Placental shape features, gestational timing and maternal and infant health

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 ofa 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 shapesand 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.