Dose Escalation Study of Bovine Lactoferrin in Preterm Infants: Getting the Dose Right.

Lactoferrin as a nutritional enteral supplement has emerged as a novel preventative therapy against serious infections in preterm infants, though neonatal studies have demonstrated variable results in part due to the lack of pharmacokinetic data and differences in products. We conducted a prospective, dose escalation (100, 200, and 300 mg/kg/day) safety study of bovine lactoferrin (Glanbia Nutritionals, USA) dissolved in sterile water (100 mg/ml) for 30 days in preterm infants <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 respectively) over a 10-month period. No study solution related AEs occurred and lactoferrin was tolerated in each group. During lactoferrin supplementation one bloodstream infection occurred in each group, no urinary tract infections and no cases of necrotizing enterocolitis. Postnatal cytomegalovirus acquisition was detected in the 200 mg/kg/day group (n=2). There were no adverse effects on hepatic, renal, or hematologic function. All patients survived to discharge. Bovine lactoferrin at doses up to 300 mg/kg/day is safe in preterm infants. Future studies examining higher lactoferrin dosing, length of treatment, and potency of different products will aid in determining the optimal approach of lactoferrin in infection prevention.