Supplementary Material for: Preterm formula, fortified or unfortified human milk for very preterm infants, the PREMFOOD study, a parallel randomised feasibility trial

Objective: Uncertainty exists regarding optimal supplemental diet for very preterm infants if mother’s own milk (MM) is insufficient. We evaluated feasibility for a randomised controlled trial powered to detect important differences in health outcomes.
Methods: In this open, parallel, feasibility trial, we randomised infants 25+0-31+6 weeks gestation by opt-out consent, to one of three supplements to MM: unfortified human milk (UHM) (unfortified MM +/- unfortified pasteurised human donor milk (DM); fortified human milk (FHM) (fortified MM +/- fortified DM), and unfortified MM +/- preterm formula (PTF) from birth to 35+0 weeks post menstrual age. Feasibility outcomes included opt-outs, adherence rates, and slow growth safety criteria. We also obtained anthropometry, and magnetic resonance imaging body composition data at term and term plus 6 weeks (opt-in consent), as potential biomarkers for metabolic risk.
Results: 35 infants were randomised to UHM, 34 to FHM, and 34 to PTF groups, of which 21, 19, and 24 infants completed imaging at term. Opt-out consent was above target at 62%, while 6% of parents withdrew from feeding intervention. Two infants met predefined slow weight gain thresholds. There were no significant between-group differences in total adipose tissue volume at term (mean (sd): UHM: 0.870L (0.35L); FHM: 0.889L (0.31L); PTF: 0.809L (0.25L), p=0.66), nor in any other body composition measure or anthropometry at either timepoint.
Conclusions: Randomisation to UHM, FHM, and PTF feeding interventions by opt-out consent was acceptable to parents and clinical teams, associated with safe growth profiles, and body composition which did not indicate utility for biomarkers of metabolic risk.