Identification of mechanical ventilation-related risk factors for retinopathy of prematurity in preterm infants

Background: Retinopathy of prematurity (ROP) remains a leading cause of preventable childhood blindness. While gestational age (GA) and oxygen therapy are established risk factors, prior research has largely treated oxygen exposure as an aggregate variable, without disaggregating the impact of specific respiratory support modalities. This study investigated whether the mode and duration of respiratory support independently influence ROP risk.

Methods: We conducted a single-center retrospective cohort study of 83 preterm infants (GA <28 weeks) admitted to the neonatal intensive care unit (NICU) at Jeonbuk National University Hospital (2014–2024). Modality-specific durations [conventional ventilation, high-frequency oscillatory ventilation (HFOV), non-invasive neurally adjusted ventilatory assist (NIV-NAVA), nasal continuous positive airway pressure (NCPAP), and high-flow nasal cannula (HFNC)] and time-weighted average (TWA) ventilator settings [fraction of inspired oxygen (FiO₂), mean airway pressure (MAP), positive end-expiratory pressure (PEEP), and peak inspiratory pressure (PIP)] at postnatal days 1, 3, 7, and 10 were extracted from continuous electronic medical records (EMRs). Associations with ROP were evaluated using Firth’s penalized logistic regression, with and without GA adjustment.

Results: ROP was diagnosed in 52 infants (62.7%). In unadjusted analyses, GA [odds ratio (OR) =0.54; 95% confidence interval (CI): 0.35–0.80; P<0.001] and NCPAP duration (OR =1.04; 95% CI: 1.01–1.09; P=0.01) were significantly associated with ROP, alongside TWA PEEP on days 7 and 10. After GA adjustment, NCPAP duration remained the sole independently associated variable (OR =1.04; 95% CI: 1.00–1.08; P=0.04). No other modality, TWA parameter (including FiO₂), or respiratory severity index showed an independent association after adjustment for GA.

Conclusions: NCPAP duration is independently associated with ROP in infants born before 28 weeks, with each additional day associated with a 4% increase in risk after adjustment for GA. This association was independent of mean FiO₂, suggesting that oxygenation variability during spontaneous breathing may be a more proximal pathophysiological driver; however, as oxygen saturation (SpO₂) variability was not directly measured, this interpretation should be regarded as hypothesis-generating. NCPAP duration may serve as a practical EMR-derived metric for ROP risk stratification in the NICU.