A novel human milk fortifier supports adequate growth in very low birth weight infants: a non-inferiority randomised controlled trial

Abstract

Objective: To compare growth, tolerance and safety parameters in very preterm infants receiving human milk (HM) fortified with a multicomponent cow's milk-based HM fortifier (HMF; control) versus a novel HMF-containing lipids (including docosahexaenoic acid and arachidonic acid), higher protein and lower carbohydrate levels (test). Our hypothesis was that weight growth velocity in the test group would be non-inferior to that in the control group.

Design: Double-blind, randomised controlled trial.

Setting: Nine European neonatal intensive care units.

Patients: HM-fed infants born at <32-week gestational age.

Interventions: Fortification of HM with Test or Control HMF for a minimum of 21 days.

Primary outcome: Weight growth velocity between baseline and intervention day 21.

Results: From March 2018 to July 2020, 102 and 103 infants were enrolled in the test and control groups, respectively. Weight growth velocity during the first 21 days in the test group (mean 18.4 g/kg/day) was non-inferior to that of controls (mean 18.5 g/kg/day), with a difference in estimated means of -0.175 g/kg/day (90% CI -1.34 to +0.99 g/kg/day; per-protocol population). No significant differences between groups were observed for gain in length, head circumference or anthropometric Z-scores. Rates of digestive intolerance, stool frequency and consistency were comparable. No significant differences were reported in common neonatal morbidities including necrotising enterocolitis (test: 2.9%, control: 6.9%, mean difference -4.0% (95% CI -11.1% to 2.2%); all subjects treated population).

Conclusions: Use of the novel HMF containing lipids, higher protein and lower carbohydrate levels supports adequate postnatal growth and appears safe and well tolerated in very preterm infants.

Trial registration number: NCT03315221.

Keywords: Growth; Intensive Care Units, Neonatal; Neonatology.

Figure 1. Subject flow. HMF, human milk fortifier. ^‡Allocated subjects were siblings assigned to the same group. ^#One subject randomised to the Control group received Test HMF. ³Noncompliance with study: subjects with major protocol deviations: A. Major violation of the inclusion or exclusion criteria: n=0. B. Non-compliance with study product intake, as indicated by exposure to study product for <21 days: n=50. C. Not having any post-baseline measurements of weight – no additional exclusions. ⁴PP subjects were all subjects without major protocol deviations.