Effect of hyperoxia and mechanical ventilation on premature infants

Abstract

Mechanical ventilation with hyperoxia is often needed to treat premature infants with immature lungs However mechanical ventilation inevitably damages the lungs and causes bronchopulmonary dysplasia (BPD) in some premature infants BPD is characterized by larger and fewer alveoli due to impaired lung development and usually requires prolonged respiratory support The possible contributing factors of BPD include oxygen toxicity mechanical ventilation perinatal infection/inflammation and immaturity of the lungs To investigate the contribution of oxygen toxicity to BPD the first study was to analyze the mechanism underlying hyperoxia-induced lung injury We found that hyperoxia inhibited proliferation and induced cell cycle arrest in A549 pulmonary epithelial cells Interestingly hyperoxia induced not only necrotic cell death but also an autophagic response in A549 cells Moreover hyperoxia increased intracellular reactive oxygen species and altered mitochondrial membrane potential The antioxidant N-acetyl-L-cysteine attenuated hyperoxia-induced cell death in A549 cells Finally the hyperoxia-induced autophagic response was confirmed in a neonatal rat model of acute lung injury If autophagy is a prosurvival response of cells under stress our findings may have clinical implications for the development of protective strategies against hyperoxia-induced injury in the developing lung such as BPD in the premature infants Many studies have pointed out that BPD is associated with poorer neurodevelopmental outcomes To explore the underlying mechanism of BPD that may contribute to the neurodevelopmental impairment in premature infants the second study which used a large nationwide database investigated in a 10-year retrospective follow-up the association between the duration of mechanical ventilation and the risk for various developmental disorders in extremely low birth weight (ELBW) (<1 000 g) infants born between 1998 and 2001 Seven hundred twenty-eight ELBW infants without diagnoses of brain insults or focal brain lesions in the initial hospital stay were identified and divided into three groups (days on ventilator: ≦ 2 3-14 ≧ 15 days) After adjusting for demographic and medical factors the infants in the ≧ 15 days group had higher risks for cerebral palsy (CP) (adjusted hazard ratio: 2 66; 95% confidence interval: 1 50-4 59; p <0 001) and attention-deficit/hyperactivity disorder (ADHD) (adjusted hazard ratio: 1 95; 95% confidence interval: 1 02-3 76; p <0 05) than did infants in the ≦ 2 days group The risk for autism spectrum disorder (ASD) or intellectual disability (ID) was not significantly different between the three groups We conclude that mechanical ventilation for ≧ 15 days increased the risk for CP and ADHD in ELBW infants even without significant neonatal brain damage Developing a brain-protective respiratory support strategy in response to real-time cerebral hemodynamic and oxygenation changes has the potential to improve neurodevelopmental outcomes in ELBW infants

Date of Award	2014 Aug 24
Original language	English
Supervisor	Wen-Tsan Chang (Supervisor)