Researchers undertook this large randomized controlled trial to enhance the validity and applicability of the evidence from previous trials suggesting preventive effects of supplementing the enteral diet of very preterm infants with lactoferrin, an antimicrobial protein processed from cow's milk, against infections and associated complications. Findings do not suggest enteral supplementation with bovine lactoferrin as effective in reducing the risk of late-onset infection in very preterm infants. Data thus provide no support to its routine use in very preterm infants to prevent late-onset infection and associated morbidity or mortality.

• In 37 UK hospitals, researchers recruited very preterm infants born before 32 weeks' gestation and younger than 72 h at randomization in this randomized placebo-controlled trial.
• They excluded the infants if they showed presence of a severe congenital anomaly, anticipated enteral fasting for longer than 14 days, or no realistic prospect of survival.
• Either enteral bovine lactoferrin (150 mg/kg per day; maximum 300 mg/day; lactoferrin group) or sucrose (same dose; control group) once daily until 34 weeks' postmenstrual age was randomly provided (1:1) to eligible infants.
• Web-based randomization minimized for recruitment site, gestation (completed weeks), sex, and single vs multifetal pregnancy.
• Group assignment was masked to parents, caregivers, and outcome assessors.
• Microbiologically confirmed or clinically suspected late-onset infection (occurring >72 h after birth) was assessed as the primary outcome; this was assessed in all participants for whom primary outcome data was available by calculating the relative risk ratio with 95% CI between the two groups. 

• Between May 7, 2014, and Sept 28, 2017, 2203 participants were recruited; of these, 1099 were assigned to the lactoferrin group and 1104 to the control group.
• Withdrawing or unconfirmed consent for 4 infants left 1098 infants in the lactoferrin group and 1101 in the sucrose group.
• For the modified intention-to-treat analyses, they had primary outcome data for 2182 infants (1093 [99·5%] of 1098 in the lactoferrin group and 1089 [99·0] of 1101 in the control group) available for inclusion.
• A late-onset infection was noted in 316 (29%) of 1093 infants in the intervention group vs 334 (31%) of 1089 in the control group.
• For minimization factors, the risk ratio adjusted was 0·95 (95% CI 0·86–1·04; p=0·233).
• Serious adverse events were encountered in 16 infants in the lactoferrin group and 10 infants in the control group during the trial.
• Possible relation to the trial intervention was noted of two events in the lactoferrin group (one case of blood in stool and one death after intestinal perforation).