Shahed University Immunoregulation 2588_5200 8 1 2026 08 26 Effectiveness of Lutein Supplementation in Reducing Morbidity and Mortality in Preterm Infants 5236 10.32598/Immunoregulation.8.29 EN Reza Saeidi Neonatal Health Research Center, Research Institute for Children’s Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 0000-0002-9033-3321 Mohammad Kordkatouli Department of Genetics, Faculty of Advanced Sciences and Technology, TeMS.C, Islamic Azad University, Tehran, Iran. 0009-0006-3008-6820 Journal Article 2026 05 23 <strong>Background</strong>: Preterm infants are born with deficient antioxidant systems and miss the crucial third trimester transfer of lutein and zeaxanthin. These carotenoids protect the retina and brain from oxidative stress. This deficiency contributes to major neonatal morbidities, including retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), and intraventricular hemorrhage (IVH). This narrative review aimed to evaluate the efficacy and safety of postnatal combined lutein and zeaxanthin supplementation in preterm infants, focusing on its impact on neonatal morbidity and mortality.<br><strong>Materials and Methods:</strong> A structured narrative synthesis of peer-reviewed literature from 2000 to 2025 was conducted. The primary evidence source was the 2025 Cochrane Systematic Review, which included five randomized controlled trials (RCTs) with 666 preterm infants.<br><strong>Results</strong>: Supplementation appeared safe and well-tolerated short-term; however, long-term safety remains unestablished, and the sample size was insufficient to detect rare adverse events. The Cochrane meta-analysis reported a probable reduction in severe ROP (risk ratio [RR] 0.49, 95% confidence interval [CI], 0.29%, 0.81%; moderate-certainty evidence). No significant effects were observed for any-stage ROP, mortality, IVH, necrotizing enterocolitis (NEC), BPD, or sepsis. All evidence derives from combined lutein and zeaxanthin, preventing isolation of individual carotenoid effects.<br><strong>Conclusion</strong>: Combined lutein and zeaxanthin supplementation appears safe in the short term and likely reduces severe ROP. However, long-term safety remains unestablished, and cautious interpretation is warranted. Current evidence shows no benefit for other major morbidities or mortality. Large-scale RCTs with extended follow-up and systematic safety monitoring are urgently needed before routine clinical adoption. https://immunoreg.shahed.ac.ir/article_5236_78289d91e9c4adcf4e97d6b3d4df6ae0.pdf