Related Experiment Video
Updated: May 28, 2026
Effect of Hyaluronic Acid 35 kDa on an In Vitro Model of Preterm Small Intestinal Injury and Healing Using Enteroid-Derived Monolayers
Published on: July 28, 2022
Oral lactoferrin for the prevention of sepsis and necrotizing enterocolitis in preterm infants
1Section of Neonatology, Department of Pediatrics, Baylor College of Medicine, 6621, Fannin, MC.WT 6-104, Houston, Texas, USA, 77030.
Insights
Oral lactoferrin supplementation significantly reduces late-onset sepsis in preterm neonates, especially those under 1000g. However, it does not prevent necrotizing enterocolitis (NEC) when given alone.
Area of Science:
- Neonatal Medicine
- Infectious Disease Prevention
- Nutritional Science
Background:
- Lactoferrin, a natural protein in human milk, plays a role in host defense.
- It is being investigated for its potential to prevent sepsis and necrotizing enterocolitis (NEC) in preterm infants.
Purpose of the Study:
- To evaluate the safety and effectiveness of oral lactoferrin for preventing sepsis and NEC in preterm neonates.
- To analyze its impact on different infant subgroups and feeding practices.
Main Methods:
- Systematic review of randomized and quasi-randomized controlled trials.
- Searches included Cochrane Neonatal Review Group, MEDLINE, EMBASE, CINAHL, and trial registries up to July 2011.
Main Results:
- One trial involving 472 very low birth weight infants was analyzed.
- Oral lactoferrin, alone or with Lactobacillus rhamnosus GG, significantly reduced late-onset sepsis.
- Lactoferrin alone did not prevent NEC, but the combination with Lactobacillus rhamnosus GG did. No adverse effects were reported.
Conclusions:
- Oral lactoferrin prophylaxis effectively reduces late-onset sepsis in preterm infants (<1500g), particularly those <1000g.
- Lactoferrin alone shows no efficacy in preventing NEC; combination therapy is more promising.
- Further research is needed on optimal dosing, duration, and type of lactoferrin, and the role of maternal milk feeding.
Background:
Lactoferrin, a normal component of human colostrum, milk, tears and saliva can enhance host defence and may be effective in the prevention of sepsis and necrotizing enterocolitis (NEC) in preterm neonates.
Objectives:
To assess the safety and effectiveness of oral lactoferrin in the prevention of sepsis and NEC in preterm neonates.
Search Strategy:
We used the search strategy of the Cochrane Neonatal Review Group (CNRG) including searches of CENTRAL (The Cochrane Library), MEDLINE and PREMEDLINE, EMBASE and CINAHL. We also searched trials registries and the conference proceedings of Pediatric Academic Society. Searches updated in July 2011.
Selection Criteria:
Randomized or quasi-randomized controlled trials evaluating oral lactoferrin at any dose or duration for the prophylaxis of sepsis or NEC in preterm neonates.
Data Collection And Analysis:
Data collection and analysis were performed according to the standard methods of the CNRG.
Main Results:
One trial (Manzoni 2008) that randomized 472 very low birth weight infants was eligible. A statistically significant reduction in late-onset sepsis was observed in the groups that received either lactoferrin alone (RR 0.34, 95% CI 0.17 to 0.70) or in combination with Lactobacillus rhamnosus GG (RR 0.27, 95% CI 0.12 to 0.60).In subgroup analyses, infants weighing less than 1000 g and those fed exclusively on maternal milk had a significant reduction in late-onset sepsis after oral lactoferrin supplementation alone. In the group supplemented with oral lactoferrin and Lactobacillus rhamnosus, infants weighing less than 1000 g had a significant reduction in late-onset sepsis, a result not seen in infants fed maternal milk exclusively.Prophylaxis with oral lactoferrin alone did not reduce the incidence of NEC (RR 0.33, 95% CI 0.09 to 1.17), but a significant reduction in NEC with a combination of lactoferrin and Lactobacillus rhamnosus GG was noted (RR 0.05, 95% CI 0.00 to 0.90).No adverse effects due to lactoferrin were observed in this study. Long-term neurological outcomes were not assessed in this trial.
Authors' Conclusions:
Oral lactoferrin prophylaxis reduces the incidence of late-onset sepsis in infants weighing less than 1500 g and most effective in infants weighing less than 1000 g. There is no evidence of efficacy of oral lactoferrin (given alone) in the prevention of NEC in preterm neonates.Well designed, randomized trials should address dosing, duration, type of lactoferrin (bovine or human) prophylaxis in prevention of sepsis and NEC. The effect of exclusive maternal milk feeding should be clarified.
Related Concept Videos
01:28Development of the Oral Microbiota
01:30Development of Human Microbiota