Paolo Manzoni1,2, Maria Angela Militello1, Stefano Rizzollo1, Elena Tavella2, Alessandro Messina2, Marta Pieretto2, Elena Boano2, Martina Carlino2, Eleonora Tognato1, Roberta Spola1, Anna Perona1, Milena Maria Maule3, Ruben García Sánchez4, Mike Meyer5, Ilaria Stolfi6, Lorenza Pugni7, Hubert Messner8, Silvia Cattani9, Pasqua Maria Betta10, Luigi Memo11, Lidia Decembrino12, Lina Bollani12, Matteo Rinaldi13, Maria Fioretti14, Michele Quercia15, Chryssoula Tzialla12, Nicola Laforgia14, Fabio Mosca7,16, Rosario Magaldi13, Michael Mostert17, Daniele Farina1, William Tarnow-Mordi18. 1. Division of Pediatrics and Neonatology, Department of Maternal, Neonatal, and Infant Medicine, Nuovo Ospedale Degli Infermi, Biella, Italy. 2. Neonatology and NICU, Sant'Anna Hospital, AOU Città della Salute e della Scienza, Torino, Italy. 3. Cancer Epidemiology Unit, Department of Medical Sciences, University of Turin, Torino, Italy. 4. Department of Neonatology and NICU, Complejo Asistencial Universitario de Salamanca, Salamanca, Spain. 5. Department of Neonatology and NICU, Middlemore Hospital, Auckland, New Zealand. 6. Department of Neonatology, Azienda Ospedaliera Universitaria Policlinico Umberto I, Roma, Italy. 7. Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, NICU, Milan, Italy. 8. Department of Neonatology and NICU, Ospedale Regionale, Bolzano/Bozen, Italy. 9. NICU, University of Modena and Reggio Emilia, Modena, Italy. 10. NICU, Azienda Ospedaliera Universitaria Policlinico di Catania, Catania, Italy. 11. U.O.C. di Pediatria e Patologia Neonatale, Ospedale San Martino, Belluno, Italy. 12. UOC Neonatologia e Terapia Intensiva, IRCCS Policlinico San Matteo, Pavia, Italy. 13. Department of Neonatology, Ospedali Riuniti, Foggia, Italy. 14. Terapia Intensiva Neonatale, Ospedale Monaldi-Azienda Ospedaliera dei Colli, Napoli, Italy. 15. Neonatology and Neonatal Intensive Care Unit, Department of Biomedical Sciences and Human Oncology, University of Bari, Bari, Italy. 16. Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy. 17. Department of Pediatrics, University of Turin, Torino, Italy. 18. NHMRC Clinical Trials Centre, University of Sydney, Sydney, New South Wales, Australia.
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 toplacebo 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. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
RCT Entities:
BACKGROUND:Lactoferrin is the major antimicrobial protein in human milk. In our randomized controlled trial (RCT) of bovinelactoferrin (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. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Authors: Michael P Meyer; Sharon S W Chow; Jane Alsweiler; David Bourchier; Roland Broadbent; David Knight; Adrienne M Lynn; Harshad Patel Journal: Front Pediatr Date: 2020-04-07 Impact factor: 3.418