Enteral lactoferrin supplementation for prevention of sepsis and necrotizing enterocolitis in preterm infants.

Systematic review and meta-analysis of six randomized trials in preterm neonates cared for in neonatal intensive care units. The population included very low birth weight and extremely low birth weight infants from Turkey, Canada, India, Italy/New Zealand, Peru, and the United States, with enrollment usually within the first hours to days after birth.

Enteral lactoferrin supplementation was tested as oral or enteral dosing across six randomized trials in preterm infants, with regimens ranging from 100 to 250 mg/day, 200 mg/kg/day divided into 3 doses, or talactoferrin 150 mg/kg every 12 hours (300 mg/kg/day) for up to 29 days or until discharge. One active regimen combined lactoferrin 100 mg/day with Lactobacillus rhamnosus GG 6 × 10^9 CFU/mL. Comparators were placebo or standard feeding care in the included trials.

Low-quality evidence suggests enteral lactoferrin reduces late-onset sepsis and necrotizing enterocolitis in preterm infants, with no clear effect on all-cause mortality. In the probiotic-containing regimen, late-onset sepsis was 7/151 with lactoferrin plus LGG versus 29/168 with placebo, and NEC stage II or higher was 0/238 versus 14/258. Across trials, adverse effects were not observed. The review concluded that benefit appears promising but evidence quality remains limited, and optimal dose, formulation, and duration are still uncertain.

The evidence was rated low quality and was limited by risk of bias and heterogeneity across trials. Studies used different lactoferrin formulations, doses, durations, and cointerventions, which reduces comparability. Long-term outcomes, including neurodevelopment, were not established, and the small size of individual trials limits certainty about safety and efficacy.