Impact of Unfortified Human Milk, Fortified Human Milk, and Preterm Formula Intake on Body Composition at Term in Very Preterm Infants: Secondary Analysis of the PREMFOOD Trial

<b>Background/Objectives</b>: Very preterm body composition at term shows potential as a biomarker of later health outcomes, but effects from in-hospital formula versus human milk (HM) (maternal milk (MM) and/or pasteurised human donor milk (DM) supplement) intake studies are confounded by the effect from the fortifier. We investigated the impact of in-hospital unfortified HM (UHM), fortified HM (FHM), and preterm formula (PTF) intake on very preterm body composition at term. <b>Methods</b>: Preplanned analysis of the PREterM FOrmula or Donor milk (PREMFOOD) trial: Infants born at <32 weeks were randomised to either (i) UHM, (ii) FHM, or (iii) MM and/or PTF supplement. Main outcomes were assessed by anthropometry and magnetic resonance imaging of body composition at term. Secondary comparison between groups defined by proportion of milk intake from birth to 35 weeks postmenstrual age: The groups comprised exclusive UHM (ExUHM, proportion of UHM 99-100%, n = 23), predominantly UHM (PrUHM, UHM 50-98.9%, n = 15), predominantly FHM (PrFHM, FHM > 50%, n = 17), and predominantly PTF (PrPTF, PTF > 50%, n = 7). <b>Results</b>: At term, compared to the ExUHM group, the PrPTF group had 274.3 g (95% CI: 30.1 to 518.5) more Non-Adipose Tissue Mass (NATM) and a 1.11 times (95% CI: 0.38 to 1.84) greater increase in weight z score from birth, while both PrPTF and PrFHM had greater increases in length z scores from birth. <b>Conclusions</b>: High formula intake was associated with maximal gains in NATM at term, and these gains were not matched by the early fortification of HM. The alteration of body composition at term with prolonged or delayed HM fortification and its relation to later health outcomes are important research questions.