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Updated: Dec 10, 2025

A Neonatal Imaging Model of Gram-Negative Bacterial Sepsis
Published on: August 12, 2020
Lactoferrin Expression Is Not Associated with Late-Onset Sepsis in Very Preterm Infants
Tobias Strunk1,2,3, Julie Elizabeth Hibbert4,5, Dorota Doherty5
1Neonatal Directorate, King Edward Memorial Hospital, Perth, Washington, Australia, tobiasstrunk@yahoo.de.
Insights
Endogenous lactoferrin levels did not differ between preterm infants with or without late-onset sepsis (LOS). This suggests lactoferrin may not be a reliable biomarker or preventive agent for LOS in this population.
Area of Science:
- Neonatal Medicine
- Immunology
- Biochemistry
Background:
- Preterm infants face a high risk of late-onset sepsis (LOS).
- Lactoferrin, an antimicrobial protein in breast milk and bodily fluids, is a potential preventive agent.
- Clinical trials have explored bovine lactoferrin supplementation to reduce LOS.
Purpose of the Study:
- To measure lactoferrin levels in preterm infants during their first month of life.
- To compare lactoferrin levels in infants with and without LOS.
- To assess the in vitro release of lactoferrin in response to immune stimuli.
Main Methods:
- Serial blood, stool, and breast milk samples were collected from preterm and term infants.
- Lactoferrin levels were quantified using immunoassay.
- Peripheral blood's capacity to release lactoferrin was tested against Staphylococcus epidermidis and other stimuli.
Main Results:
- Plasma lactoferrin was higher in cord and day 1 blood, decreasing over the first month.
- Lactoferrin levels were similar in term infants and preterm infants with or without LOS.
- S. epidermidis-induced lactoferrin release was lower after sepsis onset.
Conclusions:
- Endogenous lactoferrin levels do not appear to influence LOS risk in preterm infants.
- Findings align with recent trials showing no benefit from bovine lactoferrin supplementation for LOS prevention.
Background:
Preterm infants are at a high risk of developing late-onset sepsis (LOS). Lactoferrin is one of the most abundant endogenous antimicrobial proteins expressed in breast milk, stools, and blood, and a candidate for preventive intervention. Large clinical trials have recently investigated whether enteral supplementation with bovine lactoferrin reduces LOS.
Aim:
To characterize lactoferrin levels in preterm infants with and without LOS during the first month of life.
Methods:
Very preterm and term infants were recruited and serial biosamples collected during the first month of life. Lactoferrin levels were determined by immunoassay in cord blood and peripheral blood on days 1, 7, 14, 21, and 28; in the stools on days 1 and 28; and in the mother's breast milk on days 7 and 21. Furthermore, we assessed the capacity of the peripheral blood to release lactoferrin in response to an in vitro challenge with live Staphylococcus epidermidis, lipopolysaccharide, and fibroblast-stimulating lipopeptide 1.
Results:
Plasma lactoferrin levels were higher in cord blood and day 1 peripheral blood and declined during the first month of life. Plasma lactoferrin levels were similar in term infants and in preterm infants with (n = 32) and without LOS (n = 53). S. epidermidis-induced lactoferrin levels were lower following the sepsis episode.
Conclusions:
Endogenous lactoferrin expression in preterm infants does not appear to affect their risk of developing LOS. These findings are in line with the lack of benefit recently observed in large trials of enteral supplementation with bovine lactoferrin to prevent LOS.

