Thesis: Influence of the in utero environment on diaphragm structure and function
Despite major advances in neonatal care over the last 2 decades, preterm birth is the leading cause of perinatal morbidity and mortality in developed countries. The incidence of respiratory distress syndrome (RDS) is higher among human infants who are born prematurely and the incidence increases with decreasing gestation. A functional diaphragm is critically important to the successful establishment of unsupported spontaneous breathing. We hypothesized that the mechanism for diaphragm failure after birth is related to increased mechanical load on the diaphragm in preterm babies. Thus, the integrity of the diaphragm muscle at birth may critically influence the development of respiratory failure after birth.
Inflammation is linked to more than 70% of very preterm births and up to 90 % of preterm infants less than 34 weeks gestation are exposed to glucocorticoids on at least one, and sometimes multiple occasions prior to delivery. My PhD aims to determine the effect of common, clinically relevant antenatal exposures (inflammation, glucocorticoids) and the timing of these insults on the metabolic, functional and structural phenotype of the fetal and newborn diaphragm. In addition, potential treatments to ameliorate the severity of diaphragm dysfunction that contributes to respiratory failure will be investigated.
Why my research is important
Each year more than 25000 infants in Australia and New Zealand and over 15 million infants worldwide are born pre-term. The incidence of respiratory failure following preterm birth is higher than at any other time of life and is associated with significant mortality and long term morbidity. This study will systematically examine the effect of antenatal exposures on diaphragm integrity and enhance our understanding of factors contributing to early onset diaphragmatic dysfunction. The outcomes of this research have the potential to significantly reduce the respiratory morbidity and mortality associated with preterm birth and to promote a healthier start to life.