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

We previously conducted two randomized controlled trials of bovine lactoferrin (bLF) for prevention of late-onset sepsis (LOS) in infants with a birth weight <2500g (Study 1) and <2000g (Study 2). The aim of this study was to determine the effect of bLF on prevention of culture-proven or probable LOS in infants with a birth weight <1500g from both studies, and to determine the bLF effect depending on human milk intake. Both trial designs had similar inclusion and exclusion criteria, same bLF dose (200mg/kg/day) and 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 1162g ±244g; 27.5% were <1000g. There were 33 first episodes of LOS in the bLF group and 48 in the control group (19.5% vs 28.9%). bLF had a protective effect on the risk of development LOS, Hazard Ratio (HR) 0.64 (%95CI: 0.41-0.99,p=0.048); particularly among infants <1000g, HR 0.46 (%95CI: 0.22-0.96,p=0.039) and among infants with low human milk intake, HR 0.40 (%95CI: 0.19-0.84,p=0.015). bLF supplementation protects against LOS in infants <1500g, especially among infants not receiving human milk.

[1]  J. Jacobs,et al.  Is Mother’s Own Milk Lactoferrin Intake Associated with Reduced Neonatal Sepsis, Necrotizing Enterocolitis, and Death? , 2020, Neonatology.

[2]  H. Fischer,et al.  Nutritional interventions to reduce rates of infection, necrotizing enterocolitis and mortality in very preterm infants , 2019, Pediatric Research.

[3]  Asif Hussain,et al.  Lactoferrin Supplementation to Prevent Late-Onset Sepsis in Preterm Infants: A Meta-Analysis , 2019, American Journal of Perinatology.

[4]  M. Maule,et al.  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 , 2019, American Journal of Perinatology.

[5]  P. Clarke,et al.  Enteral lactoferrin supplementation for very preterm infants: a randomised placebo-controlled trial , 2019, The Lancet.

[6]  Jialin Yu,et al.  Prophylactic lactoferrin for preventing late-onset sepsis and necrotizing enterocolitis in preterm infants , 2018, Medicine.

[7]  Raechel A. Damarell,et al.  A Systematic Review and Meta-Analysis of Human Milk Feeding and Morbidity in Very Low Birth Weight Infants , 2018, Nutrients.

[8]  D. Kaufman,et al.  Role of Lactoferrin in Neonates and Infants: An Update , 2018, American Journal of Perinatology.

[9]  M. Pammi,et al.  Enteral lactoferrin supplementation for prevention of sepsis and necrotizing enterocolitis in preterm infants. , 2017, The Cochrane database of systematic reviews.

[10]  S. Sizonenko,et al.  Lactoferrin and prematurity: a promising milk protein? , 2017, Biochemistry and cell biology = Biochimie et biologie cellulaire.

[11]  M. Meyer,et al.  Reduction in necrotizing enterocolitis and improved outcomes in preterm infants following routine supplementation with Lactobacillus GG in combination with bovine lactoferrin. , 2017, Journal of neonatal-perinatal medicine.

[12]  M. Sherman,et al.  Randomized Controlled Trial of Talactoferrin Oral Solution in Preterm Infants. , 2016, The Journal of pediatrics.

[13]  A. Janvier,et al.  The Lacuna Trial: a double-blind randomized controlled pilot trial of lactoferrin supplementation in the very preterm infant , 2016, Journal of Perinatology.

[14]  G. Kaur,et al.  Efficacy of Bovine Lactoferrin Supplementation in Preventing Late-onset Sepsis in low Birth Weight Neonates: A Randomized Placebo-Controlled Clinical Trial. , 2015, Journal of tropical pediatrics.

[15]  A. Zea-Vera,et al.  Randomized Controlled Trial of Lactoferrin for Prevention of Sepsis in Peruvian Neonates Less than 2500 g , 2015, The Pediatric infectious disease journal.

[16]  A. Zea-Vera,et al.  Lactoferrin for prevention of neonatal sepsis , 2014, BioMetals.

[17]  A. Ikinciogullari,et al.  Oral Lactoferrin to Prevent Nosocomial Sepsis and Necrotizing Enterocolitis of Premature Neonates and Effect on T-Regulatory Cells , 2014, American Journal of Perinatology.

[18]  M. Maule,et al.  Bovine lactoferrin supplementation for prevention of necrotizing enterocolitis in very-low-birth-weight neonates: a randomized clinical trial. , 2014, Early human development.

[19]  A. Zea-Vera,et al.  [Unifying criteria for late neonatal sepsis: proposal for an algorithm of diagnostic surveillance]. , 2014, Revista peruana de medicina experimental y salud publica.

[20]  W. McGuire,et al.  Lactoferrin: Antimicrobial activity and therapeutic potential. , 2013, Seminars in fetal & neonatal medicine.

[21]  K. Alfaleh.  Bovine Lactoferrin Prevents Invasive Fungal Infections in Very Low Birth Weight Infants: A Randomized Controlled Trial , 2012, Journal of clinical neonatology.

[22]  M. Maule,et al.  Bovine Lactoferrin Prevents Invasive Fungal Infections in Very Low Birth Weight Infants: A Randomized Controlled Trial , 2012, Pediatrics.

[23]  R. Lawrence,et al.  Breastfeeding: more than just good nutrition. , 2011, Pediatrics in review.

[24]  L. Cornette.  Bovine lactoferrin supplementation for prevention of late-onset sepsis in very low-birth-weight neonates: a randomized trial , 2010 .

[25]  M. Maule,et al.  Bovine lactoferrin supplementation for prevention of late-onset sepsis in very low-birth-weight neonates: a randomized trial. , 2009, JAMA.

[26]  M. R. Bentlin,et al.  Is urine interleukin-8 level a reliable laboratory test for diagnosing late onset sepsis in premature infants? , 2007, Journal of tropical pediatrics.

[27]  K. Haque.  Definitions of bloodstream infection in the newborn , 2005, Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.