Lutein and Zeaxanthin Supplementation in Preterm Very Low-Birth-Weight Neonates in Neonatal Intensive Care Units: A Multicenter Randomized Controlled Trial

Abstract

Background Human milk feeding protects against oxidative stress-induced damage in preterm neonates, including severe multifactorial diseases such as retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), and bronchopulmonary dysplasia (BPD). The carotenoids, which are not found in formula milk, might play a key role in these actions. Methods A multicenter, double-blind, randomized controlled trial was conducted in three tertiary Italian neonatal intensive care units. All preterm infants <32 +6 weeks' gestational age were eligible and were randomized to a single, oral, daily 0.5-mL dose of carotenoid supplementation (0.14 mg lutein + 0.0006 mg zeaxanthin) or placebo (5% glucose solution) from birth till 36 weeks' corrected gestational age. Primary outcomes were threshold ROP, NEC > second stage, and BPD. Surveillance for detection of these diseases and for intolerance/adverse effects was performed.Results No treatment-related adverse effect was documented in the 229 analyzed infants, whose clinical/demographical characteristics were similar in the two groups. Threshold ROP incidence did not significantly differ in treated (6.2%) versus not treated infants (10.3%; p ¼ 0.18). The same occurred for NEC (1.7% versus 5.1%; p ¼ 0.15) and BPD (4.5% versus 10.3%; p ¼ 0.07). Noteworthy, the progression rate from early ROP stages to threshold ROP was decreased by 50% (0.30 versus 0.44; p ¼ 0.23). Conclusion Lutein/zeaxanthin supplementation in preterm infants is well tolerated. No significant effect was seen on threshold ROP, NEC, or BPD. The decreasing trends of these outcomes in the treatment group need to be assessed and confirmed on larger sample-sizes.

Status of Vitamin A and Related Compounds and Clinical Outcomes in Maternal-Infant Pairs in the Midwestern United States

“…In another study by Manzoni et al [34], the effect of lutein + zeaxanthin on prevention of BPD appears relevant, although not statistically significant ( p = 0.07). Lutein supplementation also has been shown to result in greater rod photoreceptor sensitivity responses when compared to controls [32].…”

Leveraging Bioactives to Support Human Health through the Lifecycle: Scientific Evidence and Regulatory Considerations

“…There are preliminary data to suggest a potential protective role of carotenoids against oxidative stress during premature life, particularly in cases of retinopathy of prematurity (ROP) [59].…”

“…Moreover, the important beneits of probiotics is based on their ability to metabolize complex carbohydrates and produce lactic acid and SCFAs such as butyrate [58,59]. In the context of IBS, there is ample evidence to support the role of probiotics in managing the symptoms of IBS through positive changes in the composition and functionality of the intestinal bacteria, correcting intestinal motility, limiting visceral hypersensitivity, modulating immune responses and beneiting the gut-brain axis [71].…”

Role of macular xanthophylls in prevention of common neovascular retinopathies: Retinopathy of prematurity and diabetic retinopathy

“…To date, four RCTs have investigated the relationship between xanthophylls and ROP [17,[143][144][145]. All studies included preterm infants <33 weeks gestational age.…”