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

Paolo Manzoni, Maria Angela Militello, Stefano Rizzollo, Elena Tavella, Alessandro Messina, Marta Pieretto, Elena Boano, Martina Carlino, Eleonora Tognato, Roberta Spola, Anna Perona, Milena Maria Maule, Ruben García Sánchez, Mike Meyer, Ilaria Stolfi, Lorenza Pugni, Hubert Messner, Silvia Cattani, Pasqua Maria Betta, Luigi MemoLidia Decembrino, Lina Bollani, Matteo Rinaldi, Maria Fioretti, Michele Quercia, Chryssoula Tzialla, Nicola Laforgia, Fabio Mosca, Rosario Magaldi, Michael Mostert, Daniele Farina, William Tarnow-Mordi

Research output: Contribution to journalArticle

Abstract

Background: Lactoferrin is the major antimicrobial protein in human milk. In our randomized controlled trial (RCT) of bovine lactoferrin (BLF) supplementation in preterm neonates, BLF reduced late-onset sepsis (LOS). Mother's own milk (MM) contains higher concentrations of lactoferrin than donor milk or formula, but whether BLF is more effective in infants who receive formula or donor milk is uncertain. Aim: To evaluate the incidence of LOS in preterm infants fed MM and in those fed formula and/or donor milk. Study Design: This is a (A) post hoc subgroup analysis, in our RCT of BLF, of its effects in preterm infants fed MM, with or without formula, versus those fed formula and/or donor milk (no-MM) and (B) post hoc meta-analysis, in our RCT of BLF and in the ELFIN (Enteral Lactoferrin in Neonates) RCT, of the effect of BLF in subgroups not exclusively fed MM. Results (A) Of 472 infants in our RCT, 168 were randomized to placebo and 304 were randomized to BLF. Among MM infants, LOS occurred in 22/133 (16.5%) infants randomized to placebo and in 14/250 (5.6%) randomized to BLF (relative risk or risk ratio (RR): 0.34; relative risk reduction (RRR): 0.66; 95% confidence interval (95% CI) for RR: 0.18-0.64; p < 0.0008). Among no-MM infants, LOS occurred in 7/35 (20.0%) randomized to placebo and in 2/54 (3.7%) randomized to BLF (RR: 0.19; RRR: 0.81; 95% CI for RR: 0.16-0.96; p = 0.026). In multivariable logistic regression analysis, there was no interaction between BLF treatment effect and type of feeding (p = 0.628). (B) In 1,891 infants not exclusively fed MM in our RCT of BLF and in the ELFIN RCT, BLF reduced the RR of LOS by 18% (RR: 0.82; 95% CI: 0.71-0.96; p = 0.01). Conclusion: Adequately powered studies should address the hypothesis that BLF is more effective in infants fed formula or donor milk than those fed MM. Such studies should evaluate whether a specific threshold of total lactoferrin intake can be identified to protect such patients from LOS.

Original languageEnglish
Pages (from-to)S120-S125
JournalAmerican Journal of Perinatology
Volume36
DOIs
Publication statusPublished - Jan 1 2019

Keywords

  • Candida
  • formula milk
  • human milk
  • infection
  • lactoferrin
  • preterm infants
  • sepsis
  • VLBW neonates

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Obstetrics and Gynaecology

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    Manzoni, P., Militello, M. A., Rizzollo, S., Tavella, E., Messina, A., Pieretto, M., Boano, E., Carlino, M., Tognato, E., Spola, R., Perona, A., Maule, M. M., García Sánchez, R., Meyer, M., Stolfi, I., Pugni, L., Messner, H., Cattani, S., Betta, P. M., ... Tarnow-Mordi, W. (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. American Journal of Perinatology, 36, S120-S125. https://doi.org/10.1055/s-0039-1691807