Lactoferrin Supplementation to Prevent Late-Onset Sepsis in Preterm Infants: A Meta-Analysis

Abstract

Objective To systematically review and meta-analyze the role of lactoferrin supplementation to prevent late-onset sepsis (LOS) in preterm infants. Study Design Database search include PubMed, Web of Science, and Cochrane central for randomized clinical trial (RCTs). The Cochrane Grading of Recommendations Assessment, Development, and Evaluation methodology was used for summarizing the results. Results Ten RCTs involving 3,679 infants were included. Lactoferrin supplementation with or without probiotics decreased all LOS (relative risk [RR]: 0.56; 95% confidence interval [CI]: 0.36–0.86; I 2 = 58%; 10 studies; 3,470 subjects; level of evidence [LOE]: low) significantly. Similarly, lactoferrin supplementation without probiotics decreased all LOS (RR: 0.43; 95% CI: 0.29–0.62; I 2 = 0%; 8 studies; 1,209 subjects; LOE: moderate) significantly. Lactoferrin supplementation did not significantly reduce necrotizing enterocolitis (RR: 0.62; 95% CI: 0.29–1.33; I 2 = 43%; 6 studies; 3,079 subjects; LOE: low), all-cause mortality (RR: 0.74; 95% CI: 0.36–1.53; I 2 = 53%; 8 studies; 3,395 subjects; LOE: very low), bronchopulmonary dysplasia (RR: 1; 95% CI: 0.90–1.13; I 2 = 0%; 4 studies; 2,570 subjects; LOE: moderate), and threshold retinopathy of prematurity eligible for surgical treatment (RR: 0.61; 95% CI: 0.25–1.51; I 2 = 74%; 2 studies; 2,481 subjects; LOE: very low). Conclusion Low to moderate quality evidence suggests that lactoferrin supplementation reduces LOS in preterm infants. Further research is needed to improve the certainty in the evidence.

Lactoferrin as potential preventative and adjunct treatment for COVID-19

“…Given promising laboratory and animal studies, Lf has been investigated in a number of clinical settings against sepsis. Recently, a meta-analysis of 10 randomised controlled trials involving 3679 infants concluded that Lf reduces late-onset sepsis in pre-term infants [31] ⁠. Separately, a human recombinant Lf, talactoferrin, was studied in a phase 2 clinical trial to assess the outcome in severe sepsis and a 12.5% reduction in all-cause mortality was found in those treated with talactoferrin [32] , but the results were regrettably not replicated in a follow-up phase 2/3 trial [33] .…”

Nutraceutical Approach to Preventing Coronavirus Disease 2019 and Related Complications

“…Due to the promising results got in experimental studies, lactoferrin has been investigated in some clinical studies against sepsis and recently, a meta-analysis of well-performed randomised controlled trials involving about 4000 infant showed that lactoferrin reduces late-onset sepsis ( 101 )⁠.…”

Caregivers Perspective Towards Use of Enteral Lactoferrin Supplementation In Newborn Infants; Formative Research Findings

“…Human lactoferrin (hLF) and bovine lactoferrin (bLF) have similar bioactivity as proven in vitro and animal models (7). The US Food and Drug Administration has recognized bLF a safe nutrient to add in infant formula with no adverse effects (8). A pilot study in the United States (US) reported a protective effect of bLF enhanced formula (containing bLF 850 mg/L) on lower respiratory tract illnesses compared to regular formula in infants (6).…”

“…A pilot study in the United States (US) reported a protective effect of bLF enhanced formula (containing bLF 850 mg/L) on lower respiratory tract illnesses compared to regular formula in infants (6). Another study described it as a safe product that has the potential to reduce sepsis in low birth-weight (LBW) infants (8,9). Furthermore, it is considered the most effective intervention contributing towards the reduction in neonatal mortality (10).…”