The goal of IMPROV is to identify molecular mechanisms that contribute to lung injury and long-term breathing problems in preterm infants by investigating two interrelated biochemical pathways: the urea cycle-nitric oxide pathway and the glutathione pathway. The investigators hypothesize that prematurity-related limitations in the function of these important biochemical pathways contribute to respiratory disease risk over the first year of life.

The primary goal of the IMPROV/PROP study is to identify biomarkers (biochemical, physiological and genetic) and clinical variables that are associated with and thus potentially predictive of pulmonary status in preterm infants at 1 year corrected age. IMPROV will test the hypothesis that biochemical immaturity and functional genetic variation in the urea cycle-nitric oxide (UC-NO) and glutathione (GSH) pathways influence the development and severity of bronchopulmonary dysplasia (BPD), a form of chronic lung disease that affects more than 10,000 premature infants each year in the US. IMPROV will also test the hypothesis that the duration and degree of NO insufficiency and free radical excess predicts BPD severity and correlates with persistence of lung problems after NICU discharge. Our hypothesis implicates (a) an immature liver and gastrointestinal ability to make citrulline and GSH, (b) inadequacy of nutritional amino acid substrate and (c) common genetic variations in the UC-NO and the GSH pathways in the pathogenesis of BPD. These factors limit the ability of the anatomically and functionally immature lung to respond to the physiologic and environmental stress of preterm birth. As part of the PROP multi-center study, novel approaches to characterizing lung status with non-invasive respiratory measures prior to NICU discharge will be employed. A composite primary outcome of morbidity that is based on serial parental reports of respiratory symptoms, medications, hospitalizations and dependence on technology during the first year of life has been developed.

Inclusion Criteria:

• Infants who are less than or equal to 7 days old;
• Gestational Age (GA) between 23 weeks and 0/7 days and 28 weeks and 6/7 days

Exclusion Criteria:

• The infant is not considered to be viable (decision made not to provide life-saving therapies);
• Congenital heart disease (not including PDA and hemodynamically insignificant VSD or ASD);
• Structural abnormalities of the upper airway, lungs or chest wall;
• Other congenital malformations or syndromes that adversely affect life expectancy or cardio-pulmonary development;
• Family is unlikely to be available for long-term follow-up.

Infants admitted to the Neonatal Intensive Care Unit who are < 29 weeks gestational age