Randomized Controlled Trial of Talactoferrin Oral Solution in Preterm Infants

Sherman, Michael P.; Adamkin, David H.; Niklas, Victoria; Radmacher, Paula G.; Sherman, J. Daniel; Wertheimer, Fiona; Petrak, Karel

doi:10.1016/j.jpeds.2016.04.084

Cited by 42 publications

(27 citation statements)

References 21 publications

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“…21 The only study evaluating human lactoferrin supplementation in very low birth weight infants reported lower rates of hospitalacquired infections with lactoferrin versus placebo (17% versus 33%; p < 0.04), but the study was underpowered to identify significant differences in outcomes between the two groups. 22 A recent Cochrane review that included six RCTs evaluating lactoferrin supplementation in preterm neonates concluded that lactoferrin supplementation, with or without probiotics, decreased late-onset sepsis (risk ratio [RR], 0.59; p = 0.008) and NEC (RR, 0.40; p = 0.02) with no adverse effects, but the available evidence was graded as ''low'' or ''low to moderate'' quality. 23 Further studies are needed to compare the different types of lactoferrin (human or bovine) to determine optimal dosing regimens and to assess longterm outcomes.…”

mentioning

confidence: 99%

Clinical Studies of Lactoferrin in Neonates and Infants: An Update

Manzoni

2019

Breastfeeding Medicine

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confidence: 99%

Clinical Studies of Lactoferrin in Neonates and Infants: An Update

Manzoni

2019

Breastfeeding Medicine

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“…The Cochrane review by Pammi and Suresh 40 identified six completed randomised controlled trials (RCTs), involving 1071 participants in total. [41][42][43][44][45][46] Meta-analyses suggest that enteral supplementation with lactoferrin reduces the incidence of late-onset invasive infection by about 40%; the effect size is similar whether infants are fed predominantly human milk or formula milk. The incidence of NEC is decreased by about 60%.…”

Section: Existing Evidencementioning

confidence: 99%

Enteral lactoferrin to prevent infection for very preterm infants: the ELFIN RCT

Griffiths

Jenkins

Vargova

et al. 2018

Health Technol Assess

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Background Infections acquired in hospital are an important cause of morbidity and mortality in very preterm infants. Several small trials have suggested that supplementing the enteral diet of very preterm infants with lactoferrin, an antimicrobial protein processed from cow’s milk, prevents infections and associated complications. Objective To determine whether or not enteral supplementation with bovine lactoferrin (The Tatua Cooperative Dairy Company Ltd, Morrinsville, New Zealand) reduces the risk of late-onset infection (acquired > 72 hours after birth) and other morbidity and mortality in very preterm infants. Design Randomised, placebo-controlled, parallel-group trial. Randomisation was via a web-based portal and used an algorithm that minimised for recruitment site, weeks of gestation, sex and single versus multiple births. Setting UK neonatal units between May 2014 and September 2017. Participants Infants born at < 32 weeks’ gestation and aged < 72 hours at trial enrolment. Interventions Eligible infants were allocated individually (1 : 1 ratio) to receive enteral bovine lactoferrin (150 mg/kg/day; maximum 300 mg/day) or sucrose (British Sugar, Peterborough, UK) placebo (same dose) once daily from trial entry until a postmenstrual age of 34 weeks. Parents, caregivers and outcome assessors were unaware of group assignment. Outcomes Primary outcome – microbiologically confirmed or clinically suspected late-onset infection. Secondary outcomes – microbiologically confirmed infection; all-cause mortality; severe necrotising enterocolitis (NEC); retinopathy of prematurity (ROP); bronchopulmonary dysplasia (BPD); a composite of infection, NEC, ROP, BPD and mortality; days of receipt of antimicrobials until 34 weeks’ postmenstrual age; length of stay in hospital; and length of stay in intensive care, high-dependency and special-care settings. Results Of 2203 enrolled infants, primary outcome data were available for 2182 infants (99%). In the intervention group, 316 out of 1093 (28.9%) infants acquired a late-onset infection versus 334 out of 1089 (30.7%) infants in the control group [adjusted risk ratio (RR) 0.95, 95% confidence interval (CI) 0.86 to 1.04]. There were no significant differences in any secondary outcomes: microbiologically confirmed infection (RR 1.05, 99% CI 0.87 to 1.26), mortality (RR 1.05, 99% CI 0.66 to 1.68), NEC (RR 1.13, 99% CI 0.68 to 1.89), ROP (RR 0.89, 99% CI 0.62 to 1.28), BPD (RR 1.01, 99% CI 0.90 to 1.13), or a composite of infection, NEC, ROP, BPD and mortality (RR 1.01, 99% CI 0.94 to 1.08). There were no differences in the number of days of receipt of antimicrobials, length of stay in hospital, or length of stay in intensive care, high-dependency or special-care settings. There were 16 reports of serious adverse events for infants in the lactoferrin group and 10 for infants in the sucrose group. Conclusions Enteral supplementation with bovine lactoferrin does not reduce the incidence of infection, mortality or other morbidity in very preterm infants. Future work Increase the precision of the estimates of effect on rarer secondary outcomes by combining the data in a meta-analysis with data from other trials. A mechanistic study is being conducted in a subgroup of trial participants to explore whether or not lactoferrin supplementation affects the intestinal microbiome and metabolite profile of very preterm infants. Trial registration Current Controlled Trials ISRCTN88261002. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 74. See the NIHR Journals Library website for further project information. This trial was also sponsored by the University of Oxford, Oxford, UK. The funder provided advice and support and monitored study progress but did not have a role in study design or data collection, analysis and interpretation.

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“…Among these is lactoferrin (LF), a glycoprotein with anti-infective and immune-modulating effects [4][5][6]. There is currently high interest in studying the effects of Ochoa bovine LF supplementation on the prevention of neonatal sepsis and NEC [7][8][9][10][11][12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Is Mother’s Own Milk Lactoferrin Intake Associated with Reduced Neonatal Sepsis, Necrotizing Enterocolitis, and Death?

et al. 2020

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Introduction: Lactoferrin (LF) is a protective protein present in milk with anti-infective and immune-modulating properties. Objectives: The aim of this study was to determine the association of maternal LF intake and mother's own milk intake in the first 10 days of life on the prevention of late-onset sepsis (LOS), necrotizing enterocolitis (NEC), or death in the first 8 weeks of life in newborns with a birth weight < 2,000 g. Methods: A retrospective cohort study was conducted, with the exposure being the consumption of mother's own LF and mother's own milk in the first 10 days of life, and the outcome being LOS, NEC, or death during days 11 and 56 of life, analyzed by Cox regression. Results: Two hundred and ninety-nine infants were enrolled, including 240 with human LF intake information. The average daily human LF intake over days 4-10 of life was 283 mg/kg/day (IQR 114-606 mg/ kg/day). The hazard ratio (HR) of mother's own milk LF intake ≥100 mg/kg/day in days 4-10 for LOS, NEC, or death was 0.297 (95% CI 0.156-0.568, p < 0.001); the adjusted HR was 0.752 (95% CI 0.301-1.877, p = 0.541). The adjusted HR of mother's own milk cumulative intake (days 4-10) of 54-344 mL/kg (25-75 quartiles) for LOS, NEC, or death was 0.414 (95% CI 0.196-0.873, p = 0.02). Infants who developed an event (LOS, NEC, or death) had significantly less median daily human LF intake than those that did not (89 vs. 334 mg/ kg/day, respectively, p < 0.0001). Conclusion: Consumption of higher amounts of mother's own milk in the first days of life is associated with less infection, NEC, and death. Early human milk intake should be strongly encouraged in all newborns.

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Randomized Controlled Trial of Talactoferrin Oral Solution in Preterm Infants

Cited by 42 publications

References 21 publications

Clinical Studies of Lactoferrin in Neonates and Infants: An Update

Clinical Studies of Lactoferrin in Neonates and Infants: An Update

Enteral lactoferrin to prevent infection for very preterm infants: the ELFIN RCT

Is Mother’s Own Milk Lactoferrin Intake Associated with Reduced Neonatal Sepsis, Necrotizing Enterocolitis, and Death?

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