| Respiratory instability is common in premature infants. Immature development of lung structures, incomplete ossification of the ribs, and underlying pulmonary disease all contribute to distortion of the chest wall during respiration. This places the infant at a respiratory disadvantage, as the energy expenditure of the diaphragm must combat rib cage distortion in addition to contributing to air exchange. This respiratory inefficiency places a high burden on the premature infant. If the burden exceeds the diaphragm's contractile capabilities then respiratory instability will result.;Currently, there is evidence that specific amino acids support the function of the diaphragm. Animal studies have shown that the branched-chain amino acids are highly used by the diaphragm---both for accretion of muscle tissue and for energy production to support muscle contraction. Pulmonary response studies in both newborn animals and premature human infants have demonstrated improved respiratory function following short-term branched-chain amino acid enrichment.;This doctoral project investigated the respiratory response of premature infants receiving branched-chain amino acid supplementation for longer periods and developed a model based on the contribution of the diaphragm to respiratory stability. Three studies were conducted as part of this project. The first, established the test-retest reliability of respiratory inductive plethysmography---a technique used to evaluate patterns of respiration. Intraclass correlation analysis revealed repeatability values ranging from 44--75% for thoraco-abdominal synchrony, respiratory pause, and timing events in eight premature infants over three consecutive days. The results of this study established respiratory inductive plethysmography as a suitable technique to measure respiratory stability in premature infants. The second study, documented average plasma amino acid concentrations in infants consuming seven different diets via a meta-analysis of 56 studies. This study confirmed that blood amino acid concentrations are influenced by diet and established average values for individual amino acids. The third study investigated changes in respiratory stability in premature infants consuming two parenteral regimes differing in branched-chain amino acid content---one containing 30% which is typical for infant parenteral nutrition and one enriched to 53%. This study was a double-blind clinical trial with each infant serving as own control (thirteen infants were enrolled, six completed the study). Following the enriched phase, the infants demonstrated less respiratory pause (23 fewer breathing cessation events per hour), improvements in breathing coordination (9.0% less thoraco-abdominal asynchrony), and alterations in timing events that have been associated with defense of lung volume.;We conclude that branched-chain amino acid enrichment stabilizes respiratory function in premature infants. In addition, we propose (based on our work and the work of others) that the diaphragm contributes to the improved respiratory response seen in premature infants due to the preferential use of the branched-chain amino acids by that muscle. |
