基于足月低出生体重的胎儿生长受限早期标识物的识别与验证及作用机制研究

胎儿生长受限(FGR)是产科常见病征，若能早识别诊治，可改善不良出生结局，但目前缺乏早期有效识别的方法。既往FGR标识物的研究多用小于胎龄儿的定义，且未与胎盘异常结合，导致假阳性高。最新研究表明FGR与胎盘功能障碍有关，FGR早期识别的标识物应与胎盘异常关联。另足月低出生体重(FT-LBW)主要源于FGR，属于病理性，更适于研究FGR。本课题近期发现胎盘大小分别中介了孕晚期母血炎性因子和胎盘DNA甲基化与FT-LBW的关系。据此，本项目拟开展基于出生队列的巣式病例对照研究，选FT-LBW与足月正常体重为研究对象，通过检测孕早期母血全基因组甲基化和炎性因子筛选出与胎盘异常和FGR关联的标识物；然后扩大样本验证候选标识物，并探明候选标识物、胎盘结构功能特征与FT-LBW间关系及候选标识物的作用机制，为尽早识别FGR提供新方法，实现早诊早治，降低不良出生结局发生，达到优生目的，具有很好的实用价值

Fetal growth restriction (FGR) is a common obstetric symptom, early identification, diagnosis and treatment of which can improve adverse birth outcomes, but currently there is no effective methods to early identify FGR. Most of previous studies on FGR markers have defined FGR according to small-for-gestational-age and failed to combine with placental abnormalities, resulting in high false positives. The latest research indicates that FGR is related to placental insufficiency, and its early recognition should get placenta related markers involved. Meanwhile, full term low birth weight (FT-LBW) mainly origins from FGR, which is pathological and more suitable for study of FGR. Recently, our group found that the size of placenta mediated the association between inflammatory factors in maternal blood as well as the relationship of DNA methylation in placenta and FT-LBW. Therefore, we plan to conduct this nested case-control study based on birth cohort and select the FT-LBW as cases and full term normal birth weight (FT-NBW) as controls, to screen out the markers associated with placenta and FT-LBW by testing whole genome DNA methylation and inflammatory factors in maternal blood in the first trimester. Then we will expand the sample size to validate the above candidate markers, and explore relationships of the candidate markers, functional and morphological characteristics of placenta and FT-LBW, as well as their acting mechanisms. This may provide a new method for identification of FGR, which has great value in realizing its early diagnosis and treatment, improving the adverse birth outcomes and finally achieving the purpose of eugenics.