Please note our website will be undergoing maintenance on Tuesday, May 28, 2024. e-Commerce transactions and new registrations will be temporarily unavailable during this time. We apologize for any inconvenience this may cause.

Cookies Notification

We use cookies to improve your website experience. To learn about our use of cookies and how you can manage your cookie settings, please see our Cookie Policy.
×

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

Abstract

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.

Résumé

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.

Get full access to this article

View all available purchase options and get full access to this article.

References

Akin I., Atasay B., Dogu F., Okulu E., Arsan Karatas H.D., et al. 2014. Oral lactoferrin to prevent nosocomial sepsis and necrotizing enterocolitis of premature neonates and effect on T-regulatory cells. Am. J. Perinatol. 31(12): 1111–1120.
Barrington K.J., Assaad M.-A., and Janvier A. 2016. The Lacuna Trial: a double-blind randomized controlled pilot trial of lactoferrin supplementation in the very preterm infant. J. Perinatol. 36(8): 666–669.
Bührer C., Fischer H.S., and Wellmann S. 2020. Nutritional interventions to reduce rates of infection, necrotizing enterocolitis and mortality in very preterm infants. Pediatr. Res. 87(2): 371–377.
Dai J.Z. and Xie C. 2015. The effect of lactoferrin supplementation combining Lactobacillus rhamnosus for prevention of late-onset sepsis in premature neonates. China Pract. Med. 10: 98–100.
Embleton N.D., Berrington J.E., McGuire W., Stewart C.J., and Cummings S.P. 2013. Lactoferrin: antimicrobial activity and therapeutic potential. Semin. Fetal Neonatal Med. 18(3): 143–149.
Griffiths J., Jenkins P., Vargova M., Bowler U., Juszczak E., King A., et al. 2019. Enteral lactoferrin supplementation for very preterm infants: a randomised placebo-controlled trial. Lancet, 393(10170): 423–433.
Haque K.N. 2005. Definitions of bloodstream infection in the newborn. Pediatr. Crit. Care Med. 6(3 Suppl): S45–S49.
He Y., Cao L., and Yu J. 2018. Prophylactic lactoferrin for preventing late-onset sepsis and necrotizing enterocolitis in preterm infants: a PRISMA-compliant systematic review and meta-analysis. Medicine (Baltimore), 97(35): e11976.
Kaur G. and Gathwala G. 2015. Efficacy of bovine lactoferrin supplementation in preventing late- onset sepsis in low birth weight neonates: a randomized placebo-controlled clinical trial. J. Trop. Pediatr. 61(5): 370–376.
Lawrence R.M. and Lawrence R.A. 2011. Breastfeeding: more than just good nutrition. Pediatr. Rev. 32(7): 267–280.
Liu Y.H., Guan H.S., and Liang G.J. 2016. The effect of lactoferrin on low birth weight neonates during hospitalization. MCH Care China, 31: 4464–4465.
Manzoni P., Rinaldi M., Cattani S., Pugni L., Romeo M.G., Messner H., et al. 2009. Bovine lactoferrin supplementation for prevention of late-onset sepsis in very low-birth-weight neonates: a randomized trial. JAMA, 302(13): 1421–1428.
Manzoni P., Stolfi I., Messner H., Cattani S., Laforgia N., Romeo M.G., et al. 2012. Bovine lactoferrin prevents invasive fungal infections in very low birth weight infants: a randomized controlled trial. Pediatrics, 129(1): 116–123.
Manzoni P., Meyer M., Stolfi I., Rinaldi M., Cattani S., Pugni L., et al. 2014. Bovine lactoferrin supplementation for prevention of necrotizing enterocolitis in very-low-birth-weight neonates: a randomized clinical trial. Early Hum. Dev. 90: S60–S65.
Manzoni P., Dall’Agnola A., Tomé D., Kaufman D., Tavella E., Pieretto M., et al. 2018. Role of lactoferrin in neonates and infants: an update. Am. J. Perinatol. 35(6): 561–565.
Manzoni P., Militello M.A., Rizzollo S., Tavella E., Messina A., Pieretto M., et al. 2019. Is lactoferrin more effective in reducing late-onset sepsis in preterm neonates fed formula than in those receiving mother’s own milk? Secondary analyses of two multicenter randomized controlled trials. Am. J. Perinatol. 36(S 02): S120–S125.
Meyer M.P. and Alexander T. 2017. Reduction in necrotizing enterocolitis and improved outcomes in preterm infants following routine supplementation with Lactobacillus GG in combination with bovine lactoferrin. J. Neonatal Perinatal Med. 10(3): 249–255.
Miller J., Tonkin E., Damarell R.A., McPhee A., Suganuma M., Suganuma H., et al. 2018. A systematic review and meta-analysis of human milk feeding and morbidity in very low birth weight infants. Nutrients, 10(6): 707.
Ochoa T.J. and Sizonenko S.V. 2017. Lactoferrin and prematurity: a promising milk protein? Biochem. Cell Biol. 95(1): 22–30.
Ochoa T.J., Zegarra J., Cam L., Llanos R., Pezo A., Cruz K., et al. 2015. Randomized controlled trial of lactoferrin for prevention of sepsis in Peruvian neonates less than 2500 g. Pediatr. Infect. Dis. J. 34(6): 571–576.
Ochoa T.J., Zegarra J., Bellomo S., Carcamo C.P., Cam L., Castañeda A., et al. 2020a. Randomized controlled trial of bovine lactoferrin for prevention of sepsis and neurodevelopment impairment in infants weighing less than 2000 Grams. J. Pediatr. 219: 118–125.e5.
Ochoa T.J., Mendoza K., Carcamo C., Zegarra J., Bellomo S., Jacobs J., et al. 2020b. Is mother’s own milk lactoferrin intake associated with reduced neonatal sepsis, necrotizing enterocolitis, and death? Neonatology, 117: 167–174.
Pammi M. and Suresh G. 2017. Enteral lactoferrin supplementation for prevention of sepsis and necrotizing enterocolitis in preterm infants. Cochrane Database Syst. Rev. 6: CD007137.
Razak A. and Hussain A. 2019. Lactoferrin supplementation to prevent late-onset sepsis in preterm infants: a meta-analysis. Am. J. Perinatol.
Sherman M.P., Adamkin D.H., Niklas V., Radmacher P., Sherman J., Wertheimer F., et al. 2016. Randomized controlled trial of talactoferrin oral solution in preterm infants. J. Pediatr. 175: 68–73.
Tang J.P., Sun H.Q., and Zheng Y.H. 2017. Randomized control trial of lactoferrin for prevention of late onset sepsis in premature infants. MCH Care China, 32: 1223–1225.
Turin C.G., Zea-Vera A., Pezo A., Cruz K., Zegarra J., Bellomo S., et al. 2014. Lactoferrin for prevention of neonatal sepsis. Biometals, 27(5): 1007–1016.
Zea-Vera A., Turin C.G., and Ochoa T.J. 2014. [Unifying criteria for late neonatal sepsis: proposal for an algorithm of diagnostic surveillance.] Rev. Peru. Med. Exp. Salud Publ. 31(2): 358–363.

Information & Authors

Information

Published In

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

History

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

Notes

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.

Permissions

Request permissions for this article.

Key Words

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

Mots-clés

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

Authors

Affiliations

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.

Notes

Copyright remains with the author(s) or their institution(s). Permission for reuse (free in most cases) can be obtained from copyright.com.

Metrics & Citations

Metrics

Other Metrics

Citations

Cite As

Export Citations

If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download.

Cited by

1. Time to Kill and Time to Heal: The Multifaceted Role of Lactoferrin and Lactoferricin in Host Defense
2. Effect of Lactoferrin on Clinical Outcomes of Hospitalized Patients with COVID-19: The LAC Randomized Clinical Trial
3. Potential of Lactoferrin in the Treatment of Lung Diseases
4. Lactoferrin extends its reach into South America1
5. Applications of gut microbiota in patients with hematopoietic stem-cell transplantation

View Options

Get Access

Login options

Check if you access through your login credentials or your institution to get full access on this article.

Subscribe

Click on the button below to subscribe to Biochemistry and Cell Biology

Purchase options

Purchase this article to get full access to it.

Restore your content access

Enter your email address to restore your content access:

Note: This functionality works only for purchases done as a guest. If you already have an account, log in to access the content to which you are entitled.

View options

PDF

View PDF

Full Text

View Full Text

Media

Media

Other

Tables

Share Options

Share

Share the article link

Share on social media