DESCRIPTION (provided by applicant): Mounting evidence suggests that abnormal placental development in early gestation is highly associated with many maternal and fetal pathologic conditions, which can manifest later in pregnancy. The ability to evaluate in real time human placental structure and function in early gestation by using novel ultrasound tools will allow for the identification of early markers of placental dysfunction with the ultimate long- term goal of prevention of adverse pregnancy outcomes. As initial steps in accomplishing this long-term goal, we propose this study designed to find which of the novel ultrasound tools are best at discriminating between women who will develop adverse pregnancy outcomes and those who will not. We have formed collaboration with Toshiba Medical Systems, one of the ultrasound industry leaders, that is focused on evaluating recently developed novel ultrasound tools that substantially expand our ability to study placental structure and function in vivo. This collaboration will advance the field through technology development and translational research. Our collaboration brings together novel tools, strong technological expertise, leadership in obstetrical ultrasound, and a track record of clinical research. The novel ultrasound tools that will be used in our study include Superb Micro-Vascular Imaging (SMI) for the comprehensive assessment of placental microvasculature, Shear Wave Elastography (SWE) for the evaluation of placental tissue stiffness and MicroPure(r) for the visualization of placental microcalcificatios content. We plan to apply these novel ultrasound tools, along with fetal and placental biometric and 3D ultrasound measurements, on a control group of normal pregnancies and a study group of at-risk pregnancies starting from early gestation and in a longitudinal cohort design. Maternal and neonatal outcome will be collected along with storage of biospecimen and placental pathology for future evaluation. Pregnancy ending at less than 37 0/7 weeks' gestation for any cause will be the primary study outcome and will differentiate normal from abnormal pregnancy. The ultrasound data will be analyzed to identify significant early markers of placental dysfunction. We have 3 study aims. First is to develop longitudinal nomograms for the novel ultrasound tools in normal human pregnancies. Second is to apply these novel ultrasound tools to study placental development in at-risk human pregnancies. Third to develop and evaluate an overall novel placental ultrasound marker: "The Placental Index" as an early gestation, non-invasive, marker of placental dysfunction for the prediction of adverse human pregnancy outcomes.

PUBLIC HEALTH RELEVANCE Project Narrative: The abnormal development of the placenta in early pregnancy is highly associated with poor outcome for the mother and child. We are applying novel ultrasound tools on the placenta to predict this poor outcome from early pregnancy. Once we are able to predict these at-risk pregnancies, we can then provide treatment that can improve outcome for mother and child.