Infection, oxygen, and immaturity: interacting risk factors for retinopathy of prematurity.

BACKGROUND Interactions among known risk factors for retinopathy of prematurity (ROP) remain to be clarified. OBJECTIVES The aim of this study was to identify risk factors associated with ROP and to explore the interrelationships between prominent risk factors for ROP. METHODS From an institutional cohort of 1,646 very preterm newborns with gestational age <30 weeks or birth weight <1,501 g, we selected infants with a gestational age <30 weeks who met the criteria for ROP screening (n = 622) for a nested case-control analysis. RESULTS Of the 622 eligible newborns, 293 (47%) were diagnosed with ROP. From multivariable analyses, gestational age <26 weeks (OR 2.9, CI 1.7-4.9), oxygen exposure at 28 days (OR 1.7, CI 1.0-2.7), and neonatal sepsis (OR 2.1, CI 1.4-3.2) emerged as prominent risk factors for ROP. Oxygen- associated ROP risk was more prominent among infants of 23-25 weeks' gestational age, while infection-associated ROP risk was higher among infants born at 28-29 weeks. The OR for the joint effect of all 3 risk factors (23.5) was higher than would have been expected under the additive (8.6) and the multiplicative (16.5) patterns of interaction. CONCLUSIONS Our study suggests that neonatal sepsis, oxygen exposure, and low gestational age are not only independently associated with a significantly increased risk of ROP, but also interact beyond additive and even multiplicative patterns.