The Role of Lactoferrin in Modulating Inflammation and Preventing Preterm Birth: A Narrative Review

Background: Preterm birth (PTB) is a major cause of neonatal morbidity and mortality worldwide. Inflammatory cytokines, especially IL-6, play a pivotal role in PTB pathogene-sis. Lactoferrin (LF), an iron-binding glycoprotein, possesses antimicrobial and immuno-modulatory properties that may reduce PTB risk. This narrative review aims to synthesize evidence on LF supplementation effects on inflammation, cytokine modulation, biochem-ical markers, and obstetric outcomes linked to PTB. Methods: Eight clinical studies from Italy involving 728 pregnant women at risk of PTB were analyzed. LF was administered orally, vaginally, or both, with varying dosages and durations. Outcomes included in-flammatory markers (IL-6, prostaglandins), cervical and uterine parameters, oxidative stress biomarkers, and clinical endpoints such as PTB rates and neonatal intensive care unit (NICU) admissions. Results: LF supplementation consistently reduced cervi-co-vaginal and serum IL-6 levels (e.g., p ≤ 0.005), decreased prostaglandin concentrations (p < 0.01), and improved cervical length (p < 0.0001) while lowering uterine contraction frequency (p = 0.05). Oxidative stress markers significantly improved (p < 0.0001). Clini-cally, LF-treated groups exhibited reduced PTB incidence (25.0% vs 44.6%; p = 0.02), high-er gestational age at delivery (37.7 ± 3.2 vs 35.9 ± 4.1 weeks; p = 0.01), and fewer NICU ad-missions (8.3% vs 21.5%; p = 0.05). Immunological profiles indicated decreased pro-inflammatory cytokines and increased immune-regulatory factors in amniotic fluid. Conclusions: LF demonstrates a multifaceted immunomodulatory effect that mitigates in-flammation and improves obstetric and neonatal outcomes associated with PTB risk. These findings support LF’s potential as a preventive intervention against PTB, high-lighting the need for further large-scale randomized trials.