A prospective, randomized, double blind study comparing lutein to placebo for reducing occurrence and severity of retinopathy of prematurity

Abstract

Lutein has been shown to have antioxidant functions in newborns and with zeaxantin selectively taken up into the macula of the eye. We hypothesize that lutein administration may contribute to reducing the incidence of Retinopathy of Prematurity (ROP). This was a single center, double-blind randomized controlled study. Preterm infants with gestational age (GA) ≤ 32 weeks able to tolerate minimal enteral feeding before the seventh day of life (DOL) were enrolled; lutein and zeaxantin plasma concentrations and ROP occurrence and severity were evaluated. Sixty-three newborns were enrolled, 31 in the lutein group and 32 in the placebo group (one died before ROP assessment). The mean GA was 29.9 (± 1.9) weeks and the mean birth weight was 1331 (± 415) grams. There were no differences in the incidence of ROP at any stage between groups. Oxidative injury is probably an additional mechanism of damage of the developing retinal vessels, and it probably plays only a minor role in the pathogenesis of ROP. Supplementation with antioxidant substances might have beneficial effects noticeable only on larger samples of high risk neonates or at very high dosage. Further investigations would be needed to evaluate whether lutein supplementation can influence functional rather than anatomical outcomes in preterm infants.

Response to ‘May be the formula supplementation with lutein actually be effective on visual development in preterm infants?’

“…As expected, that trial found no differences between groups on plasma cholesterol or triglyceride levels. 3 It is highly unlikely that there would be an unexplained systematic difference in plasma lipids in our larger study populations.…”

“…Second, Romagnoli et al 3 previously proposed further investigations would be needed to evaluate whether lutein supplementation can influence functional rather than structural vision outcomes in preterm infants. 3 Our trial demonstrated that dietary lutein improved rod photoreceptor function in these infants.…”

“…But it is intriguing that Rubin et al 2 (seven sites), Dani et al 4 (five sites) and Manzoni et al 5 (three sites) each showed a trend of decreased ROP severity (stages three to five or Plus disease) among the luteinsupplemented groups. Romagnoli et al 3 (one site) had few subjects. Consequently, it remains undetermined whether lutein supplementation can decrease the incidence or severity of ROP in at-risk preterm infants.…”

“…Of the four randomized clinical trials in which lutein and zeaxanthin were given to preterm infants, [2][3][4] we provided carotenoids as a part of the ingredient matrix of infant formula. The daily dietary lutein was derived from the lutein levels found in human milk and colostrum.…”

May be the formula supplementation with lutein actually effective on visual development in preterm infants?

“…2 We recently found that oral supplementation of preterm infant with gestational age p32 weeks with 0.5 mg Kg -1 per day of lutein do not influence the occurrence and severity of retinopathy of prematurity (ROP). 3 In the Rubin study, the carotenoids-supplemented formula contains 211 mg per l of lutein, so, assuming that a full enteral feed-preterm infant takes about 150-160 ml Kg -1 per day of formula, we can deduce that the infants supplemented in the study finally received about 0.03 mg Kg -1 per day of lutein. We wonder how the authors explain that this low dose of lutein may affect the severity of ROP and the retinal neurovascular development, as they report that fewer infants developed severe ROP in the supplemented formula (8%) than in the control formula (28%) group, and that the supplemented group had greater rod photoreceptor sensitivity.…”