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

Background: /Objectives: 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) intake studies are confounded by effect from 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. Methods: Pre-planned secondary analysis of the PREterM FOrmula Or Donor milk (PREMFOOD) trial. Infants born <32 weeks were randomized to either (i) unfortified mother’s own milk (MM) and/or unfortified pasteurised human donor milk (DM) (UHM) (ii) fortified MM and/or fortified DM (FHM), or (iii) unfortified MM and/or preterm formula (PTF) from birth to 35+0 weeks post menstrual age. Main outcomes were anthropometry and magnetic resonance imaging body composition at term. Comparison between exclusive UHM (ExUHM: UHM >99% n=23) and predominant (Pr) actual feed exposure groups: PrPTF (PTF>50% n=7); PrFHM (FHM >50% n=17), and PrUHM (UHM 50-99% n=15). Results: At term, compared to ExUHM group, PrPTF group had 274.3g (95% CI: 30.1 to 518.5) more Non-Adipose Tissue Mass (NATM) and a 1.11 (95% CI: 0.38 to 1.84) greater increase in wieght z-score from birth, while both PrPTF and PrFHM had greater increases in length z- scores from birth. Conclusions: High formula intake was associated with maximal gains in NATM at term, and these gains were not matched by early fortification of HM. Alteration of body composition at term with prolonged or delayed HM fortification, and relation to later health outcomes are important research questions.