The transition from a fetus to a newborn is one of the most complex and challenging transitions that all humans have to undertake. While most infants make this transition with remarkable ease, a significant number of infants require some form of intervention to survive. But unfortunately, this intervention can inadvertently injure the infant causing life-long disability. We believe that with a better understanding of the processes involved, it is possible to minimize the risk of injury. Our primary aim is to increase our understanding of the physiology underpinning the transition from fetal to newborn life and to use this information to improve the strategies used to support infants in the delivery room, during this vital stage of their life. The recent 2010 neonatal resuscitation guidelines proposed by ILCOR has highlighted many areas of neonatal resuscitation where specific recommendations lack appropriate evidence to support current or proposed practices. We will endeavor to fill some of these critical gaps in knowledge so that improvements in neonatal health care are based on sound scientific evidence. Our unique proposal will use large and small animal models to investigate the most critical issues experienced by preterm infants during their transition to newborn life at birth. We will: (I) identify the most effective ways of initiating ventilation in te delivery room. Specifically we will focus on procedures that optimize lung recruitment, facilitate the increase in pulmonary hemodynamics and protect the brain from hemodynamic instability. (II) determine how a sustained inflation, given as the first breath after birth in severely asphyxi preterm lambs, rapidly restores cardiac function and whether this rapid response increases the risk of brain injury (III) determine the physiological basis underlying respiratory, cardiovascular and cerebral vascular improvements observed in response to delayed umbilical cord clamping, and determine the factors that alter these physiological responses. Our application incorporates a unique collaboration between clinicians, physiologists, physicists and engineers and utilizes the most advanced physiological, imaging and analytical capabilities currently available. Underpinning this application is our unique imaging capabilities, which allow for real-time assessment of lung aeration with a temporal and spatial resolution capable of imaging the smallest air sacs throughout a breath. Analysis of these images (developed by us) allows for accurate determination of regional lung volume, lung perfusion and lung tissue motion. Our proposal is focused on addressing the major issues facing clinicians and providing a strong physiological basis to improve the treatment of premature infants during the transition to newborn life at birth.

Public Health Relevance

The transition from fetal to neonatal life is a major physiological challenge that every human must overcome to survive after birth. For many infants, particularly those born preterm, this transition can fail resulting in significant morbidiy or even mortality. Our research aims to improve the transition to newborn life in term and preterm infants, thus improving survivability and long-term outcomes for millions of infants'worldwide.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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Raju, Tonse N
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Monash University
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Lio, Alessandra; Aurilia, Claudia; Zahra, Valerie et al. (2018) Ventilation Prior to Umbilical Cord Clamping Improves Cardiovascular Stability and Oxygenation in Preterm Lambs After Exposure to Intrauterine Inflammation. Front Pediatr 6:286
Stojanovska, Vanesa; Atik, Anzari; Nitsos, Ilias et al. (2018) Effects of Intrauterine Inflammation on Cortical Gray Matter of Near-Term Lambs. Front Pediatr 6:145
Hooper, Stuart B; Crossley, Kelly J; Zahra, Valerie A et al. (2017) Effect of body position and ventilation on umbilical artery and venous blood flows during delayed umbilical cord clamping in preterm lambs. Arch Dis Child Fetal Neonatal Ed 102:F312-F319
Te Pas, Arjan B; Sobotka, Kristina; Hooper, Stuart B (2016) Novel Approaches to Neonatal Resuscitation and the Impact on Birth Asphyxia. Clin Perinatol 43:455-67
Ong, Tracey; Sobotka, Kristina S; Siew, Melissa L et al. (2016) The cardiovascular response to birth asphyxia is altered by the surrounding environment. Arch Dis Child Fetal Neonatal Ed :
Crawshaw, Jessica R; Hooper, Stuart B; Te Pas, Arjan B et al. (2016) Effect of betamethasone, surfactant, and positive end-expiratory pressures on lung aeration at birth in preterm rabbits. J Appl Physiol (1985) 121:750-759
Sobotka, Kristina S; Hooper, Stuart B; Crossley, Kelly J et al. (2016) Correction: Single Sustained Inflation followed by Ventilation Leads to Rapid Cardiorespiratory Recovery but Causes Cerebral Vascular Leakage in Asphyxiated Near-Term Lambs. PLoS One 11:e0156193
Polglase, Graeme R; Ong, Tracey; Hillman, Noah H (2016) Cardiovascular Alterations and Multiorgan Dysfunction After Birth Asphyxia. Clin Perinatol 43:469-83
Sobotka, Kristina S; Hooper, Stuart B; Crossley, Kelly J et al. (2016) Single Sustained Inflation followed by Ventilation Leads to Rapid Cardiorespiratory Recovery but Causes Cerebral Vascular Leakage in Asphyxiated Near-Term Lambs. PLoS One 11:e0146574
Hooper, Stuart B; Binder-Heschl, Corinna; Polglase, Graeme R et al. (2016) The timing of umbilical cord clamping at birth: physiological considerations. Matern Health Neonatol Perinatol 2:4

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