{
  "abstract": "Introduction To meet the elevated nutritional requirements of very low birthweight (<1500 g, VLBW) infants during hospitalisation, many neonatal units routinely add a fixed dose of multinutrient fortifier to human milk. Individualised approaches that either tailor macronutrient additions to routine analysis of milk composition (target fortification) or an infant’s metabolic response to nutrition (blood urea nitrogen (BUN) adjustable fortification) show short-term improvement in growth, but important outcomes such as longer-term neurodevelopment and major in-hospital morbidity have not been systematically assessed. The aim of our study is to determine whether target or BUN adjustable fortification of human milk, compared with standard fortification, during hospitalisation improves cognitive (primary), language and motor development of VLBW infants at 18–24 months corrected age (CA). Secondary outcomes include growth, body composition, mortality and serious morbidity.Methods and analysis This is a three-arm, pragmatic, multicentre, double-blind, randomised clinical trial of 615 human milk–fed infants born either (1) ≤1250 g or (2) <30 weeks and <1500 g. Once enteral feeds reach 100 mL/kg/day, and until 36 weeks corrected gestational age (CGA), infants are fed according to one of three fortification protocols: (1) standard fortification, in which a fixed dose of nutrients is added to human milk; (2) target fortification, in which values from twice weekly direct analysis of mother’s milk and each batch of donor milk are used to provide 4 and 4.8 g/kg/day true protein and fat, respectively; and (3) BUN adjustable fortification, in which weekly BUN values are used to adjust protein fortification of milk. Neurodevelopment is assessed using the Bayley-IV scale at 18–24 months CA. Growth, morbidities and nutrient intakes are recorded daily during hospitalisation, and skinfolds are measured at 36 weeks CGA and at 4 months CA. At 4 months CA, body composition is determined by air displacement plethysmography on a subset of infants.Ethics and dissemination Ethical approval was obtained from Clinical Trials Ontario (CTO) and local research ethics boards that are not CTO members. Study findings will be disseminated to clinicians at seminars and conferences and in peer-reviewed publications.Trial registration number NCT05308134.",
  "authors": [
    {
      "affiliations": [
        "Translational Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada",
        "Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada"
      ],
      "name": "Megan R Beggs"
    },
    {
      "affiliations": [
        "Translational Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada"
      ],
      "name": "Dubraiicka Pichardo"
    },
    {
      "affiliations": [
        "Translational Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada",
        "Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada"
      ],
      "name": "Annette Chrzaniecki"
    },
    {
      "affiliations": [
        "Allied Health Disciplines, Sinai Health, Toronto, Ontario, Canada"
      ],
      "name": "Kirsten Kotsopoulos"
    },
    {
      "affiliations": [
        "DAN Women & Babies Program, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada"
      ],
      "name": "Rosine Bishara"
    },
    {
      "affiliations": [
        "DAN Women & Babies Program, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada",
        "Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada"
      ],
      "name": "Eugene Ng"
    },
    {
      "affiliations": [
        "Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada",
        "Neonatal Intensive Care Unit, The Hospital for Sick Children, Toronto, Ontario, Canada"
      ],
      "name": "Christopher Tomlinson"
    },
    {
      "affiliations": [
        "Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada",
        "St. Michael’s Hospital, Unity Health Toronto, Toronto, Ontario, Canada"
      ],
      "name": "Douglas Campbell"
    },
    {
      "affiliations": [
        "Department of Pediatrics, William Osler Health System, Brampton, Ontario, Canada"
      ],
      "name": "Simone Vaz"
    },
    {
      "affiliations": [
        "Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada"
      ],
      "name": "Alex Kiss"
    },
    {
      "affiliations": [
        "Neonatology, IWK Health Centre, Halifax, Nova Scotia, Canada",
        "Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada",
        "Rogers Hixon Ontario Human Milk Bank, Sinai Health, Toronto, Ontario, Canada"
      ],
      "name": "Sharon Unger"
    },
    {
      "affiliations": [
        "Translational Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada",
        "Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada",
        "Department of Pediatrics, Sinai Health, Toronto, Ontario, Canada"
      ],
      "name": "Deborah L O’Connor"
    }
  ],
  "title": "MaxiMoM InForM: individualised fortification of human milk for very low birthweight infants— protocol of a three-arm randomised clinical trial",
  "uid": "12d9874d-b466-5376-9d08-18f55f0781cd"
}