Lactoferin - A Neuroprotective Molecule in Children: Overview of Current Evidence and Future Prospects (Systematic Review and Metaanalysis)

Background: This systematic review and meta-analysis aims to summarize the most recent literature data on the neuroprotective role of lactoferin and also to highlight its supporting effects during brain developmental injury or after perinatal brain injury in the pediatric population. Methods: We conducted a systematic review following PRISMA guidelines. A comprehensive search across PubMed, Scopus, Web of Science, and Cochrane Library identified studies assessing lactoferin’s impact on pediatric neurodevelopment, with quality appraisal performed using Cochrane, Newcastle-Ottawa, and GRADE criteria. Results: Out of 1,172 identified records, 13 studies (5 human, 8 animal) met the inclusion criteria. Human studies reported that lactoferin supplementation improved brain development, cognitive function, neurodevelopmental scores, and sleep quality in children. Animal models supported these findings, showing enhanced neuroprotection and reduced oxidative damage. A meta-analysis of two RCTs revealed a moderate positive effect of lactoferin on cognitive function (SMD = 0.53), with low heterogeneity (I² = 0%). Overall, evidence quality ranged from moderate to low, as assessed by GRADE. Conclusions: Lactoferin, by its multiple properties and mechanisms of action, seems to have a neuroprotective role in children, demonstrated both in clinical and preclinical studies. Further investigations are needded for the establishment of an effective dose range in the pediatric population.