Lutein supplementation in very low birth weight (VLBW) neonates in neonatal intensive care units (NICU)

INTERVENTION: 1. The regimens in the two intervention groups will be : Group A: 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) Group B: placebo (0.5 ml of a 5% glucose solution) . 2. Drug and placebo will be administered in a single oral daily dose from birth till the 36th week of gestational age (corrected age). 3. Administration will start within the first 48 h of life 4. Neonates not feeding in the first 48 hours will receive the drug/placebo by oral/naso‐gastric tube and can be enrolled in the absence of gastric instability and/or repeated gastric residuals or vomit. 5. If they repeatedly display gastric instability, gastric residuals or vomit, they may be enrolled at any point during the first week of life, depending on the first "efficacious" feedings. The day of life in which they first received the drugs/placebo is started will be recorded in the database, and their statistics will be limited to the days of administration exposure to intervention. CONDITION: Disorders of preterm very low birth weight infants ; Pregnancy and Childbirth PRIMARY OUTCOME: The primary objective of the study will be to evaluate the effectiveness of Lutein with Zeaxanthin compared to placebo in the prevention of ROP of any stage, BPD, and NEC of surgical stage (i.e., 2nd or greater according to Bell classification) in the preterm neonates <32+6 wks g.a. admitted to the participant NICUs. Surveillance for detection of these diseases, as well as for intolerance/adverse effects will be performed till discharge. Measurements of serum liver enzymes values will be also performed at 4 wks of age. SECONDARY OUTCOME: 1. Assessment of the incidence of NEC of all stages; 2. Intestinal perforation; 3. Late‐onset sepsis; 4. Mortality prior to discharge; 5. Death or NEC (all stages); 6. Death or sepsis or NEC (surgical stage); 7. Severe (grade 3‐4) intraventricular haemorrhage; 8. Liver failure INCLUSION CRITERIA: All neonates with gestational age (g.a.) less than 32 wks + 6 days (i.e., all those qualifying for screening of ROP) born within the study period, whether at one of the participant Institutions or elsewhere, were eligible for the study.