Human milk alone has insufficient nutrients to meet preterm infant requirements and a multi-nutrient fortifier, bovine milk-based (BMBF) or human milk-based (HMBF), is recommended. As the nutrient composition of BMBF and HMBF differs [1, 2], the biochemical effects may also differ; these differences have not yet been reported. This secondary analysis of a randomized controlled trial comparing BMBF and HMBF examined the biochemical response to the different fortifiers in preterm infants which were hypothesized to differ given different intakes of protein and iron [3].

Infants born <1250 g who met eligibility criteria for the Optimizing Mothers’ Milk for Preterm Infants (OptiMoM) trial (NCT02137473) were studied [3]. Following informed consent, infants were provided mother’s milk first then pasteurized donor milk as required and had BMBF or HMBF added to human milk feeds in a blinded fashion depending on their randomization. The HMBF group received Prolact+4 and +6 (Prolacta Bioscience, City of Industry, USA) commencing at 100 mL/kg/day (81 kcal/dL, 2.2 g/dL protein, 0.1 mg/dL iron) and 140 mL/kg/day (88 kcal/dL, 2.7 g/dL protein, 0.2 mg/dL iron), respectively. In the BMBF group, 0.4 g/dL intact protein modular (Beneprotein, Nestle, Minneapolis, USA) was added to donor milk and Similac Human Milk Fortifier (Abbott Nutrition, Columbus, USA) 1:50 and 1:25 commenced at 100 mL/kg/day (72 kcal/dL, 1.7 g/dL protein, 0.2 mg/dL iron) and 140 mL/kg/day (78 kcal/dL, 2.2 g/dL protein, 0.4 mg/dL iron), respectively. Parenteral nutrition was discontinued at 120 mL/kg/day, enteral volumes increased 10-25 mL/kg/day, full feeds were considered 160 mL/kg/day, and energy increases were implemented if weight gain was <15 g/kg/day using Prolact+8 (95 kcal/dL) or Neosure (88 kcal/dL, Abbott Nutrition, Columbus, USA) in HMBF and BMBF groups, respectively. Both groups received multivitamin drops containing 375IU vitamin A, 200IU vitamin D and 17.5 mg vitamin C daily. Vitamin D 200IU was given daily until 2 kg. Each infant received 2-3 mg/kg/day elemental iron after full fortification. These doses were chosen bearing in mind the different micronutrient composition of the two diets while providing the same supplementation to both groups and thus maintaining blinding. The intervention lasted until 84 days of age, hospital discharge or establishment of oral feeds. The initial trial found no group differences in feeding tolerance or growth [3].