Enteral lactoferrin supplementation for very preterm infants: a randomised placebo-controlled trial

Design: randomised, placebo-controlled, multicenter, parallel-group trial with masking of participants, caregivers, and outcome assessors. Participants: very preterm infants born <32 weeks gestation, recruited from 37 UK neonatal units; randomised within 72 h of birth; exclusions included severe congenital anomaly, anticipated enteral fasting >14 days, or no realistic prospect of survival.

Bovine lactoferrin; 150 mg/kg/day (max 300 mg/day); administered enterally once daily from randomisation (within 72 h of birth) until 34 weeks postmenstrual age; mixture prepared by dissolving lactoferrin powder in 4 mL sterile water and 1 mL expressed breast milk or formula to 75 mg/mL; administered via gastric tube with feeds.

Enteral bovine lactoferrin at 150 mg/kg/day (max 300 mg/day) did not reduce late-onset infection or major morbidity/mortality in very preterm infants. Primary outcome: 316/1093 (29%) vs 334/1089 (31%); adjusted RR 0.95 (95% CI 0.86–1.04; p=0.233). No significant differences in all-cause mortality, NEC, retinopathy of prematurity, bronchopulmonary dysplasia, or the composite outcome of infection, major morbidity, or mortality. Serious adverse events were similar across groups (16 vs 10; two possibly related to the trial). Authors conclude routine enteral bovine lactoferrin supplementation is not supported for preventing late-onset infection or related morbidity/mortality in very preterm infants.

Primary outcome combined clinically suspected and microbiologically confirmed late-onset infection, which may affect the accuracy of infection classification.