Bronchopulmonary Dysplasia and Perinatal Characteristics Predict 1-Year Respiratory Outcomes in Newborns Born at Extremely Low Gestational Age: A Prospective Cohort Study

Abstract

Objective: To assess the utility of clinical predictors of persistent respiratory morbidity in extremely low gestational age newborns (ELGANs).

Study design: We enrolled ELGANs (<29 weeks' gestation) at ≤7 postnatal days and collected antenatal and neonatal clinical data through 36 weeks' postmenstrual age. We surveyed caregivers at 3, 6, 9, and 12 months' corrected age to identify postdischarge respiratory morbidity, defined as hospitalization, home support (oxygen, tracheostomy, ventilation), medications, or symptoms (cough/wheeze). Infants were classified as having postprematurity respiratory disease (PRD, the primary study outcome) if respiratory morbidity persisted over ≥2 questionnaires. Infants were classified with severe respiratory morbidity if there were multiple hospitalizations, exposure to systemic steroids or pulmonary vasodilators, home oxygen after 3 months or mechanical ventilation, or symptoms despite inhaled corticosteroids. Mixed-effects models generated with data available at 1 day (perinatal) and 36 weeks' postmenstrual age were assessed for predictive accuracy.

Results: Of 724 infants (918 ± 234 g, 26.7 ± 1.4 weeks' gestational age) classified for the primary outcome, 68.6% had PRD; 245 of 704 (34.8%) were classified as severe. Male sex, intrauterine growth restriction, maternal smoking, race/ethnicity, intubation at birth, and public insurance were retained in perinatal and 36-week models for both PRD and respiratory morbidity severity. The perinatal model accurately predicted PRD (c-statistic 0.858). Neither the 36-week model nor the addition of bronchopulmonary dysplasia to the perinatal model improved accuracy (0.856, 0.860); c-statistic for BPD alone was 0.907.

Conclusion: Both bronchopulmonary dysplasia and perinatal clinical data accurately identify ELGANs at risk for persistent and severe respiratory morbidity at 1 year.

Trial registration: ClinicalTrials.gov: NCT01435187.

Keywords: prematurity; pulmonary morbidity; wheeze.

Figure 2

Accuracy of perinatal (including only factors identified in the first day of life) and 36-week (including perinatal variables and variables describing infant status through 36 weeks’ post-menstrual age or discharge) multivariate models for post-prematurity respiratory disease (PRD) and respiratory morbidity severity (RMS). A. Receiver operator characteristic curves, generated by plotting sensitivity versus 1-specificity, for prediction of PRD. Area under the curve, for various PRD models: perinatal (0.858), 36-week (0.856), perinatal with the addition of BPD (0.860), and BPD-alone (0.907). BPD was classified as No/Mild, Moderate, or Severe. B-E. Predicted probability of outcome for respiratory morbidity severity (RMS) from multivariate models versus observed level of RMS classification. B. Probability of mild-to-severe (versus minimal/none) RMS classification for perinatal model. C. Probability of severe (versus not severe) RMS classification for perinatal model. D. Probability of mild-to-severe (versus minimal/none) RMS classification for 36-week model. E. Probability of severe (versus not severe) RMS classification for 36-week model.