Tocopherol efficacy and safety for preventing retinopathy of prematurity: a randomized, controlled, double-masked trial.
To test the efficacy and safety of vitamin E in preventing retinopathy of prematurity, 287 infants with birth weights of less than 1.5 kg or gestational ages of less than 33 weeks were enrolled within 24 hours of birth in a randomized, double-masked trial of IV, followed by oral, placebo v tocopherol (adjusted to plasma levels of 3 to 3.5 mg/dL). In the 196 infants completing ophthalmic follow-up, tocopherol did not prevent retinopathy of prematurity of any stage (28% placebo treated v 26% tocopherol treated) or moderately severe retinopathy of prematurity (8% placebo treated v 11% tocopherol treated). Cicatricial sequelae were not significantly different (1/97 placebo treated v 3/99 tocopherol treated), with one placebo-treated infant and one tocopherol-treated infant having retinal detachments. Among all 232 infants examined, those treated with tocopherol had more retinal hemorrhage than placebo-treated infants (8/121 placebo treated v 16/111 tocopherol treated), and retinal hemorrhage correlated positively (P less than .01) with plasma levels of tocopherol after the first 2 weeks of age. Prospective monitoring of morbidity including late-onset sepsis, necrotizing enterocolitis, etc revealed no differences between groups except that grades 3 and 4 intraventricular hemorrhage occurred more frequently in infants weighing less than 1 kg at birth who had received tocopherol (14/42, 33%) v those who had received placebo (4/43, 9%) (P less than .02). Our data do not support the use of tocopherol for prophylaxis against retinopathy of prematurity in premature infants and suggest that IV tocopherol treatment starting on day 1 may increase the incidence of hemorrhagic complications of prematurity, particularly in infants with birth weights of less than 1 kg.
D001724:Birth Weight; D002543:Cerebral Hemorrhage / Q000139:chemically induced; D002986:Clinical Trials as Topic; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007231:Infant, Newborn; D007235:Infant, Premature, Diseases / Q000139:chemically induced / Q000150:complications / Q000401:mortality; D008297:Male; D011897:Random Allocation; D012163:Retinal Detachment / Q000209:etiology; D012166:Retinal Hemorrhage / Q000139:chemically induced; D012178:Retinopathy of Prematurity / Q000097:blood / Q000150:complications / Q000517:prevention & control*; D014810:Vitamin E / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*
D014810:Vitamin E