This Pathfinder project will establish a radical change in the treatment of newborns using an artificial placenta (ArtPlac). What drives us towards a radical new treatment approach? 2 mio. neonatal deaths that occur worldwide yearly. The technological advancements of the last fifty years were based on scaling down adult devices which are not ideal for all babies. Why? Because babies are not just small adults! In fact, the applied treatments are very invasive and cause side effects by damaging their sensitive bodies. Survivors often suffer from life-long complications or cannot live independently. In utero, the placenta is a life-giving organ and serves as fetal lung, fetal kidney, and feeder. Because the placenta cannot be reconnected after preterm birth, we aim to continue the placental support with ArtPlac. Our novel device simply connects to the belly button for lung and kidney support while the newborn can breathe, mature, and heal. To achieve this, a novel compact and miniaturized all-in-one artificial placenta device combining lung and kidney functions will be developed. Our plug-in approach will use the natural umbilical vessels at the belly button with expandable catheters to provide a large bore vascular access like in utero. This allows ArtPlac to be driven solely by the newborn's heart like in the womb. Inline sensors will analyze blood parameters without painful collection. Feedback loops in ArtPlac will provide individual demand-driven support. Inbuilt features for hemocompatibility will prevent thrombosis and use of high-dose systemic anticoagulation with the high risk for brain bleeding. Importantly, ArtPlac allows family integrated care providing a therapy for the newborn in close connection to its family. In summary, our visionary approach revolutionizes the treatment of newborns after birth. It will reduce brain damage and comorbidities, promote long-term health, and therefore improve the survival chances of up to 1.2 mio. newborns per year.

The UPRISE project aims to unravel the complex mechanisms by which air pollution, in particular ultrafine particles (UFPs) and micro-nanoplastics (MNPs), disrupt normal fetal development leading to an increased risk of adverse birth outcomes (ABOs), including preterm birth, increasing the risk of premature children to develop a range of non-communicable diseases (NCDs) in adulthood. UPRISE will develop exposure databases and assessment models for these emerging pollutants in different exposure scenarios to improve our understanding of their sources, concentrations and dispersion patterns. UPRISE will include a clinical study with pregnant participants exposed to different levels of UFPs and MNPs pollution to analyse possible modes of action leading to ABO based on transcriptomic, epigenetic or mitochondrial mutation analysis and subsequently identify possible key events, including molecular initiating events. As a result, causal models supported by weight-of-evidence analysis will be developed to demonstrate the link between contaminant uptake and events triggering the ABO of interest. To facilitate the dissemination of results and their application in policy-making, UPRISE will develop user-friendly tools for reporting and sharing data, with the aim of facilitating the integration of scientific evidence into the updating of European and national air quality standards. By advancing in the quantification of the public health impact of prenatal air pollution exposure and providing guidelines and decision support tools for policy makers, the project will contribute to reducing the burden of NCDs associated with preterm birth and other ABOs.

Very preterm birth is a principal determinant of motor and cognitive impairment in later life. About 50 000 infants in the EU survive very preterm birth annually and are at much higher risk of cerebral palsy, visual and auditory deficits, impaired cognitive ability, psychiatric disorders and behavioural problems than infants born at term. However, the long term prognosis at initial discharge from hospital for each individual infant is unknown. Follow-up screening and prevention programmes aim to identify health problems early, enable interventions to improve outcome and to allow optimal management of health care. Despite the recognised importance of these programmes, little is known about their actual application and impact. These programmes consume significant resources because of the multidisciplinary staff required for clinical and developmental assessments and interventions, the coordination required to maintain contact with children after discharge and the time input from families. This project uses a unique resource – the EPICE cohort of 6675 babies born before 32 weeks of gestational age and surviving to discharge home in 18 geographically diverse regions in 2011/2012 – to assess the impact of these screening programmes on health, care and quality of life for very preterm infants and their families as well as on coverage, ability to meet needs, health equity and costs at the population-level. It will also generate new knowledge about assessment tools and methods. Four inter-related studies will be carried out in 11 EU countries by a multi-disciplinary consortium of clinicians (in obstetrics, paediatrics, and child development), researchers (in epidemiology, health services research and health economics) and a user organisation. Partners have the expertise to implement this project and the national and international renown to translate its result into better programmes and policies.

This project will provide new knowledge regarding the best regimen, timing, dose, and route of administration of human mesenchymal stem cells (H-MSC) for regenerating the brain damage in infants born preterm; born before 37 of a typical 40 weeks of gestation. Over 15 million babies are born preterm every year it is a leading cause of death and permanent disability, often due to brain damage. The H-MSC that we will comprehensively screen are FDA-approved and in the process of being produced in a GMP grade, making them suitable for future clinical trials in human preterm born infants. These H-MSC will be evaluated in a large number of rodent models mimicking the key insults and brain damage observed in human preterm infants who will develop later motor, cognitive, and behavioral deficits. We will also apply theseH-MSC in two sheep models of injury relevant to brain damage associated with preterm birth. These large animal trials are a key step before initiating clinical trials in this high risk human population. Additional Workpackages will address the mechanisms underlying the regenerative effects of these H-MSC. This project addresses the call text by value adding to current knowledge of stem cell types and applying it to a large patient group with an unmet clinical need – infants with encephalopathy of the preterm born infant. Steps on the innovation chain targeted – preclinical research, proof of concept and to a lesser degree characterization of regenerative mechanisms.