Lutein and zeaxanthin supplementation in preterm infants in NICU: Preliminary data from a multicentre RCT

Abstract

Preterm infants are at high risk of oxidative stress-induced damage and diseases, including severe multifactorial outcomes of prematurity such as ROP, NEC and BPD. Human milk feedings of preterms is speculated having a protective role towards these diseases, namely against ROP and NEC. The carotenoids (lutein, b-carotene, and zeaxanthin) are a family of polyene, lipophilic molecules found in human milk but not in formulas. These molecules might account for the protective role of human milk, providing protection against both light-induced and metabolic oxidative damages in the retina and in other developing tissues. The aim of this study was to evaluate the relationships of supplemented carotenoids (lutein and zeaxanthin) with the outcomes of preterm infants, namely ROP, NEC and BPD. We report the preliminary data of a multicentre RCT conducted in three tertiary NICUs of Italy. All VLBW infants < 33 wks g.a. were eligible. They were randomized to lutein/zeaxanthin supplementation (14 drops, i.e. 0.5 ml, meaning 0.14 mg of lutein and 0.0006 mg of zeaxanthin; LuteinOfta gtt, NEOOX Division of SOOFT Italia s.p.a., Montegiorgio, Italy; group A) or placebo (same amount of glucose solution; group B) from birth till the 36th wk g.a. corrected age. Drugs and placebo were administered in a single oral daily dose. The primary outcomes were ROP (threshold and all-stage), NEC (> 2nd stage) and BPD (defined as the need for oxygen supplementation at 36 wks of age). Surveillance for detection of these diseases, as well as for intolerance/adverse effects was performed till discharge. Measurements of serum liver enzyme values were performed at 4 wks of age. This preliminary analysis included 107 infants. Their clinical and demographical characteristics did not differ between the two groups. Overall, threshold ROP incidence tended to be lower in 54 treated (9.4%) vs. 53 not-treated (13.0%) infants ( p = 0.39). The same occurred for BPD (3.8% vs. 13.0%; p = 0.08) and NEC (2.1 vs. 4.8%; p = 0.45). Of note, treatment was associated with less need of mechanical ventilation (8 vs. 14 days), lower peak levels of bilirubinemia (9 mg% vs. 10 mg%), and less days of stay in NICU (38 vs. 42 days). No adverse effects putatively attributable to the treatment were documented. Based on these preliminary data from an RCT, lutein/zeaxanthin supplementation in VLBW infants was well tolerated and associated with a trend towards lower incidences of threshold ROP, NEC and BPD. These trends need to be confirmed and to achieve significance on larger sample sizes. We speculate that carotenoids are important nutrients in decreasing the severity of oxidative stress-related diseases of prematurity.