Vitamin E supplementation in preterm infants reduced the risk of intracranial hemorrhage but increased the risk of sepsis. In very low birth weight infants it increased the risk of sepsis, and reduced the risk of severe retinopathy and blindness among those examined. Evidence does not support the routine use of vitamin E supplementation by intravenous route at high doses, or aiming at serum tocopherol levels greater than 3.5 mg/dl.

For more than 50 years it has been known that oxygen therapy can lead to retinopathy of prematurity (ROP). Recent clinical research has led many neonatologists to lower the target oxygen saturation alarm limits to 85–93% and to titrate the inspired oxygen in small increments. Despite efforts to optimize oxygen therapy, the number of cases of severe ROP remains high as more extremely low birth weight infants survive. Based on new insights into the pathogenesis of ROP, there are multiple interventions, in addition to optimizing oxygen therapy that may help decrease severe ROP. Interventions that have the potential to prevent phase I ROP (birth to ≤32 weeks PMA) include increasing retinal erythropoietin (exogenous rHuEPO) and serum IGF-1 (breast milk and/or exogenous IGF-1), maintaining serum glucose below 120 mg, and providing omega-3 supplements. Interventions with potential to prevent proliferative ROP in phase II (infants >32–34 weeks PMA) include treating anemia with a liberal policy of transfusion in premature infants with stage III ROP, photopic adaptation, vitamin E supplements (>34 weeks PMA), and omega-3 supplements. The WINROP algorithm has shown promise as a biomarker in the early identification of extremely low birth weight infants at high risk for proliferative ROP. As there is interplay of multiple factors in the causation of ROP, we suggest that the simultaneous application of some combination of multiple interventions, mentioned above, may reduce the burden of ROP in the most vulnerable infants. These conceptsneed study in well-designed randomized clinical trials before being incorporated into clinical practice.

The incidence of retinopathy of prematurity (ROP) is showing an increasing trend in the United States. This may be because of increasing survival rates among extremely preterm infants (<25 weeks’ gestation) and targeting higher oxygen saturation. Five randomized clinical trials of low versus high oxygen saturation target ranges found increased mortality in the low oxygen saturation target group and an increased incidence of ROP in the high oxygen saturation target group. The American Academy of Pediatrics recommends using an oxygen saturation target range of 90% to 95% in extremely low-birthweight infants. The change of practice to target this higher oxygen saturation range, from admission until discharge, may be contributing to the increasing incidence of ROP in extremely preterm infants. To decrease the incidence of ROP without increasing mortality, 2 new cohort trials suggest gradually increasing oxygen saturation targets as preterm infants mature. There is evidence that human milk, vitamin A, and omega-3 fatty acids can help, in addition to continuous oxygen saturation monitoring, to decrease the risk of ROP. We review this literature and provide a meta-analysis to evaluate the evidence.

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