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.