Improving Prematurity-Related Respiratory Outcomes at Vanderbilt

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.