Intrapulmonary Administration of Vitamin A to improve Respiratory Outcomes of extremely preterm infants (IAVARO study)
Preterm infants are born with underdeveloped lungs. Breathing support in the form of mechanical ventilation and additional oxygen is life saving for these infants. However, mechanical ventilation may also contribute to the lung inflammation and interruption of lung growth leading to Bronchopulmonary Dysplasia (BPD). BPD affects 40 % of extremely preterm (born before 28 week gestational age) infants. This disease is one of the conditions that can predict long-term outcomes.
Vitamin A is required for normal lung growth. It may protect lung from the damage caused by additional oxygen and mechanical ventilation. Clinical studies have shown that it decreases the risk of BPD. However, a major limitation in its routine use is its poor enteral absorption. Intravenous administration of vitamin A has limitations while intramuscular route although effective, subjects infants to the discomfort and risk of repetitive muscular trauma.
My research aims to investigate a convenient and effective route of administration of vitamin A to the extremely preterm infants to improve respiratory outcomes. The routes of administration under investigation will be a) intratracheal instillation with surfactant, and b) inhalation of aerosolised vitamin A. I expect that local rather than systemic administration will decrease systemic adverse effects.
My research work will involve a) laboratory experiments to investigate physical properties of surfactant when mixed with vitamin A, and optimum method of delivery of inhaled vitamin A; b) animal experiments to investigate effects of local Vitamin A administration on gas exchange; and c) a clinical study to investigate beneficial effect on BPD and other respiratory outcomes.
If found effective, intratracheal instillation and inhalation of vitamin A will avoid painful injections in the “tiny” premature infants. It may also decrease systemic toxicity because of the targeted drug delivery.
Why my research is important
BPD is an important complication and major cause of persistent breathing disorders in infants born prematurely. BPD remains a significant problem despite major advances in the treatment of preterm infants over the last 2 decades. Infants with BPD have abnormal lung function in adult life and are at risk of adverse long term neurodevelopment. Therefore additional effective therapy is urgently required.
Vitamin A therapy is effective in reducing the risk of BPD, but has achieved limited uptake due to the low acceptance of the need for repeated intramuscular injections. Vitamin A therapy will be accepted more widely if a suitable and effective method of administration to the target organ (lung) is devised. This project aims to investigate a suitable and effective route of vitamin A administration to improve respiratory outcomes in extremely preterm infants. If intratracheal instillation and inhalation methods of vitamin A administration prove beneficial for bronchopulmonary dysplasia it may benefit an estimated 75 thousand extremely preterm infants born each year worldwide.