{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T17:11:34Z","timestamp":1777482694082,"version":"3.51.4"},"reference-count":59,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:00:00Z","timestamp":1759449600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100023731","name":"Junta de Andaluc\u00eda\u2014Consejer\u00eda de Salud y Consumo","doi-asserted-by":"crossref","award":["PI-0323-2016"],"award-info":[{"award-number":["PI-0323-2016"]}],"id":[{"id":"10.13039\/501100023731","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Late-onset neonatal sepsis (LOS) remains a leading cause of morbidity and mortality in very low birth weight (VLBW) infants (&lt;1500 g and\/or gestational age &lt;32 weeks), with limited preventive strategies. We evaluated whether early enteral bovine lactoferrin (bLf), given its antimicrobial, immunomodulatory, and antioxidant properties, reduces LOS and improves immunologic, antioxidant, and hematologic markers in these infants. Methods: In this randomized, double-blind, placebo-controlled trial, 103 VLBW infants received bLf (150 mg\/kg\/day; n = 50) or the placebo (n = 53) within 72 h of birth for four weeks or until discharge. Outcomes included culture-confirmed LOS, mortality, and major morbidities. Risk ratios (RRs) were calculated, adjusting for gestational age, human milk intake, and ventilatory support when \u226525 events occurred. Pre\/post changes in cytokines, total antioxidant capacity (TAC), and hemoglobin (Hb) were analyzed for interaction effects (time x intervention). Results: bLf reduced LOS (adjusted RR 0.54; 95% CI 0.31\u20130.93; p = 0.028), without differences in other morbidities or mortality. bLf preserved MCP-1 levels, declining in the placebo group (interaction p = 0.022). Among LOS infants receiving bLf, IL-6 remained stable and MCP-1 increased, while both declined in other groups (interaction p = 0.007 for IL-6; p = 0.052 for MCP-1). Although TAC showed a non-significant interaction, the placebo group declined (p = 0.002), while bLf remained stable (p = 0.400) in the post hoc analysis. In non-transfused infants, bLf increased Hb by 0.9 g\/dL vs. controls (p = 0.028). Conclusions: Early bLf supplementation safely reduces LOS in VLBW infants and may support immunologic, antioxidant, and hematologic stability.<\/jats:p>","DOI":"10.3390\/nu17193154","type":"journal-article","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T15:26:54Z","timestamp":1759505214000},"page":"3154","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Preventing Sepsis in Preterm Infants with Bovine Lactoferrin: A Randomized Trial Exploring Immune and Antioxidant Effects"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-5447-5699","authenticated-orcid":false,"given":"Virginia","family":"Plaza-Astasio","sequence":"first","affiliation":[{"name":"University of C\u00f3rdoba, Metabolism and Investigation Unit, Maimonides Institute of Biomedicine Research of C\u00f3rdoba (IMIBIC), Reina Sofia University Hospital, 14004 C\u00f3rdoba, Spain"},{"name":"Neonatology Unit, Reina Sofia University Hospital, 14004 C\u00f3rdoba, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0817-6804","authenticated-orcid":false,"given":"Bel\u00e9n","family":"Pastor-Villaescusa","sequence":"additional","affiliation":[{"name":"University of C\u00f3rdoba, Metabolism and Investigation Unit, Maimonides Institute of Biomedicine Research of C\u00f3rdoba (IMIBIC), Reina Sofia University Hospital, 14004 C\u00f3rdoba, Spain"},{"name":"Primary Care Interventions to Prevent Maternal and Child Chronic Diseases of Perinatal and Developmental Origin (RICORS), RD21\/0012\/0008, Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Network in Maternal, Neonatal, Child and Developmental Health Research (RICORS-SAMID, RD24\/0013\/0007) Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7742-5742","authenticated-orcid":false,"given":"M\u00aa Cruz","family":"Rico-Prados","sequence":"additional","affiliation":[{"name":"Primary Care Interventions to Prevent Maternal and Child Chronic Diseases of Perinatal and Developmental Origin (RICORS), RD21\/0012\/0008, Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Network in Maternal, Neonatal, Child and Developmental Health Research (RICORS-SAMID, RD24\/0013\/0007) Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Department of Biochemistry and Molecular Biology II, School of Pharmacy, Institute of Nutrition and Food Technology \u201cJos\u00e9 Mataix\u201d, Biomedical Research Center, University of Granada, 18016 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4079-6464","authenticated-orcid":false,"given":"Mar\u00eda Dolores","family":"Mesa-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Primary Care Interventions to Prevent Maternal and Child Chronic Diseases of Perinatal and Developmental Origin (RICORS), RD21\/0012\/0008, Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Network in Maternal, Neonatal, Child and Developmental Health Research (RICORS-SAMID, RD24\/0013\/0007) Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Department of Biochemistry and Molecular Biology II, School of Pharmacy, Institute of Nutrition and Food Technology \u201cJos\u00e9 Mataix\u201d, Biomedical Research Center, University of Granada, 18016 Granada, Spain"},{"name":"Instituto de Investigaci\u00f3n Biosanitaria de Granada (ibs.GRANADA), 18016 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Jos\u00e9","family":"P\u00e1rraga-Quiles","sequence":"additional","affiliation":[{"name":"Neonatology Unit, Reina Sofia University Hospital, 14004 C\u00f3rdoba, Spain"},{"name":"Endocrinology and Child Nutrition Unit, Maimonides Institute of Biomedicine Research of C\u00f3rdoba (IMIBIC), Reina Sofia University Hospital, University of C\u00f3rdoba, 14004 C\u00f3rdoba, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Dolores","family":"Ruiz-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Neonatology Unit, Reina Sofia University Hospital, 14004 C\u00f3rdoba, Spain"},{"name":"Endocrinology and Child Nutrition Unit, Maimonides Institute of Biomedicine Research of C\u00f3rdoba (IMIBIC), Reina Sofia University Hospital, University of C\u00f3rdoba, 14004 C\u00f3rdoba, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pilar","family":"Jaraba-Caballero","sequence":"additional","affiliation":[{"name":"Neonatology Unit, Reina Sofia University Hospital, 14004 C\u00f3rdoba, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"In\u00e9s","family":"Tof\u00e9-Valera","sequence":"additional","affiliation":[{"name":"Neonatology Unit, Reina Sofia University Hospital, 14004 C\u00f3rdoba, Spain"},{"name":"Endocrinology and Child Nutrition Unit, Maimonides Institute of Biomedicine Research of C\u00f3rdoba (IMIBIC), Reina Sofia University Hospital, University of C\u00f3rdoba, 14004 C\u00f3rdoba, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2473-0660","authenticated-orcid":false,"given":"Mar\u00eda Jos\u00e9","family":"de la Torre-Aguilar","sequence":"additional","affiliation":[{"name":"University of C\u00f3rdoba, Metabolism and Investigation Unit, Maimonides Institute of Biomedicine Research of C\u00f3rdoba (IMIBIC), Reina Sofia University Hospital, 14004 C\u00f3rdoba, Spain"},{"name":"Primary Care Interventions to Prevent Maternal and Child Chronic Diseases of Perinatal and Developmental Origin (RICORS), RD21\/0012\/0008, Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Network in Maternal, Neonatal, Child and Developmental Health Research (RICORS-SAMID, RD24\/0013\/0007) Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3393-1456","authenticated-orcid":false,"given":"Mar\u00eda Dolores","family":"Ord\u00f3\u00f1ez-D\u00edaz","sequence":"additional","affiliation":[{"name":"University of C\u00f3rdoba, Metabolism and Investigation Unit, Maimonides Institute of Biomedicine Research of C\u00f3rdoba (IMIBIC), Reina Sofia University Hospital, 14004 C\u00f3rdoba, Spain"},{"name":"Neonatology Unit, Reina Sofia University Hospital, 14004 C\u00f3rdoba, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S71","DOI":"10.1055\/s-0040-1714256","article-title":"The Spanish National Network Grupo Castrillo: 22 Years of Nationwide Neonatal Infection Surveillance","volume":"37","year":"2020","journal-title":"Am. J. Perinatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1038\/s41390-021-01721-1","article-title":"Knowledge gaps in late-onset neonatal sepsis in preterm neonates: A roadmap for future research","volume":"91","author":"Kurul","year":"2022","journal-title":"Pediatr. Res."},{"key":"ref_3","unstructured":"Sanchez Tamayo, T. (2024, September 03). Analysis of Morbidity and Mortality Data Results 2019\u20132021 [Internet]. Available online: www.seneo.es."},{"key":"ref_4","unstructured":"Fern\u00e1ndez Colomer, B., and Coto Cotallo, G.D. (2020). Sepsis. Medidas de control. Profilaxis antif\u00fangica. Experto Universitario en Neonatolog\u00eda: Atenci\u00f3n del Reci\u00e9n Nacido Prematuro, Editorial M\u00e9dica Panamericana. [2nd ed.]."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Chong, H.-Y., Tan, L.T.-H., Law, J.W.-F., Hong, K.-W., Ratnasingam, V., Ab Mutalib, N.-S., Lee, L.-H., and Letchumanan, V. (2022). Exploring the Potential of Human Milk and Formula Milk on Infants\u2019 Gut and Health. Nutrients, 14.","DOI":"10.3390\/nu14173554"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Gruden, \u0160., and Poklar Ulrih, N. (2021). Diverse mechanisms of antimicrobial activities of lactoferrins, lactoferricins, and other lactoferrin-derived peptides. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222011264"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1080\/00365549850161557","article-title":"Lactoferricin of Bovine Origin is More Active than Lactoferricins of Human, Murine and Caprine Origin","volume":"30","author":"Vorland","year":"1998","journal-title":"Scand. J. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1007\/s10534-018-0098-2","article-title":"Quality control of commercial bovine lactoferrin","volume":"31","author":"Wakabayashi","year":"2018","journal-title":"Biometals"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1001\/jama.2009.1403","article-title":"Bovine Lactoferrin Supplementation for Prevention of Late-Onset Sepsis in Very Low-Birth-Weight Neonates: A Randomized Trial","volume":"302","author":"Manzoni","year":"2009","journal-title":"JAMA."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/jp.2016.24","article-title":"The Lacuna Trial: A double-blind randomized controlled pilot trial of lactoferrin supplementation in the very preterm infant","volume":"36","author":"Barrington","year":"2016","journal-title":"J. Perinatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1093\/tropej\/fmv044","article-title":"Efficacy of bovine lactoferrin supplementation in preventing late-onset sepsis in low birth weight neonates: A randomized placebo-controlled clinical trial","volume":"61","author":"Kaur","year":"2015","journal-title":"J. Trop. Pediatr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/S0140-6736(18)32221-9","article-title":"Enteral lactoferrin supplementation for very preterm infants: A randomised placebo-controlled trial (ELFIN)","volume":"393","author":"Griffiths","year":"2019","journal-title":"Lancet"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1016\/S2352-4642(20)30093-6","article-title":"The effect of lactoferrin supplementation on death or major morbidity in very low birthweight infants (LIFT): A multicentre, double-blind, randomised controlled trial","volume":"4","author":"Martin","year":"2020","journal-title":"Lancet Child Adolesc. Health"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1097\/INF.0000000000000593","article-title":"Randomized Controlled Trial of Lactoferrin for Prevention of Sepsis in Peruvian Neonates Less than 2500 g","volume":"34","author":"Ochoa","year":"2015","journal-title":"Pediatr. Infect Dis. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.jpeds.2019.12.038","article-title":"Randomized Controlled Trial of Bovine Lactoferrin for Prevention of Sepsis and Neurodevelopment Impairment in Infants Weighing Less Than 2000 Grams","volume":"219","author":"Ochoa","year":"2020","journal-title":"J. Pediatr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.jpeds.2016.04.084","article-title":"Randomized Controlled Trial of Talactoferrin Oral Solution in Preterm Infants","volume":"173","author":"Sherman","year":"2016","journal-title":"J. Pediatr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"S60","DOI":"10.1016\/S0378-3782(14)70020-9","article-title":"Bovine lactoferrin supplementation for prevention of necrotizing enterocolitis in very-low-birth-weight neonates: A randomized clinical trial","volume":"90","author":"Manzoni","year":"2014","journal-title":"Early Hum. Dev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1542\/peds.2011-0279","article-title":"Bovine lactoferrin prevents invasive fungal infections in very low birth weight infants: A randomized controlled trial","volume":"129","author":"Manzoni","year":"2012","journal-title":"Pediatrics"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1055\/s-0034-1371704","article-title":"Oral lactoferrin to prevent nosocomial sepsis and necrotizing enterocolitis of premature neonates and effect on T-regulatory cells","volume":"31","author":"Akin","year":"2014","journal-title":"Am. J. Perinatol."},{"key":"ref_20","first-page":"CD007137","article-title":"Enteral lactoferrin supplementation for prevention of sepsis and necrotizing enterocolitis in preterm infants","volume":"3","author":"Pammi","year":"2020","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Presti, S., Manti, S., Parisi, G.F., Papale, M., Barbagallo, I.A., Volti, G.L., and Leonardi, S. (2021). Lactoferrin: Cytokine modulation and application in clinical practice. J. Clin. Med., 10.","DOI":"10.3390\/jcm10235482"},{"key":"ref_22","first-page":"261","article-title":"Role of lactoferrin supplementation in prevention of late-onset sepsis in preterm neonates","volume":"28","author":"Alshafei","year":"2020","journal-title":"Zagazig Univ. Med. J."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Telang, S. (2018). Lactoferrin: A critical player in neonatal host defense. Nutrients, 10.","DOI":"10.3390\/nu10091228"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1055\/s-0038-1639359","article-title":"Role of Lactoferrin in Neonates and Infants: An Update","volume":"35","author":"Kaufman","year":"2018","journal-title":"Am. J. Perinatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1203\/00006450-200212000-00024","article-title":"Lactoferrin in the Preterm Infants\u2019 Diet Attenuates Iron-Induced Oxidation Products","volume":"52","author":"Raghuveer","year":"2002","journal-title":"Pediatr. Res."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Falsaperla, R., Lombardo, F., Filosco, F., Romano, C., Saporito, M.A.N., Puglisi, F., Piro, E., Ruggieri, M., and Pavone, P. (2020). Oxidative stress in preterm infants: Overview of current evidence and future prospects. Pharmaceuticals, 13.","DOI":"10.3390\/ph13070145"},{"key":"ref_27","first-page":"1","article-title":"Prevention of perinatal group B streptococcal disease\u2014Revised guidelines from CDC, 2010","volume":"59","author":"Verani","year":"2010","journal-title":"MMWR Recomm. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.ajic.2008.03.002","article-title":"CDC\/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting","volume":"36","author":"Horan","year":"2008","journal-title":"Am. J. Infect. Control"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1378\/chest.116.2.462","article-title":"Role of different routes of tracheal colonization in the development of pneumonia in patients receiving mechanical ventilation","volume":"116","author":"Cendrero","year":"1999","journal-title":"Chest"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Rangelova, V., Kevorkyan, A., Raycheva, R., and Krasteva, M. (2024). Ventilator-Associated Pneumonia in the Neonatal Intensive Care Unit\u2014Incidence and Strategies for Prevention. Diagnostics, 14.","DOI":"10.3390\/diagnostics14030240"},{"key":"ref_31","unstructured":"(2025, September 30). Proyecto NeoKissEs. Evaluaci\u00f3n de la Efectividad de un Sistema de Vigilancia sobre las Tasas de Infecci\u00f3n Nosocomial en Reci\u00e9n Nacidos de Muy Bajo Peso. 2nd ed. Barakaldo (Bizkaia, Spain): Hospital Universitario Cruces, Biocruces Health Research Institute; 2015. Available online: http:\/\/www.redsamid.net\/es\/produccion\/proyectos-interes\/proyecto-neokisses.html."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/S0031-3955(16)34975-6","article-title":"Necrotizing Enterocolitis: Treatment Based on Staging Criteria","volume":"33","author":"Walsh","year":"1986","journal-title":"Pediatr. Clin. N. Am."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"International Committee for the Classification of Retinopathy of Prematurity (2005). The International Classification of Retinopathy of Prematurity revisited. Arch. Ophthalmol., 123, 991\u2013999.","DOI":"10.1001\/archopht.123.7.991"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1164\/ajrccm.163.7.2011060","article-title":"Bronchopulmonary dysplasia (NICHD\/NHLBI\/ORD Workshop Summary)","volume":"163","author":"Jobe","year":"2001","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e20153730","DOI":"10.1542\/peds.2015-3730","article-title":"Patent Ductus Arteriosus in Preterm Infants","volume":"137","author":"Benitz","year":"2016","journal-title":"Pediatrics"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"m441","DOI":"10.1136\/bmj.m441","article-title":"Calculating the sample size required for developing a clinical prediction model","volume":"368","author":"Riley","year":"2020","journal-title":"BMJ"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1177\/0962280211427759","article-title":"Extension of the modified Poisson regression model to prospective studies with correlated binary data","volume":"22","author":"Zou","year":"2013","journal-title":"Stat. Methods Med. Res."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Xu, S., Chen, M., Feng, T., Zhan, L., Zhou, L., and Yu, G. (2021). Use ggbreak to Effectively Utilize Plotting Space to Deal With Large Datasets and Outliers. Front. Genet., 12.","DOI":"10.3389\/fgene.2021.774846"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1038\/s41390-021-01749-3","article-title":"Neonatal sepsis definitions from randomised clinical trials","volume":"93","author":"Hayes","year":"2023","journal-title":"Pediatr. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1001\/jamapediatrics.2023.3849","article-title":"Probiotics, Prebiotics, Lactoferrin, and Combination Products for Prevention of Mortality and Morbidity in Preterm Infants: A Systematic Review and Network Meta-Analysis","volume":"177","author":"Wang","year":"2023","journal-title":"JAMA Pediatr."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1055\/s-0039-1696676","article-title":"Lactoferrin Supplementation to Prevent Late-Onset Sepsis in Preterm Infants: A Meta-Analysis","volume":"38","year":"2021","journal-title":"Am. J. Perinatol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Piersigilli, F., Van Grambezen, B., Hocq, C., and Danhaive, O. (2020). Nutrients and microbiota in lung diseases of prematurity: The placenta-gut-lung triangle. Nutrients, 12.","DOI":"10.3390\/nu12020469"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Gao, Y., Hou, L., Lu, C., Wang, Q., Pan, B., Wang, Q., Tian, J., and Ge, L. (2020). Enteral Lactoferrin Supplementation for Preventing Sepsis and Necrotizing Enterocolitis in Preterm Infants: A Meta Analysis With Trial Sequential Analysis of Randomized Controlled Trials. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.01186"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Teng, M., Wu, T.-J., Jing, X., Day, B.W., Pritchard, K.A., Naylor, S., and Teng, R.-J. (2024). Temporal Dynamics of Oxidative Stress and Inflammation in Bronchopulmonary Dysplasia. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms251810145"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"361","DOI":"10.4137\/BMI.S834","article-title":"Pulmonary Biomarkers of Bronchopulmonary Dysplasia","volume":"3","author":"Thompson","year":"2008","journal-title":"Biomark Insights."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/aps.2013.200","article-title":"Immunomodulatory effects of lactoferrin","volume":"35","year":"2014","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_47","unstructured":"Gordon, S.M., Srinivasan, L., Catherine Harris, M., and Kilpatrick, L.E. (2022). CHAPTER 121-Cytokines and Inflammatory Response in the Fetus and Neonate. Fetal and Neonatal Physiology, Elsevier."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Melville, J.M., and Moss, T.J.M. (2013). The immune consequences of preterm birth. Front. Neurosci., 7.","DOI":"10.3389\/fnins.2013.00079"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1038\/s41467-019-08794-x","article-title":"Dynamic molecular changes during the first week of human life follow a robust developmental trajectory","volume":"10","author":"Lee","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"6868","DOI":"10.4049\/jimmunol.180.10.6868","article-title":"Lactoferrin acts as an alarmin to promote the recruitment and activation of antigen-presenting cells and antigen-specific immune responses","volume":"180","author":"Yang","year":"2008","journal-title":"J. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Kruzel, M.L., Zimecki, M., and Actor, J.K. (2017). Lactoferrin in a context of inflammation-induced pathology. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.01438"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2549","DOI":"10.1007\/s00018-005-5370-2","article-title":"Lactoferrin: A modulator of immune and inflammatory responses","volume":"62","author":"Legrand","year":"2005","journal-title":"Cell Mol. Life Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"S53","DOI":"10.1016\/j.tube.2016.09.011","article-title":"Recombinant human lactoferrin modulates human PBMC derived macrophage responses to BCG and LPS","volume":"101","author":"Hwang","year":"2016","journal-title":"Tuberculosis"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1023\/B:BIOM.0000027696.48707.42","article-title":"Lactoferrin and host defence: An overview of its immuno-modulating and anti-inflammatory properties","volume":"17","author":"Legrand","year":"2004","journal-title":"BioMetals"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Lembo, C., Buonocore, G., and Perrone, S. (2021). Oxidative stress in preterm newborns. Antioxidants, 10.","DOI":"10.3390\/antiox10111672"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Lorenzetti, S., Pl\u00f6sch, T., and Teller, I.C. (2021). Antioxidative molecules in human milk and environmental contaminants. Antioxidants, 10.","DOI":"10.3390\/antiox10040550"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Yang, X., Jiang, S., Deng, X., Luo, Z., Chen, A., and Yu, R. (2022). Effects of Antioxidants in Human Milk on Bronchopulmonary Dysplasia Prevention and Treatment: A Review. Front. Nutr., 9.","DOI":"10.3389\/fnut.2022.924036"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Boles\u0142awska, I., Boles\u0142awska-Kr\u00f3l, N., Jakubowski, K., Przys\u0142awski, J., and Drzyma\u0142a-Czy\u017c, S. (2025). Lactoferrin\u2014A Regulator of Iron Homeostasis and Its Implications in Cancer. Molecules, 30.","DOI":"10.3390\/molecules30071507"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"543","DOI":"10.24953\/turkjped.2022.670","article-title":"Lactoferrin as treatment for iron-deficiency anemia in children: A systematic review","volume":"65","author":"June","year":"2023","journal-title":"Turk. J. Pediatr."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/19\/3154\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T07:56:53Z","timestamp":1760428613000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/19\/3154"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,3]]},"references-count":59,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["nu17193154"],"URL":"https:\/\/doi.org\/10.3390\/nu17193154","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,3]]}}}