Placental shape features, gestational timing and maternal and infant health

描述(由申请人提供)：胎盘的发育是妊娠结局的主要决定因素，包括早产、先兆子痫和胎儿生长/出生体重。反过来，据报告，下一次怀孕的风险以及各种儿童和成人健康结果的(新生儿)风险都是由妊娠结果来预测的，这些结果可作为宫内环境是否充足的指标。我们建议全面测量胎盘形状以更直接地评估宫内环境，并开发了用于这一任务的图像分析软件工具。有证据表明，早产和先兆子痫等重大公共卫生问题起源于早期妊娠，源于亚临床病理，为无法挽回的结果“铺平了道路”。越来越多的流行病学证据将胎盘发育与儿童和成人的健康结局联系起来，但这些研究仅限于传统的胎盘重量及其导数(例如胎儿-胎盘重量比)的测量，没有报道一致的结果。目前对胎盘形状的“金标准”测量包括胎盘形状的二分法描述(如“圆形”/“椭圆形”和“不规则”)，并且仅采用一对表面直径、一种胎盘片厚度测量以及脐带插入到最近盘片边缘的距离。胎盘形状最复杂，有偏离中心的脐带、不规则的周长和不同的胎盘厚度，这些胎盘在怀孕期间可能是生长最不稳定的；然而，按照目前的“黄金标准”衡量，这些最糟糕的胎盘可能是与“胎儿起源”辩论最密切相关的胎盘，也可能是与理解先兆子痫和早产等疾病的起源最密切相关的胎盘，这些疾病似乎起源于怀孕早期。我们最近的工作表明：1)胎盘形状异常与胎盘效率降低相关，并可能在妊娠早期被确定；2)不同形状似乎是由于妊娠不同时期胎盘发育的扰动而引起的；3)11-14周时超声测量的绒毛膜板特征与足月时观察到的相似特征显著相关。我们的软件工具测量分娩的胎盘，并“倒带电影”，以确定导致胎盘偏离“正常”胎盘生长的妊娠应激源(S)的时机和程度。它使用胎盘绒毛膜表面和切片的数字.jpg照片更全面地捕捉复杂的胎盘形状和血管结构，这些照片可以在任何医院使用数码相机和锋利的刀进行准备，而且详细但仍然足够紧凑，可以很容易地通过电子邮件发送到中央诊断机构进行分析。这样的方法有望在患者和机构中复制，并有效。另一个临床用途是概念前咨询和对后续怀孕的监测，因为先兆子痫和早产可能会复发。这一阶段SBIR的目标是完成我们图像分析软件工具的开发，并使用北卡罗来纳大学教堂山分校(UNC PIN)的怀孕、感染和营养研究(UNC PIN)数据集和美国国家儿童研究(NCS)先锋胎盘项目的675例各约700例的子样本进行验证。这项建议与我们的NCS形成性研究建议的不同之处在于，这项建议仅限于开发完全来自(2D)数字图像的软件和建模方法，而NCS建议侧重于研究从3D扫描仪获得的3D形状。 与公共卫生相关：任何类型的复杂妊娠都有再次怀孕的风险，并对儿童造成终身健康风险，但最常见的是临床上“健康”的妇女。畸形的胎盘形状可以在出生时准确和可靠地测量，但目前还不是，以作为识别、计时和量化目前临床上无法检测到的妊娠应激源的“记录”，特别是在那些反映出最有问题的宫内环境和潜在最大的母婴风险的怀孕中。Platental Analytics，LLC建议基于数学(傅立叶分析)和物理学(统计热力学)中成熟的方法来优化整个胎盘形状的模型，这些方法基于从胎盘绒毛膜表面和切片的数字图像获得的数据，这些图像可以在任何医院使用数码相机和尖刀收集，并在具有孕产妇和新生儿结局的数据集中进行验证，这是将此类诊断工具推向市场之前必不可少的下一步。

DESCRIPTION (provided by applicant): The development of the placenta is a principal determinant of pregnancy outcome including prematurity, preeclampsia and fetal growth/ birth weight. In turn, next-pregnancy (maternal) risks as well as (newborn) risks of a wide variety of childhood and adult health outcomes have been reported to be predicted by pregnancy outcomes, with these outcomes serving as proxies for the adequacy (or not) of the intrauterine environment. We propose comprehensive measurement of the placental shape as a more direct assessment of the intrauterine environment, and have developed image analysis software tools for this task. Evidence suggests that major public health issues such as prematurity and preeclampsia have their origin in early gestation, in subclinical pathology that "sets the stage" for an irrevocable outcome. A growing body of epidemiologic evidence links placental growth to childhood and adult health outcomes, but these studies are limited to the traditional measures of placental weight and its derivatives (e.g. fetoplacental weight ratio) and have not reported consistent findings. The current "gold standard" measures of placental shape include dichotomous descriptions of placenta shape (as "round"/oval" and "irregular"), and take only a single pair of surface diameters, one thickness measure of the placental disk, and the distance of the cord insertion to the nearest disk edge. The most complex placental shapes, with off-center cords, irregular perimeters and variable disk thicknesses are those in which growth may have been most precarious during pregnancy; yet these most poorly measured by current "gold standards" may be the placentas most germane to the "fetal origins" debate and to understanding the genesis of disorders such as preeclampsia and prematurity that appear to have their roots in early pregnancy. Our recent work has demonstrated that: 1) abnormal placental shape is correlated with reduced placental efficiency and may be determined early in gestation; 2) different shapes appear to be "caused" by perturbations in placental development at different times in gestation; and 3) chorionic plate features measured by ultrasound at 11-14 weeks are significantly correlated to similar features observed at term. Our software tool takes the measurements of the delivered placenta and "rewinds the movie" to identify the timing and magnitude of a gestational stressor(s) that causes deviation(s) from "normal" placental growth. It more comprehensively captures complex placental shapes and vascular structures using digital .jpg photographs of placental chorionic surface and slices that can be prepared in any hospital with a digital camera and a sharp knife, and are detailed but still compact enough to be readily emailed to a central diagnostic facility for analysis. Such an approach promises to be reproducible across patients and institutions and valid. Another clinical use would be in pre-conceptual counseling and surveillance of subsequent pregnancies, as preeclampsia and prematurity can recur. The goals of this Phase 1 SBIR are to complete the development of our image analysis software tool and to validate it using a subsample of approximately 700 cases each from the Pregnancy, Infection and Nutrition Study of the University of North Carolina-Chapel Hill (UNC PIN) data set and 675 cases from the U.S. National Children's Study (NCS) Vanguard placental project. This proposal differs from our part of the NCS Formative Research Proposal in that this proposal is confined to developing software and modeling methods derived solely from (2D) digital images, while the NCS proposal is focused on studying the 3D shape obtained from a 3D scanner. PUBLIC HEALTH RELEVANCE: Complicated pregnancies of any type carry risks of recurrence in subsequent pregnancies as well as lifelong health risks for the child, but they most commonly occur in clinically "healthy" women. Deformed placental shapes can be, but are not currently, measured accurately and reliably at birth to serve as a "record" to identify, time and quantify what are currently undetectable clinically gestational stressors, especially in those pregnancies that reflect the most problematic intrauterine environments and potentially greatest maternal and/or infant risk. Placental Analytics, LLC, proposes to optimize models of whole placental shape based on well-established methodologies in mathematics (Fourier analysis) and physics (statistical thermodynamics) that are based on data derived from digital images of the placental chorionic surface and slices that could be collected in any hospital with a digital camera and a sharp knife, and validate them in data sets with maternal and newborn outcomes, the essential next step before bringing such diagnostic tools to market.