Understanding Neonatal Transition – A Comprehensive Approach to Optimize Respiratory Care of Newborn Infants in the Delivery Room

• Applicant: Dr. Vincent Gaertner
• Subject Area: Pediatric and Adolescent Medicine ; Anatomy and Physiology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 547359845

Worldwide, more than 800,000 infants die annually from birth asphyxia after an inadequate transition, making it the most common reason for mortality below 5 years of age. However, the physiology of transition from a fluid-filled to an air-filled lung immediately after birth still remains poorly understood. Between 5 and 10 % of live born infants are born preterm. Almost all very preterm infants require respiratory support after birth by providing a positive end-expiratory pressure (PEEP) after birth in order to establish and maintain functional residual capacity (FRC) and to prevent hypoxemia. There are no meaningful clinical studies evaluating the effect of different pressure levels and recommendations are based on expert opinion only. Accordingly, PEEP levels vary largely between centres (between 5 to 20 cm H2O). The immediate postnatal stabilization is critical (so-called "Golden Hour") and failure to adequately aerate the lung may lead to mechanical ventilation and is consequently associated with death and relevant long-term neonatal morbidities. Thus, the right initial PEEP level during neonatal resuscitation is crucial but still unknown. Electrical impedance tomography (EIT) allows the real-time evaluation of intrapulmonary volume changes with a high temporal resolution and no radiation, making it the ideal tool to assess lung volumes of preterm and term infants. Lung inflammation is a crucial parameter in the cascade of lung injury and long-term pulmonary sequelae. Consequently, understanding the (sub-)cellular mechanisms promoting this cascade may help to improve future clinical management. In this proposal, we describe a six-year research programme where we aim (1) to understand the physiology of neonatal transition, (2) to improve the immediate clinical management of very preterm infants by performing a randomized controlled clinical trial on the effect of different pressure settings (high vs low), and (3) to link the knowledge about these interventions to preclinical (electro-)physiological as well as inflammatory data to define (patho-)physiological pathways and to inform future research direction. To do this, we will perform the following key studies: 1. Assess physiological mechanisms of lung aeration and pulmonary perfusion in term infants after birth; 2. Develop a patient-centered ranked outcome for use in neonatal trials; 3. Evaluate the effect of a higher vs lower distending pressure on patient-centered respiratory outcomes of very preterm infants - LEOPARD trial; 4. Assess mechanisms of lung aeration in preterm infants during physiological-based cord clamping (PBCC); 5. Evaluate effect of different pressure levels on lung aeration and ventilation distribution in very preterm infants; 6. Assess effect of different pressure levels on proteome profiles and inflammatory markers in very preterm infants; 7. Establish a sustainable newborn research center after the current funding period.

• DFG Programme: Emmy Noether Independent Junior Research Groups