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. 2019 Nov 7;2019(11):CD013145. doi: 10.1002/14651858.CD013145.pub2

O'Connor 2018.

Methods Randomized clinical trial
Participants 127 infants < 1250 g
Exclusion criteria: Receipt of formula or bovine milk‐based fortifier prior to randomization and if enteral feeding not commenced within 14 days after birth. Congenital or chromosomal anomaly affecting growth. Setting: 2 tertiary NICUs, Sinai Health System and The Hospital for Sick Children, Toronto, Canada.
Interventions Intervention: (N = 64) Mother's own milk or pasteurized donor human milk fortified with human milk‐based fortifier (HMBF) (Prolact+, Prolacta Bioscience) to achieve 0.81 kcal/mL (24 kcal/oz), and 0.88 kcal/mL (26 kcal/oz), Control: (N = 63) Mother's own milk or pasteurized donor human milk fortified with bovine milk‐based fortifier (BMBF) (Similac Human Milk Fortifier Powder, Abbott Nutrition) to 0.72 kcal/mL (22 kcal/oz) and 0.78 kcal/mL (24 kcal/oz), and with the addition of powdered formula (Similac Neosure, Abbott Nutrition) to further concentrate feeds to 0.88 kcal/mL (26 kcal/oz).
Outcomes
  • Interruption in enteral feeding unrelated to clinical procedure ≥ 12 hours or a > 50% reduction in feed volume

  • Days of parenteral nutrition

  • Growth

  • Dichotomous mortality and morbidity index including NEC Stage ≥ 2, chronic lung disease, severe retinopathy of prematurity, and late‐onset sepsis

  • Fecal calprotectin

Notes Fortification of breast milk in both groups commenced at feed volumes of ≥ 100 mL/kg/d. In the HMBF group, fortification began at 0.81 kcal/mL (24 kcal/oz), and increased to 0.88 kcal/mL (26 kcal/oz) when volume reached 140 mL/kg/d. In the BMBF group, fortification began at 0.72 kcal/mL (22 kcal/oz) and increased to 0.78 kcal/mL (24 kcal/oz) when volumes reached 140 mL/kg/d. In the BMBF group, intact‐protein modular (Beneprotein, Nestle) was added to donor milk after fortification had reached up to 0.78 kcal/mL)
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk Block randomization of 4
Allocation concealment (selection bias) Low risk Allocation by an online third party service
Blinding of participants and personnel (performance bias) 
 All outcomes Low risk Triple‐blind study. Feeding assignments were masked using amber colored tubing and color wrapping for bottles.
Blinding of outcome assessment (detection bias) 
 Self‐reported outcomes Low risk Triple‐blind study. The reporting team was blinded to the intervention.
Blinding of outcome assessment (detection bias) 
 Objective outcomes Low risk Triple blind‐study. The reporting team was blinded to the intervention.
Incomplete outcome data (attrition bias) 
 All outcomes Low risk Two infants (2/63) in the control group were excluded since they died before intervention.
Selective reporting (reporting bias) Low risk All outcomes planned were reported.
Other bias Low risk None noted

BMBF: Bovine milk‐derived fortifier
 HMBF: Human milk‐derived fortifier
 NEC: Necrotizing enterocolitis
 NICU: Neonatal intensive care unit