BackgroundAggressive retinopathy of prematurity (A-ROP) poses a significant risk for visual impairment in preterm neonates, including those considered at low risk for ROP. Nonetheless, factors influencing A-ROP occurrence in low-risk preterm neonates remain underexplored. We aimed to identify oxygen therapy-related factors associated with A-ROP in this population.MethodsThis retrospective case-control study included low-risk preterm neonates (gestational age >= 30 weeks and birth weight >= 1 kg) treated for ROP between January 2005 and May 2023 at two Korean hospitals. Patients were divided into A-ROP and staged ROP groups, and oxygen therapy-related factors were analyzed using logistic regression.ResultsOf the 99 neonates included, 72% were diagnosed with A-ROP. No significant between-group differences were observed in the total duration of oxygen therapy or its delivery methods, except for non-invasive positive ventilation. Mean partial pressure of oxygen (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.89-0.99) and its fluctuation (OR, 1.09; 95% CI, 1.03-1.15) were significant risk factors for A-ROP, with cutoff values of <52.8% and >82.3%, respectively.ConclusionMaintaining stable oxygen levels while avoiding hypoxia may help reduce the risk for A-ROP in low-risk neonates requiring ROP treatment. These findings may help refine oxygen therapy guidelines in neonatal care to improve A-ROP prevention in this population.Impact StatementAggressive retinopathy of prematurity (A-ROP) can significantly threaten vision, even in preterm neonates considered at low risk for ROP.The contributing factors to A-ROP in this low-risk population have been insufficiently investigated.This study is the first to identify peripheral oxygen levels and their fluctuations as significant factors associated with A-ROP development in low-risk preterm neonates requiring treatment.These findings highlight the importance of maintaining stable oxygenation and preventing hypoxia to reduce the risk of A-ROP in this population.