Lactoferrin as a nutritional enteral supplement has emerged as a novel preventative
therapy against serious
infections in preterm infants, although neonatal studies have demonstrated variable results, in part due to the lack of pharmacokinetic data and differences in the products tested. We conducted a prospective, dose escalation (100, 200, and 300 mg·kg-1·day-1) safety study of bovine
lactoferrin (Glanbia Nutritionals, USA) dissolved in sterile water (100 mg·mL-1) for 30 days in preterm infants with
birth weight <1500 g. Safety related to adverse events (AEs), tolerability, and exposure-response of
lactoferrin was assessed. We enrolled 31 patients [10, 10, and 11 patients, for the
lactoferrin treatment groups (100, 200, and 300 mg·kg-1·day-1, respectively)] over a 10-month period. No AEs related to the study
solution occurred, and
lactoferrin was tolerated by each group. During
lactoferrin supplementation, one
bloodstream infection occurred in each group, but there were no incidences of
urinary tract infections and no cases of
necrotizing enterocolitis. Postnatal cytomegalovirus acquisition was detected in the group treated with 200 mg·kg-1·day-1 (n = 2). There were no adverse effects on hepatic, renal, or hematologic function. All of the patients survived to discharge. Bovine
lactoferrin at doses up to 300 mg·kg-1·day-1 is safe in preterm infants. Future studies examining higher doses of
lactoferrin, length of treatment, and potency of different products will aid in determining the optimal approach for the use of
lactoferrin to prevent
infections in preterm infants.