Title: First-trimester Placental Ultrasound Study (First PLUS): an observational cohort study to assess the clinical utility of the OxNNet Toolkit for the prediction of adverse pregnancy outcomes.
Funder: Department of Health and Social Care

Abstract: Background: Fetal growth restriction (FGR) is the single greatest cause of stillbirth. An effective first-trimester screening test would identify pregnancies at 'high-risk' thereby targeting NHS resources towards those at risk enabling delivery before stillbirth occurs. FGR can be predicted at 11-13 weeks' using placental volume and vascularity but no method is currently available to estimate these which can be used for population screening. Aims: We will use an observational cohort study to examine the clinical utility of the OxNNet Toolkit for the prediction of FGR and other adverse pregnancy outcomes in an unselected population presenting for routine first-trimester screening. Objectives: To assess the ability of the OxNNet Toolkit placental metrics to predict FGR and other adverse pregnancy outcomes at the routine first-trimester scan in an unselected cohort of women. To compare the performance of the OxNNet Toolkit metrics with the uterine artery blood flow (UtAD) for prediction of FGR and other adverse pregnancy outcomes. To develop fully automated quality control tools to improve the placental 3D-US acquisition. Work plan and methods: WP1: Undertake the First PLUS study to examine prediction of FGR using the OxNNet Toolkit placental metrics alone, and as part of a multi-factorial algorithm. WP2: Compare the performance of the OxNNet Toolkit vascular metrics with the previously used measurement of uterine artery blood flow. WP3: Develop an automatic quality-control system for the OxNNet Toolkit . Timelines for delivery: The project will take 2 years and we anticipate gaining CE marking within a year of completion. Anticipated Impact This falls under the remit of the NHSLTP and will produce two major value propositions: better pregnancy outcomes and significant cost-savings by preventing unnecessary imaging. Once validated, Perspectum will work with the AHSN, OUI and other imaging companies such as GE to rapidly deploy the OxNNet Toolkit into the NHS and beyond.

Lay abstract: Background: Every baby has an inherent growth potential which, with good maternal health and a well-functioning placenta, can usually be achieved. Failing to reach the appropriate size is called Fetal Growth Restriction (FGR ) and it can lead to a very poor outcome for the baby. FGR is the single most common cause of stillbirth, which devastates 8 families a day in the UK. It is also associated with pre-term birth and cerebral palsy. FGR is not currently preventable but spotting it early allows timely delivery which prevents the baby from dying before birth. Therefore, identifying pregnancies at high-risk of FGR should reduce stillbirth. FGR babies usually have abnormally small placentas at the time of the dating scan (c.11-13 weeks ). We have developed a method, the OxNNet Toolkit, that can provide reliable measurements of placental size in the first-trimester as well as estimating the blood flow within it. This will form the basis of a universal screening test for FGR. If we are able to identify women at high-risk of FGR early in pregnancy, we can also test potential new therapies which may actually prevent FGR from developing in the first place. As being born with FGR increases the risk of obesity, diabetes & cardiovascular disease in adulthood, any such treatment will have significant long-term health benefits in adulthood as well as preventing stillbirth. Aims: To assess the ability of the OxNNet Toolkit to predict FGR and other poor pregnancy outcomes (including pre-eclampsia). To improve the ultrasound acquisition and help sonographers learn the new technique in real-time. Work Plans: This builds on: A pre-existing artificial intelligence system which measures placental volume and blood flow from a simple 3D ultrasound (3D-US) scan (OxNNet Toolkit). Pilot data which shows the new measurements have the ability to predict FGR and pre-eclampsia. The work involves three steps: WP1. An observational study involving 4000 women (First PLUS) to explore the ability of the OxNNet Toolkit to predict FGR and other poor pregnancy outcomes. WP2. Comparing the performance of the OxNNet Toolkit blood flow measurements with the previously used, but sub-optimal, measurement of uterine artery blood flow. WP3. Developing a real-time automatic quality-control system for the OxNNet Toolkit to help sonographers collect high quality ultrasound scans. PPI: We have undertaken focus groups and have assurance that women feel this is a wanted and acceptable screening test. We have an advisory group made up of lay-people including women who have had FGR babies, (one is a co-applicant) and a dedicated PPI lead. Commercialisation: The tool has been patented and we are working closely with Oxford University, OUI and the AHSN to develop it. This study is needed for CE-Marking, a mandatory requirement before universal implementation is possible.

Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH