Effect of targeted vs standard fortification of breast milk on growth and development of preterm infants (≤32weeks): study protocol for a randomized controlled trial

BackgroundHuman milk is recommended for all very low birth weight infants. Breastmilk is highly variable in nutrient content, failing to meet the nutritional demands of this group. Fortification of human milk is recommended to prevent extrauterine growth retardation and associated poor neurodevelopmental outcome. However, standard fortification with fixed dose multicomponent fortifier does not account for the variability in milk composition. Targeted fortification is a promising alternative and needs further investigation.MethodsThis randomized controlled trial will recruit preterm infants (<= 32weeks of gestation) within the first 7days of life. After reaching 80ml/kg/day of enteral feeding, patients will be randomized to receive standard fortification (HMF, Nutricia) or targeted fortification (modular components: Bebilon Bialka, Nutricia-protein; Polycal, Nutricia-carbohydrates; Calogen, Nutricia-lipids). The intervention will continue until 37weeks of post-conception age or hospital discharge. Parents and outcome assessors will be blinded to the intervention. The primary outcome measure is velocity of weight, length, and head growth until 36weeks post-conceptional age or discharge. Secondary outcomes include neurodevelopment at 12months assessed with Bayley Scale of Development III, repeated at 36months; body composition at discharge and at 4months; and incidence of necrotizing enterocolitis, sepsis, retinopathy of prematurity, and bronchopulmonary dysplasia.DiscussionTargeted fortification has previously been shown as doable in the neonatal intensive care unit context. If it shows to improve growth and neonatal outcome, choosing the targeted fortification as a first line nutritional approach in very low birth weight infants may become a recommendation.Trial registrationClinicalTrials.govNCT03775785, Registered on July 2019.