Prospective cohort study examines gene expressions related to hospital use in infants with bronchopulmonary dysplasia, suggesting predictive potential.
Background Bronchopulmonary dysplasia (BPD) is a chronic lung disease of prematurity caused by ventilator-related injury and impaired alveolar development, leading to persistent inflammation. It remains a major cause of neonatal morbidity and mortality and contributes to high healthcare utilization after discharge. Although infants with BPD frequently require rehospitalization, the molecular factors predicting hospital use remain unclear. Defining inflammatory transcriptomic profiles may improve early risk prediction and guide strategies to reduce long-term disease burden. Objective To determine whether differential expressions of inflammatory and epithelial stress-related genes measured at the first outpatient visit after discharge are associated with subsequent hospital utilization during the first year of life in infants with BPD. Methods We conducted a prospective cohort study of infants with a clinical diagnosis of BPD at the time of NICU discharge. Saliva samples were collected during the first outpatient follow-up visit for transcriptomic profiling using a targeted 590-gene panel focused on inflammation, immune signaling, and airway remodeling pathways (NanoString nCounter). Gene expression profiles were correlated with healthcare utilization outcomes within the first year of life, quantified as total days of care outside the home encompassing clinic visits, emergency department visits, and hospital readmissions. Associations between genes expressed above or below the cohort mean and cumulative hospitalization days were assessed using Fisher’s exact test. Results Among 27 infants with bronchopulmonary dysplasia, differential salivary gene expression revealed variable activation of inflammatory and epithelial pathways. Higher baseline expression of CXCL1 and DEFB103B at the first outpatient visit was associated with increased frequency of clinic and emergency department visits and hospital readmissions during the first year of life. Infants with elevated DEFB4A expression demonstrated a significantly greater number of total hospitalization days compared with those below the mean (p = 0.04). Although IL23A and CD97 showed nonsignificant trends toward higher expression in infants with prolonged hospitalizations, the overall pattern indicated a proinflammatory and antimicrobial gene signature linked to greater healthcare utilization. Conclusions Elevated expression of antimicrobial and proinflammatory genes, particularly DEFB4A, CXCL1, and DEFB103B, was associated with greater hospital utilization in infants with bronchopulmonary dysplasia. These findings suggest that persistent epithelial and innate immune activation contributes to ongoing disease activity and increased healthcare needs after discharge. Salivary transcriptomic profiling represents a promising, noninvasive approach for identifying infants at higher risk for rehospitalization and may help guide early interventions to reduce disease burden and improve long-term outcomes.
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Yassa et al. (2026) studied this question.
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