Clinical exposure thresholds associated with retinopathy of prematurity in preterm infants born at high altitude

This study characterizes clinical and hematologic risk factors for retinopathy of prematurity (ROP) among preterm infants born at high altitude, where chronic environmental hypoxia represents a relevant physiological stressor but cannot be evaluated as an independent causal determinant. A retrospective cohort study was conducted in a tertiary neonatal intensive care unit located at 2240 m above sea level (Mexico City). Preterm infants with gestational age < 35 weeks and birthweight < 2000 g were included. Exclusion criteria were major congenital anomalies, death prior to ophthalmologic screening, and incomplete clinical data. Associations between clinical variables and ROP were assessed using univariate and multivariate logistic regression. Receiver operating characteristic (ROC) analyses were performed to identify cohort-specific exposure thresholds for respiratory support and transfusion burden. Among 76 infants, 22 (28.9%) developed ROP of any stage. Compared with infants without ROP, affected infants required longer supplemental oxygen therapy (median 42.5 vs. 20.0 days, p = 0.001), prolonged mechanical ventilation (17.0 vs. 5.0 days, p = 0.008), and more blood transfusions (6.0 vs. 2.0, p = 0.007). After reclassification, the incidence of necrotizing enterocolitis did not differ significantly between infants with and without ROP and was therefore retained only as a descriptive variable. Multivariate regression confirmed duration of oxygen exposure and transfusion burden as independent predictors of ROP. ROC analyses identified exposure thresholds associated with increased ROP risk: ≥ 35 days of oxygen therapy, ≥ 12 days of mechanical ventilation, and ≥ 6 transfusions. Preterm infants born and treated at high altitude exhibit clinically relevant associations between ROP and the duration and intensity of respiratory support and transfusion exposure. Although altitude itself cannot be evaluated as an independent risk factor in this single-cohort study, these findings underscore the importance of contextualized interpretation of established ROP risk factors in high-altitude neonatal care settings.