本课题组前期病例-对照研究提示孕妇睡眠与子代先天性心脏病（Congenital heart disease,CHD）发病相关。基于此发现，本项目于孕前、孕早期多维度评估睡眠参数，前瞻性评估睡眠参数及孕前→孕早期参数变化与CHD发生之间的关联模式。以褪黑素为内暴露，观察睡眠对褪黑素分泌和表达的影响，以“Nodal-Smads-Pitx2”信号路径为生物机制效应指标，建立褪黑素作用于该信号系统的机制模型；结合人胚胎干细胞心肌分化模型，阐述褪黑素参与胚胎心脏细胞分化及形态结构形成的分子机制。综合上述，以褪黑素激活Nodal信号系统为切入点，构建暴露-机制-效应之间的数学模型，论述母亲孕期睡眠参与子代心脏发育调控的生理基础。研究首次比较系统阐述孕期睡眠影响胚胎心脏发育的生物学效应及分子机制，有望在CHD的病因学和孕期睡眠健康效应论述上取得新进展，对于丰富孕期保健理论知识和促进优生优育意义重要。

Our previous case-control study found that sleep during pregnancy was associated with congenital heart disease (CHD) in offsprings. Based on the finding, a prospective cohort study is specifically designed to observe sleep parameters across multiple dimensions before and in the first trimester of pregnancy, and then to examine the longitudinal associations of sleep and its trend with the incidence of CHD. Furthermore, the biological mechanisms underlying the associations would be explored and interpreted: ① how sleep during pregnancy affects the secretion and expression of melatonin; ② if melatonin mediates the activation of “Nodal-Smads-Pitx2” signaling pathway; and, particularly, ③ how melatonin promotes the differentiation of embryonic stem cell to heart specific progenitor cell, and how melatonin governs the heart morphogenesis. Based on all the above, the relationship mathematical model regarding melatonin linking maternal sleep and offspring CHD would be established. In summary, this study aim to systematically examine the role of sleep during peri-conception period in the embryonic heart development, which would foster new progress in the etiology of CHD, meanwhile, would promote the understanding of health effect of sleep during pregnancy on the development of offspring. All the evidence would be significant to enrich perinatal and prenatal health care knowledge which can be used in clinical practices in order to enhance aristogenesis and stirpiculture.