Title: Optimal Oxygenation in Neonatal Lung Injury The current guidelines for neonatal resuscitation recommend the use of 21% oxygen during initial resuscitation of term newborn infants and use of blended supplemental oxygen to maintain target saturations to provide adequate oxygen while limiting damage from reactive oxygen radicals. The American Academy of Pediatrics recommends maintaining PaO2 between 50 and 80 mmHg in the management of sick neonates. These recommendations are based on studies using oxygen saturations in human infants and through translational studies in neonatal animal models without lung disease. Optimal oxygen concentration and target oxygen saturation range during resuscitation and ventilation of term neonates with lung injury/disease has been tested by this lab in term newborn lambs. SPO2 is not the sole determinant of oxygenation. When considering treatment that focuses on protecting brain function following birth with meconium aspiration/asphyxia, the same treatment may compromise pulmonary function. Transition to air breathing is a complex physiologic event, more so when there is significant lung disease. To further minimize the impact of oxygen damage we propose to study term lambs with lung injury induced by aspiration of meconium during gasping respirations as a consequence of umbilical cord occlusion and asphyxia (?asphyxia-MAS?). Limiting optimal target oxygen levels to two groups, 90-94% and 95-99% (that were found to be best treatment conditions during past studies) we propose to study 3 additional specific aims to improve both brain and lung function. The first specific aim will evaluate the hemoglobin level that optimizes cerebral O2 delivery and extraction, achieved by improving placental transfusion at birth using cord milking procedures that increase circulating fetal RBC?s.
The second aim will randomize the target PaCO2 and pH to provide the best cerebral blood flow while maintaining low pulmonary vascular resistance, continually managed by monitoring end-tidal CO2. The last specific aim will study the influence of hypothermia treatment currently used clinically following asphyxial birth to preserve brain function. Many factors can influence newborn clinical management of lung disease. We intend to clarify management criteria to better control the factors that influence hemodynamic measures of blood flow, pulmonary artery pressure and gas exchange to optimize oxygen delivery and extraction for both brain and lung function while limiting damage from oxygen free radicals.

Public Health Relevance

Title: Optimal Oxygenation in Neonatal Lung Injury Health relevance: Oxygen supplementation during resuscitation and subsequent ventilation of newborn infants with lung disease is a delicate balance between providing adequate tissue oxygen delivery and the damage from of free radicals that overwhelm their deficient antioxidant defense system. The studies to date have produced 24 manuscripts (see appendix) describing the effects of oxygen therapy during newborn ventilation; additional work is needed to further study the influences of hypothermia treatment or carbon dioxide and hemoglobin levels during this critical period. Results from the proposed studies are likely to influence guidelines for oxygen therapy during management of sick, term infants with lung disease.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
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Pregnancy and Neonatology Study Section (PN)
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Raju, Tonse N
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State University of New York at Buffalo
Schools of Medicine
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Chandrasekharan, P; Rawat, M; Reynolds, A M et al. (2018) Apnea, bradycardia and desaturation spells in premature infants: impact of a protocol for the duration of 'spell-free' observation on interprovider variability and readmission rates. J Perinatol 38:86-91
Chandrasekharan, Praveen; Rawat, Munmun; Gugino, Sylvia F et al. (2018) Effect of various inspired oxygen concentrations on pulmonary and systemic hemodynamics and oxygenation during resuscitation in a transitioning preterm model. Pediatr Res 84:743-750
Vali, Payam; Vento, Maximo; Underwood, Mark et al. (2018) Free radical damage can cause serious long-lasting effects. Acta Paediatr 107:2099
Lakshminrusimha, Satyan; Shankaran, Seetha; Laptook, Abbot et al. (2018) Pulmonary Hypertension Associated with Hypoxic-Ischemic Encephalopathy-Antecedent Characteristics and Comorbidities. J Pediatr 196:45-51.e3
Chandrasekharan, Praveen; Lakshminrusimha, Satyan (2017) The effectiveness of oral dextrose gel for the treatment of neonatal hypoglycaemia remains unclear. Evid Based Nurs 20:80-81
Chandrasekharan, P; Rawat, M; Lakshminrusimha, S (2017) Complications of prematurity: an infographic. J Perinatol 37:1185-1186
Katheria, A C; Lakshminrusimha, S; Rabe, H et al. (2017) Placental transfusion: a review. J Perinatol 37:105-111
Vali, Payam; Chandrasekharan, Praveen; Rawat, Munmun et al. (2017) Continuous Chest Compressions During Sustained Inflations in a Perinatal Asphyxial Cardiac Arrest Lamb Model. Pediatr Crit Care Med 18:e370-e377
Chandrasekharan, Praveen; Lakshminrusimha, Satyan (2017) Single dose of prophylactic oral dextrose gel reduces neonatal hypoglycaemia. Evid Based Med 22:62
Vali, Payam; Lakshminrusimha, Satyan (2017) The Fetus Can Teach Us: Oxygen and the Pulmonary Vasculature. Children (Basel) 4:

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