Placental morphology and serum biomarkers to predict adverse pregnancy outcome

描述（由申请人提供）：不良妊娠结局，如先兆子痫、胎儿生长受限和早产，仍然是围产期发病率和死亡率以及胎儿源性成人疾病的重要来源。目前，紧急 需要开发一种临床上有用的和准确的早期预测这些不良后果，使临床护理可以优化。此外，未来探索旨在预防这些不良结局的治疗方法的研究工作的成功在很大程度上取决于早期识别那些风险最大的妊娠。滋养层细胞浸润异常 早期胎盘发育与先兆子痫、胎儿生长受限、自发性早产和死胎的发病机制有关。此外，由于滋养层细胞的侵袭在孕早期结束时基本完成，因此基于超声的早期胎盘发育生物标志物是预测不良结局的有吸引力的候选者。直到最近，这一领域的研究一直被降级为早期胎盘发育的间接措施，如子宫动脉多普勒。然而，三维超声检查的最新进展使研究人员能够以更直接的方式评估早期胎盘发育。我们最近提出了一个胎盘形态指数（PMI），认为胎儿的大小，胎盘体积和平均胎盘直径作为一种手段，区分各种成分的总胎盘形态。事实上，我们的试点数据支持在11-14周测量的PMI作为不良妊娠结局的重要预测因素。在这项研究中，我们的目的是检查我们的新的超声胎盘措施在预测不良妊娠结局的效用。此外，为了补充我们的三维超声测量，同时与我们的胎盘特异性方法保持一致，我们将研究将我们的总体胎盘测量与胎盘发育的有希望的血清生物标志物相结合的效用。胎盘生长因子和胎盘蛋白13这两种有前景的分析物由胎盘特异性表达，并在早期胎盘发育中发挥关键作用。此外，它们对不良妊娠结局的发生具有显著的预测价值，甚至早在妊娠早期。因此，我们的假设是，我们的总体胎盘发育的三维测量与已知是滋养层细胞侵袭指标的胎盘分析物的组合可以产生早期的“胎盘概况”，其可以在临床表现出现之前很久就识别出具有最大不良妊娠结局风险的妊娠。在这项奋进，我们将获得11-14周时胎盘的三维超声体积集以及母体血清样本，作为前瞻性队列研究的一部分，旨在开发一种早期筛查试验，用于预测不良妊娠结局。

DESCRIPTION (provided by applicant): Adverse pregnancy outcomes, such as preeclampsia, fetal growth restriction, and preterm birth, continue to be significant sources of perinatal morbidity and mortality, as well as adult diseases with fetal origin. Currently, there is an urgent need to develop a clinically useful and accurate early predictor of these adverse outcomes so that clinical care can be optimized. Furthermore, the success of future investigative efforts exploring therapies aimed at preventing these adverse outcomes is largely dependent on the early identification of those pregnancies at greatest risk. Abnormalities in trophoblastic invasion and early placental development have been implicated in the pathogenesis of preeclampsia, fetal growth restriction, spontaneous preterm birth and stillbirth. Moreover, as trophoblastic invasion is largely completed by the end of the first trimester, ultrasound-based biomarkers of early placental development are appealing candidates for predictors of adverse outcomes. Until recently, research in this area has been relegated to indirect measures of early placental development, such as uterine artery Doppler. However, recent advances in 3-dimensional sonography have allowed investigators to assess early gross placental development in a more direct manner. We have recently proposed a placental morphology index (PMI) which considers fetal size, placental volume and mean placental diameter as a means of discriminating between various components of gross placental morphology. In fact, our pilot data support PMI measured at 11-14 weeks as a significant predictor of adverse pregnancy outcomes. In this research proposal, we aim to examine the utility of our novel sonographic placental measures in the prediction of adverse pregnancy outcomes. Furthermore, to supplement our 3- dimensional sonographic measures while remaining consistent with our placenta-specific approach, we will examine the utility of combining our gross placental measures with promising serum biomarkers of placental development. Two such promising analytes, placental growth factor and placenta protein 13, are specifically expressed by the placenta and play critical roles in early placental development. Moreover, they have shown significant predictive value for the occurrence of adverse pregnancy outcomes, even as early as the first trimester. Thus, it is our hypothesis that the combination of our 3-dimensional measures of gross placental development with placental analytes known to be indicators of trophoblastic invasion can yield an early 'placental profile' that can identify pregnancies at greatest risk for adverse pregnancy outcomes long before the clinical manifestations arise. In this research endeavor, we will obtain 3-dimensional ultrasound volume sets of the placenta at 11-14 weeks, as well as a maternal serum sample, as part of a prospective cohort study aimed at developing an early screening test for the prediction of adverse pregnancy outcomes.