Placental shape features, gestational timing and maternal and infant health

描述（由申请方提供）：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，下一次怀孕（母亲）的风险以及（新生儿）的各种各样的儿童和成人健康结果的风险已被报告预测怀孕的结果，这些结果作为代理的子宫内环境的充分性（或不）。我们建议全面测量胎盘的形状作为一个更直接的评估子宫内环境，并已开发图像分析软件工具，这项任务。 有证据表明，主要的公共卫生问题，如早产和先兆子痫有其起源于妊娠早期，在亚临床病理学，“设置阶段”的一个不可挽回的结果。越来越多的流行病学证据将胎盘生长与儿童和成人健康结果联系起来，但这些研究仅限于胎盘重量及其衍生物（例如胎儿胎盘重量比）的传统测量，并且没有报告一致的结果。目前胎盘形状的“金标准”测量包括对胎盘形状的二分描述（如“圆形”/椭圆形”和“不规则”），并且仅采用单对表面直径、胎盘盘的一个厚度测量以及脐带插入到最近的盘边缘的距离。最复杂的胎盘形状，偏离中心的线，不规则的周长和可变的盘厚度是那些在怀孕期间生长可能最不稳定的胎盘;然而，这些最不好用当前的“金标准”测量的胎盘可能与“胎儿起源”的争论最密切相关，并理解疾病的起源，如先兆子痫和早产，这些疾病似乎起源于妊娠早期。 我们最近的工作表明：1）异常的胎盘形状与胎盘效率降低相关，并可能在妊娠早期确定; 2）不同的形状似乎是由妊娠不同时期胎盘发育的扰动“引起”的; 3）在11-14周通过超声测量的绒毛板特征与足月时观察到的相似特征显著相关。 我们的软件工具对分娩的胎盘进行测量，并“倒带”，以确定导致偏离“正常”胎盘生长的妊娠应激源的时间和幅度。它使用胎盘绒毛膜表面的数字.jpg照片和切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用数码相机和锋利的刀制备，并且详细但仍然足够紧凑，可以通过电子邮件发送到中央诊断机构进行分析。这种方法有望在患者和机构中重现，并且有效。另一个临床用途是在怀孕前咨询和监测随后的怀孕，因为先兆子痫和早产可能复发。 本SBIR第1阶段的目标是完成我们的图像分析软件工具的开发，并使用来自北卡罗来纳大学教堂山分校（University of North Carolina-Chapel Hill）妊娠、感染和营养研究（Pregnancy，Infection and Nutrition Study）数据集的约700例子样本和来自美国国家儿童研究（NCS）Vanguard胎盘项目的675例子样本对其进行验证。 该提案与我们的NCS形成性研究提案部分不同，因为该提案仅限于开发仅来自（2D）数字图像的软件和建模方法，而NCS提案则专注于研究从3D扫描仪获得的3D形状。 公共卫生相关性：任何类型的复杂妊娠都有在随后的妊娠中复发的风险，以及对儿童终身健康的风险，但它们最常发生在临床上“健康”的妇女中。变形的胎盘形状可以，但目前还没有，在出生时准确和可靠地测量，作为一个“记录”，以确定，时间和量化目前无法检测的临床妊娠应激源，特别是在那些反映最有问题的宫内环境和潜在的最大的产妇和/或婴儿的风险。胎盘分析有限责任公司，提出了优化模型的整个胎盘形状的基础上完善的数学方法（傅立叶分析）和物理学（统计热力学），这些数据来自胎盘绒毛膜表面和切片的数字图像，这些图像可以在任何医院用数码相机和锋利的刀收集，并在数据集中验证它们与产妇和新生儿的结果，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.