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

近几十年来，肥胖、心脏代谢疾病、哮喘、骨质疏松症和神经发育障碍的患病率不断上升，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，早期生活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）短暂的环境暴露可能对后代健康产生终身影响。表观遗传现象被认为是有害胎儿或生命早期暴露的机制，如妊娠期或幼儿期营养不足，可能会影响后代表型和暴露后数年的不良健康风险。孕妇怀孕期间的饮食是一种可改变的行为，可能影响孕产妇、新生儿和儿童的健康。然而，怀孕期间对最佳胎儿生长发育的具体饮食要求尚不清楚。此外，针对胎儿计划假说的研究主要集中在怀孕期间母亲对单一营养素的摄入。营养物质不是单独消耗的，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。根据DOHaD模式，显然需要对肥胖、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。该项目旨在通过显著扩展关于饮食、表观遗传学和后代健康之间生物标志物相互作用的知识库来推进最先进的技术。利用生命过程流行病学国际前沿的现有欧洲纵向出生队列的生物样本和数据，我们将调查母亲饮食（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）之间的复杂关系。更好地了解后代健康的营养和表观遗传生物标志物，将有机会改进饮食暴露措施，并有助于制定更有效的循证公共卫生战略，重点是在孕前、孕期和产后早期倡导健康饮食，减少肥胖，改善健康，减轻后代一系列不良健康后果的发展。

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.