Placental morphology and serum biomarkers to predict adverse pregnancy outcome

描述(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的重要来源，以及源于胎儿的成人疾病。目前，有一项紧急情况 需要开发临床上有用和准确的这些不良后果的早期预测指标，以便优化临床护理。此外，未来探索旨在预防这些不良后果的治疗方法的努力能否成功，在很大程度上取决于及早识别那些风险最高的妊娠。滋养层侵袭的异常表现 而早期胎盘发育与先兆子痫、胎儿生长受限、自发早产和死产的发病机制有关。此外，由于滋养层侵袭在妊娠早期基本完成，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指标。直到最近，这一领域的研究一直被降级到间接测量早期胎盘发育，如子宫动脉多普勒。然而，三维超声的最新进展使研究人员能够以更直接的方式评估早期粗大的胎盘发育。我们最近提出了一个胎盘形态指数(PMI)，它考虑了胎儿的大小、胎盘体积和平均胎盘直径作为区分大体胎盘形态的各个组成部分的一种手段。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指标。在这项研究方案中，我们的目标是检验我们的新型超声胎盘测量在预测不良妊娠结局中的应用。此外，为了补充我们的三维超声测量，同时保持与我们的胎盘特异性方法的一致性，我们将检查结合我们的大体胎盘测量和有希望的胎盘发育的血清生物标志物的效用。胎盘生长因子和胎盘蛋白13是两种很有前途的分析物，它们由胎盘特异表达，并在胎盘早期发育中发挥关键作用。此外，它们对不良妊娠结局的发生显示出显著的预测价值，甚至早在怀孕早期就是如此。因此，我们的假设是，我们对大体胎盘发育的三维测量与已知的滋养细胞侵袭指标胎盘分析相结合，可以产生早期的“胎盘概况”，可以在临床表现出现之前很久就识别出不良妊娠结局的最大风险的怀孕。在这项研究中，我们将获得11-14周胎盘的三维超声体积组，以及母体血清样本，作为旨在开发预测不良妊娠结局的早期筛查试验的前瞻性队列研究的一部分。 公共卫生相关性：胎盘在许多不良妊娠结局中起核心作用，如先兆子痫、胎儿生长受限和围产儿死亡。本研究将结合孕妇血液中胎盘生长因子和胎盘蛋白13这两种与胎盘发育和不良妊娠结局相关的胎盘蛋白水平，探讨早期胎盘发育的三维超声测量方法预测这些不良结局的能力。我们的目标是开发一种筛查测试，可以在怀孕早期识别高危妊娠，以便优化他们的妊娠管理。

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. PUBLIC HEALTH RELEVANCE: The placental plays a central role in many adverse pregnancy outcomes, such as preeclampsia, fetal growth restriction, and perinatal death. This study will explore the ability of 3-dimensional ultrasound measures of early placental development to predict these adverse outcomes in combination with maternal blood levels of two placental proteins, placental growth factor and placental protein 13, which have been associated with both placental development and adverse pregnancy outcomes. Our goal is to develop a screening test that can identify high risk pregnancies early in gestation so that their pregnancy management can be optimized.