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Randomized Controlled Trial
. 2024;121(2):222-232.
doi: 10.1159/000535498. Epub 2023 Dec 13.

Preterm Formula, Fortified or Unfortified Human Milk for Very Preterm Infants, the PREMFOOD Study: A Parallel Randomised Feasibility Trial

Luke Mills  1   2 , Karyn E Chappell  2 , Robby Emsley  1   2 , Afshin Alavi  3 , Izabela Andrzejewska  1   2 , Shalini Santhakumaran  2 , Richard Nicholl  4 , John Chang  5 , Sabita Uthaya  1   2 , Neena Modi  1   2
Affiliations
Randomized Controlled Trial

Preterm Formula, Fortified or Unfortified Human Milk for Very Preterm Infants, the PREMFOOD Study: A Parallel Randomised Feasibility Trial

Luke Mills et al. Neonatology. 2024.

Abstract

Objective: Uncertainty exists regarding optimal supplemental diet for very preterm infants if the mother's own milk (MM) is insufficient. We evaluated feasibility for a randomised controlled trial (RCT) powered to detect important differences in health outcomes.

Methods: In this open, parallel, feasibility trial, we randomised infants 25+0-31+6 weeks of gestation by opt-out consent to one of three diets: unfortified human milk (UHM) (unfortified MM and/or unfortified pasteurised human donor milk (DM) supplement), fortified human milk (FHM) (fortified MM and/or fortified DM supplement), and unfortified MM and/or preterm formula (PTF) supplement 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).

Results: Of 35 infants randomised to UHM, 34 to FHM, and 34 to PTF groups, 21, 19, and 24 infants completed imaging at term, respectively. Study entry opt-out rate was 38%; 6% of parents subsequently withdrew from feeding intervention. Two infants met predefined slow weight gain thresholds. There were no significant between-group differences in term total adipose tissue volume (mean [SD]: UHM: 0.870 L [0.35 L]; FHM: 0.889 L [0.31 L]; PTF: 0.809 L [0.25 L], p = 0.66), nor in any other body composition measure or anthropometry at either timepoint.

Conclusions: Randomisation to UHM, FHM, and PTF diets by opt-out consent was acceptable to parents and clinical teams, associated with safe growth profiles and no significant differences in body composition. Our data provide justification to proceed to a larger RCT.

Keywords: Clinical outcomes; Clinical trial; Nutrition.

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Conflict of interest statement

N.M. reports grants outside the submitted work from the Medical Research Council, National Institute for Health Research, Prolacta Life Sciences, Chiesi International, Bayer International, Westminster Children’s Research Trust, European Health Data and Evidence Network, HCA International, Health Data Research UK, Shire Pharmaceuticals, and March of Dimes; N.M. accepts no personal remuneration for her role as a member of the Nestle International Scientific Advisory Board. The other authors have no conflicts of interest to disclose.

Figures

Fig. 1.
Fig. 1.
Consort diagram for study infants; FI (Feed Intervention Birth to 34+6 weeks PMA).
Fig. 2.
Fig. 2.
Box plots for (a) weight, (b) length, and (c) occipital frontal circumference (OFC) Z score change from birth to 35 weeks post menstrual age, term, and term plus 6 weeks age for randomised feed groups. Solid line is median, box is interquartile range (IQR), whiskers are 1.5 × IQR; ●p < 0.05; *Outlier (>1.5 × IQR) ○ Outlier (>3 × IQR).
See this image and copyright information in PMC

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