Impact of Bronchopulmonary Dysplasia on Early Life Respiratory Morbidity in Children with Respiratory Distress Syndrome: A Nationwide Population-Based Study

Background: Bronchopulmonary dysplasia (BPD) can cause respiratory morbidity beyond the neonatal period. We aimed to analyze the influence of BPD on childhood lower respiratory illness (LRI) and asthma among patients diagnosed with neonatal respiratory distress syndrome (RDS). Methods: This case–control study analyzed data of children born between 2002 and 2015 retrieved from a nationwide database. We included 55066 children diagnosed with RDS. Patients with major congenital anomalies or who died during the initial admission period were excluded. The main outcomes were 2-year childhood LRI and asthma at ages 3 and 5. Findings: Readmission for LRIs within 2 years of birth occurred in 53·9% and 37·9% of the BPD (n=9470) and non-BPD (n=45596) cases, respectively. In the BPD group, the median number of hospitalizations was significantly higher (2 [1–40] vs. 1 [1–29], p<0·001), hospital stay duration was significantly longer (13 [6–30] vs. 8 [5–15] days, p<0·001), mechanical ventilation (3·9% vs. 0·5%, p<0·001) and oxygen use (41·0% vs. 14·5%, p<0·001) rates were significantly higher than in the non-BPD group. The relative risk of BPD was 1.42 (95% CI, 1·39–1·45) on total readmission and 6·53 (95% CI, 5·96–7·15) on intensive care unit readmission, consistent with the subgroup analysis of very low birth weight population. Asthma prevalence in the BPD group was significantly higher (57·6% vs. 48·9% at age 3 and 44·3% vs. 38.2% at age 5, p<0·001) than in the non-BPD group, and three times higher than in the general population. Interpretation: In children with RDS, BPD could affect repetitive, prolonged, and worse LRI as an independent risk factor for respiratory morbidity during the first 2 years of life. BPD was also a crucial risk factor for asthma in preschoolers. Funding: This study was supported by a Severance Hospital Research fund for Clinical excellence (SHRC) (C-2020-0014). Declaration of Interest: All authors have no conflict of interest. Ethical Approval: This study protocol was reviewed and approved by the Institutional Review Board of Severance Hospital (approval No. 4-2019-0383). As this was an observational study without intervention and the presentation of any identifying data, the requirement for informed consent was waived.