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Effect of bovine lactoferrin on prevention of late-onset sepsis in infants <1500 g: a pooled analysis of individual patient data from two randomized controlled trials

Publication: Biochemistry and Cell Biology
15 September 2020


We previously conducted two randomized controlled trials with bovine lactoferrin (bLF) for the prevention of late-onset sepsis (LOS) in infants with a birth weight <2500 g (Study 1) and <2000 g (Study 2). The aim of this study was to determine the preventative effects of bLF on culture-proven or probable LOS in infants with a birth weight <1500 g from both studies, and to determine the effect of bLF in relation to intake of human milk. Both trial designs had similar inclusion and exclusion criteria, the same dose of bLF [200 mg·(kg body mass)–1·day–1], and used the same control (maltodextrin). We fitted multivariate Cox regression models to estimate the effect of bLF on the risk of development of the composite outcome, adjusting for covariates. We included 335 neonates with a mean birth weight of 1162 ± 244 g; 27.5% were <1000 g. There were 33 first episodes of LOS in the bLF treatment group and 48 in the control group (19.5% vs. 28.9%). bLF had a protective effect on the risk of development of LOS [hazard ratio (HR) = 0.64; %95 CI = 0.41–0.99; p = 0.048]; particularly among infants weighing <1000 g [HR = 0.46; %95 CI = 0.22–0.96; p = 0.039] and infants with a low intake of human milk [HR = 0.40; %95 CI = 0.19–0.84; p = 0.015]. Therefore, bLF supplementation protects infants <1500 g from LOS, particularly those infants not receiving human milk.


Les auteurs ont précédemment mené deux essais contrôlés randomisés sur la lactoferrine bovine (bLF) pour la prévention de la septicémie tardive chez les nourrissons d’un poids à la naissance inférieur à 2500 g (étude 1) et inférieur à 2000 g (étude 2). L’objectif de cette étude était de déterminer l’effet de la bLF sur la prévention de la septicémie tardive probable ou prouvée par culture chez les nourrissons d’un poids à la naissance inférieur à 1500 g dans les deux études, et de déterminer l’effet de la bLF en fonction de la consommation de lait humain. Les deux devis expérimentaux comportaient des critères d’inclusion et d’exclusion similaires, la même dose de bLF [200 mg·(kg de masse corporelle)–1·jour–1] et le même contrôle (maltodextrine). Ils ont ajusté des modèles de régression de Cox à plusieurs variables pour estimer l’effet de la bLF sur le risque de développement du résultat composite, en tenant compte des covariables. Ils ont inclus 335 nouveau-nés ayant un poids moyen à la naissance de 1162 ± 244 g; 27,5 % pesaient moins de 1000 g. Trente-trois premiers épisodes de septicémie tardive sont survenus dans le groupe bLF et 48 dans le groupe de contrôle (19,5 % contre 28,9 %). La bLF exerçait un effet protecteur sur le risque de développement de la septicémie tardive, avec un rapport de risque de 0,64 (% 95 IC = 0,41–0,99; p = 0,048), particulièrement chez les nourrissons de moins de 1000 g, avec un rapport de risque de 0,46 (% 95 IC = 0,22–0,96; p = 0,039) et chez les nourrissons à faible consommation de lait humain, avec un rapport de risque de 0,40 (% 95 IC = 0,19–0,84 ; p = 0,015). La supplémentation en bLF protège les nourrissons de moins 1500 g contre la septicémie tardive, en particulier les nourrissons qui ne reçoivent pas de lait humain.

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Published In

cover image Biochemistry and Cell Biology
Biochemistry and Cell Biology
Volume 99Number 1February 2021
Pages: 14 - 19


Received: 7 February 2020
Accepted: 17 August 2020
Accepted manuscript online: 15 September 2020
Version of record online: 15 September 2020


This Article is one of a selection of papers from the 14th International Conference on Lactoferrin Structure, Function, and Applications, held in Lima, Peru, 4–8 November 2019.


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Key Words

  1. lactoferrin
  2. sepsis
  3. neonatal
  4. randomized controlled trial


  1. lactoferrine
  2. septicémie
  3. néonatal
  4. essai contrôlé randomisé



Theresa Ochoa [email protected]
Facultad de Medicina, Universidad Peruana Cayetano Heredia, Lima, Peru.
School of Public Health, University of Texas Health Science Center at Houston, Houston, Texas, USA.
Doctoral School of Biomedial Sciences, KU Leuven, Belgium.
Sebastian Loli
Facultad de Salud Pública y Administración, Universidad Peruana Cayetano Heredia, Lima, Peru.
Karina Mendoza
Facultad de Salud Pública y Administración, Universidad Peruana Cayetano Heredia, Lima, Peru.
Cesar Carcamo
Facultad de Salud Pública y Administración, Universidad Peruana Cayetano Heredia, Lima, Peru.
Sicilia Bellomo
Facultad de Medicina, Universidad Peruana Cayetano Heredia, Lima, Peru.
Hospital Cayetano Heredia, Lima, Peru.
Luis Cam
Hospital Nacional Alberto Sabogal, Lima, Peru.
Anne Castaneda
Hospital Nacional Guillermo Almenara, Lima, Peru.
Miguel Campos
Facultad de Ciencias y Filosofia, Universidad Peruana Cayetano Heredia, Lima, Peru.
Jan Jacobs
Department of Microbiology and Immunology, KU Leuven, Belgium.
Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
Veerle Cossey
Department of Development and Regeneration, KU Leuven, Belgium.
Jaime Zegarra
Facultad de Medicina, Universidad Peruana Cayetano Heredia, Lima, Peru.
Hospital Cayetano Heredia, Lima, Peru.


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