Critical period of oxygen supplementation and invasive ventilation: implications for severe retinopathy of prematurity

Several studies have identified graded oxygen saturation targets to prevent retinopathy of prematurity (ROP), a serious complication in preterm infants. We aimed to analyze the critical period of oxygen supplementation and/or invasive ventilation associated with severe ROP. This retrospective case-control study included neonates with a gestational age (GA) < 29 weeks. Participants were divided into two groups: treated retinopathy and untreated/no retinopathy. Time-weighted average FiO2 (TWAFiO2) and weekly invasive ventilation were compared between groups by postnatal age (PNA) and postmenstrual age (PMA). The association of treated retinopathy with TWAFiO2 and invasive ventilation was analyzed. Data from 287 neonates were analyzed; 98 were treated for ROP and had lower GAs (25.5 vs. 27.4 weeks, p < 0.01) and lower birthweights (747.6 vs. 1014 g, p < 0.001) than those with untreated/no ROP. TWAFiO2 was higher from PMA 26–34 weeks, except for PMA 31 weeks in treated ROP, and higher in the first nine weeks of life in treated ROP. On multiple logistic regression, TWAFiO2 and invasive ventilation were associated with ROP treatment during the first seven weeks PNA. Invasive ventilation was associated with ROP treatment from PMA 26–31 weeks; no association was found for TWAFiO2 and PMA. Amount of oxygen supplementation and/or invasive ventilation during the first 7 weeks of life or up to 31 weeks PMA was associated with development of severe ROP. This period might be candidate timing for strict oxygen supplementation strategies in preterm infants, while concerns of mortality with low oxygen supplementation should be further explored.