在怀孕期间母体摄入的单一营养素。营养素不是孤立消费的，因此，研究反映整个饮食的多种饮食成分的综合影响可能具有重要的公共卫生意义。显然需要根据卫生部的模式，对肥胖症、相关的心脏代谢疾病和其他慢性非传染性疾病进行初级预防。该项目旨在通过显着扩大有关饮食，表观遗传学和后代健康的生物标志物之间的相互作用的知识基础来推进最先进的技术。利用生物样本和数据，从现有的欧洲纵向出生队列在国际前沿的生命周期流行病学，我们将调查产妇饮食之间的复杂关系，（由饮食质量和饮食炎症潜力的新指数定义），后代健康结果（包括肥胖、骨骼、心脏代谢、呼吸和神经发育健康）和表观遗传模式（DNA甲基化）从出生到整个童年。更好地了解后代健康的营养和表观遗传生物标志物将提供机会，以完善饮食暴露措施，并帮助制定更有效的循证公共卫生战略，重点是倡导在怀孕前、怀孕和产后早期的健康饮食，以减少肥胖，改善健康，并减少后代出现一系列不良健康后果。

The rising prevalence of obesity, cardiometabolic disease, asthma, osteoporosis and neurodevelopmental disorders over recent decades cannot be fully explained by genetic or adult lifestyle factors. Increasing evidence suggests that early life exposure to environmental factors influences offspring health. According to the Developmental Origins of Health and Disease (DOHaD) hypothesis transient environmental exposures during critical periods of development (e.g. fetal and early infant phases of life) can elicit lifelong effects on offspring health. Epigenetic phenomena have been proposed as mechanisms by which detrimental fetal or early life exposures, such as suboptimal nutrition during pregnancy or early childhood, may affect offspring phenotype and risk of adverse health years after exposure. Maternal diet during pregnancy is a modifiable behaviour that could impact on maternal, neonatal and child health. However the specific dietary requirements during pregnancy for optimal fetal growth and development are unknown. Furthermore studies addressing the hypothesis of fetal programming have focused on maternal intake of single nutrients during pregnancy. Nutrients are not consumed in isolation, thus examining the combined effects of multiple dietary components reflecting the whole diet could have important public health implications. There is a clear need for primary prevention of obesity, related cardiometabolic conditions and other chronic non-communicable diseases based on the DOHaD paradigm. This project aims to advance the state-of-the-art by significantly expanding the knowledge base regarding interactions between biomarkers of diet, epigenetics and offspring health. Utilising biological samples and data from existing European longitudinal birth cohorts at the international forefront of lifecourse epidemiology we will investigate the complex relationships between maternal diet (defined by dietary quality and a novel index of dietary inflammatory potential), offspring health outcomes (including adiposity, bone, cardiometabolic, respiratory and neurodevelopmental health) and epigenetic patterns (DNA methylation) from birth throughout childhood. Better understanding of nutritional and epigenetic biomarkers of offspring health will afford opportunities to refine dietary exposure measures and to aid development of more effective evidence-based public health strategies with an emphasis on advocating a healthy diet in pre-pregnancy, pregnancy and early postnatal life, to reduce obesity, improve health and attenuate development of a range of adverse health outcomes in future generations.