ELFIN

A multi-centre randomised placebo-controlled trial of prophylactic enteral supplementation with bovine lactoferrin to prevent late-onset invasive infection in very preterm or very low birth weight infants.

Trial started: 2013  Trial ended: 2017 

Summary

Objectives

To determine whether or not enteral supplementation with bovine lactoferrin reduces the risk of late-onset infection (acquired >?72 hours after birth) and other morbidity and mortality in very preterm infants.

Methods

A randomised, placebo-controlled, parallel-group trial conducted in UK neonatal units between May 2014 and September 2017. Infants born at <32 weeks’ gestation and aged <72 hours at trial enrolment were randomised to receive either enteral bovine lactoferrin (150?mg/kg/day; maximum 300?mg/day) or sucrose 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.

Outcome measures

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.

Adapted from: Griffiths J, Jenkins P, Vargova M, et al. Enteral lactoferrin to prevent infection for very preterm infants: the ELFIN RCT. Health Technology Assessment. 2018;22(74). https://doi.org/10.3310/hta22740. © Queen's Printer and Controller of HMSO 2018. Adapted for presentation on this website.