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，据报道，下一次怀孕（产妇）风险以及各种儿童和成人健康结果的（新生儿）风险可以通过怀孕结果来预测，这些结果可以作为宫内环境是否充足（或不充足）的替代指标。我们建议全面测量胎盘形状，作为对宫内环境更直接的评估，并为此开发了图像分析软件工具。有证据表明，早产和先兆子痫等重大公共卫生问题起源于妊娠早期，其亚临床病理为不可挽回的结局“奠定了基础”。越来越多的流行病学证据将胎盘生长与儿童和成人的健康结果联系起来，但这些研究仅限于胎盘重量及其衍生物（例如胎胎盘重量比）的传统测量，并且没有报告一致的结果。目前衡量胎盘形状的“金标准”包括对胎盘形状的二分描述（如“圆形”/“椭圆形”和“不规则”），并且只采用一对表面直径，胎盘盘的一种厚度测量，以及脐带插入到最近盘边缘的距离。最复杂的胎盘形状，有偏离中心的脐带，不规则的周长和可变的盘厚，是那些在怀孕期间生长最不稳定的胎盘；然而，这些被目前的“金标准”衡量得最糟糕的胎盘，可能与“胎儿起源”的争论和理解诸如先兆子痫和早产等疾病的起源最密切相关，这些疾病似乎起源于早期妊娠。我们最近的工作表明：1)胎盘形状异常与胎盘效率降低有关，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) 11-14周超声测量的绒毛膜板特征与足月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“倒带电影”，以确定导致偏离“正常”胎盘生长的妊娠应激源的时间和大小。它更全面地捕捉复杂的胎盘形状和血管结构，使用胎盘绒毛膜表面和切片的数码jpg照片，可以在任何医院用数码相机和一把锋利的刀准备，这些照片细节详细，但仍然足够紧凑，可以随时通过电子邮件发送给中央诊断机构进行分析。这种方法有望在患者和机构之间重现，并且是有效的。另一个临床应用是孕前咨询和后续妊娠的监测，因为先兆子痫和早产可能会复发。第一阶段SBIR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（UNC PIN）妊娠、感染和营养研究（UNC PIN）数据集的约700例和来自美国国家儿童研究（NCS）先锋胎盘项目的675例的子样本对其进行验证。该提案与我们在NCS形成研究提案中的部分不同之处在于，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提案则侧重于研究从3D扫描仪获得的3D形状。

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.