Effect of Targeted vs. Standard Fortification of Breast Milk on Growth and Development of Preterm Infants (≤32 Weeks): Results from an Interrupted Randomized Controlled Trial.

Nutrients. 2023;15(3)
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Preterm birth results in a high risk of mortality and is a cause of several morbidities, including extrauterine growth restriction. Despite numerous proven benefits, the concentration of some nutrients in human milk may be too low to meet the high nutritional needs of premature infants. Thus, to ensure optimal growth and development, human milk fortification is recommended for all very low birth weight babies. The primary aim of this study was to determine whether tailored compared to the standard fortification of enteral nutrition improved weight gain velocity in preterm infants born at ≤32 weeks of gestation. This study is a randomised observer- and patient-blinded controlled multicentre superiority trial, with two parallel groups with a 1:1 allocation ratio. Due to shortage of staff, two out of three centres failed to randomise patients. Patients were assigned to standard or tailored enteral nutrition fortification groups. Results show that there is no statistically significant difference in the velocity of weight gain during the supplementation period in infants born before 32 weeks of gestation who received targeted fortification compared to those who received standard fortification. Changes in length and head circumference did not differ between the groups. Authors conclude that targeted milk modification is a strategy that may allow for the optimisation of growth in premature infants; however, feasibility and poor tolerance of feeds may be important obstacles in introducing this strategy to neonatal intensive care unit clinical practice.

Abstract

Human milk is recommended for very low birth weight infants. Their nutritional needs are high, and the fortification of human milk is a standard procedure to optimize growth. Targeted fortification accounts for the variability in human milk composition. It has been a promising alternative to standard fixed-dose fortification, potentially improving short-term growth. In this trial, preterm infants (≤32 weeks of gestation) were randomized to receive human milk after standard fortification (HMF, Nutricia) or tailored fortification with modular components of proteins (Bebilon Bialko, Nutricia), carbohydrates (Polycal, Nutricia), and lipids (Calogen, Nutricia). The intervention started when preterms reached 80 mL/kg/day enteral feeds. Of the target number of 220 newborns, 39 were randomized. The trial was interrupted due to serious intolerance in five cases. There was no significant difference in velocity of weight gain during the supplementation period (primary outcome) in the tailored vs. standard fortification group: 27.01 ± 10.19 g/d vs. 25.84 ± 13.45 g/d, p = 0.0776. Length and head circumference were not significantly different between the groups. We found the feasibility of targeted fortification to be limited in neonatal intensive care unit practice. The trial was registered at clinicaltrials.gov NCT:03775785.

Lifestyle medicine

Fundamental Clinical Imbalances : Structural
Patient Centred Factors : Mediators/Preterm infant
Environmental Inputs : Diet ; Nutrients
Personal Lifestyle Factors : Nutrition
Functional Laboratory Testing : Not applicable

Methodological quality

Jadad score : 3
Allocation concealment : Yes

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