Objectives: To identify the variables that predict death/physiologic bronchopulmonary dysplasia (BPD) in preterm infants with severe respiratory failure.
Study Design: The study was a secondary analysis of data from the NICHD Neonatal Research Network trial of inhaled nitric oxide (iNO) in preterm infants. Stepwise logistic regression models and Classification and Regression Tree (CART) models were developed for the outcome of death or physiologic BPD ([O.sub.2] at 36 weeks post-menstrual age).
Result: Death and/or BPD was associated with lower birth weight, higher oxygen requirement, male gender, additional surfactant doses, higher oxygenation index and outborn status, but not the magnitude of response in Pa[O.sub.2] to iNO. The positive predictive value of the CART model was 82% at 95% sensitivity.
Conclusions: The major factors associated with death/BPD were an increased severity of respiratory failure, lower birth weight, male gender and outborn status, but not the magnitude of initial response to iNO. Journal of Perinatology (2008) 28, 420-426; doi:10.1038/jp.2008.18; published online 13 March 2008
Keywords: logistic models; predictive value of tests; ROC curve
Preterm infants with respiratory failure are at high risk of mortality or morbidity. Inhaled nitric oxide (iNO) may improve ventilation-perfusion mismatch and oxygenation, lower pulmonary arterial pressures, reduce lung inflammation, and thereby attenuate the pathophysiology of respiratory distress syndrome and bronchopulmonary dysplasia (BPD). The recent NICHD (National Institute of Child Health and Human Development) trial of iNO in preterm infants did not show a difference in the primary outcome of BPD or death between the control and the iNO groups. (1) However, post hoc analysis of data from this trial indicated that iNO may benefit very low birth weight infants with certain characteristics (birth weight > 1000 g) but may worsen outcome in other very low birth weight infants (for example, birth weight < 1000 g, on conventional ventilation). (1) Other recent trials of iNO in premature infants (2-4) indicate that iNO may benefit some premature infants, especially when used for longer durations. (4) To design new clinical observational and interventional studies, it is important to determine and identify clinical variables associated with a worse outcome. Previous small studies have indicated that a lack of initial response was predictive of death. (5) In the NICHD trial, response to study gas was defined by the change in Pa[O.sub.2] between baseline and 30 min of initiating iNO without any alterations in ventilator or oxygen settings. (1) A complete response was an increase of more than 20 mm Hg; a partial response, an increase of 10 to 20 mm Hg and no response, an increase of less than 10 mm Hg. However, the degree of response was arbitrarily defined, and it is possible that a different magnitude of response (for example, 30 or 40 mm Hg) may be associated with improved survival and a decreased incidence of BPD.
Classification and Regression Tree (CART) analysis is a statistical method that develops intuitive diagrams for identification of risk factors, prognosis or similar patterns in data. By recursive partitioning and automatic selection of optimal cut points...