Abstract
We need a better risk stratification system for the increasing number of survivors of extreme prematurity suffering the most severe forms of bronchopulmonary dysplasia (BPD). However, there is still a paucity of studies providing scientific evidence to guide future updates of BPD severity definitions. Our goal was to validate a new predictive model for BPD severity that incorporates respiratory assessments beyond 36 weeks postmenstrual age (PMA). We hypothesized that this approach improves BPD risk assessment, particularly in extremely premature infants. This is a longitudinal cohort of premature infants (≤32 weeks PMA, n = 188; Washington D.C). We performed receiver operating characteristic analysis to define optimal BPD severity levels using the duration of supplementary O2 as predictor and respiratory hospitalization after discharge as outcome. Internal validation included lung X-ray imaging and phenotypical characterization of BPD severity levels. External validation was conducted in an independent longitudinal cohort of premature infants (≤36 weeks PMA, n = 130; Bogota). We found that incorporating the total number of days requiring O2 (without restricting at 36 weeks PMA) improved the prediction of respiratory outcomes according to BPD severity. In addition, we defined a new severity category (level IV) with prolonged exposure to supplemental O2 (≥120 days) that has the highest risk of respiratory hospitalizations after discharge. We confirmed these findings in our validation cohort using ambulatory determination of O2 requirements. In conclusion, a new predictive model for BPD severity that incorporates respiratory assessments beyond 36 weeks improves risk stratification and should be considered when updating current BPD severity definitions.
Highlights
We need a better risk stratification system for the increasing number of survivors of extreme prematurity suffering the most severe forms of bronchopulmonary dysplasia (BPD)
We hypothesized that including the total number of days requiring O2 in BPD severity definitions will: 1) improve the prediction of respiratory outcomes according to BPD severity, and 2) define a new severity category that encompasses babies born extremely premature with prolonged O2 exposure
We found that the total number of days requiring supplemental O2 was the best predictor for our primary BPD severity classifier (AUC = 0.734)
Summary
We need a better risk stratification system for the increasing number of survivors of extreme prematurity suffering the most severe forms of bronchopulmonary dysplasia (BPD). We hypothesized that including the total number of days requiring O2 (without restricting at 36 weeks PMA) in BPD severity definitions will: 1) improve the prediction of respiratory outcomes according to BPD severity, and 2) define a new severity category (level IV) that encompasses babies born extremely premature with prolonged O2 exposure To test these hypotheses we used a data-driven approach to construct a new BPD severity classification in four steps: 1) determination of the optimal discrimination thresholds of the days of O2 requirement to predict respiratory hospitalization after NICU discharge (primary classifier of BPD severity) using receiver operating characteristic (ROC) analysis in a cohort of premature infants (n = 188; Washington D.C. discovery cohort); 2) validation of the new clinical BPD severity scale using lung X-ray scoring as independent secondary marker of BPD severity in the same study cohort; 3) characterization of the resultant clusters of BPD severity using individual clinical features and formal statistical testing between groups; and 4) testing the new predictive risk model for premature infants that incorporates the total number of O2 dependence days beyond 36 weeks PMA in an independent cohort with longitudinal data covering 12 months after NICU discharge (n = 130; Bogota, Colombia, validation cohort). We are defining new BPD subsets of severity, which may be crucial to investigate disease mechanisms and to evaluate future interventions in clinical trials
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