Preterm formula, human donor milk, and breast milk fortification for preterm infants
File(s)
Author(s)
Mills, Luke
Type
Thesis
Abstract
Evidence is lacking to inform on optimal very preterm diet and growth in relation to functional outcomes. Early adiposity is a potential biomarker of later metabolic disease, but its modification by early nutrition is unknown. The aims of the thesis were to (i) investigate relationships between early diet, macronutrient intake, growth, body composition, and insulin sensitivity, and (ii) evaluate the feasibility of a larger randomised controlled trial powered to detect differences in functional health outcomes. Infants <32 weeks gestation were randomised within 48 hours of birth to receive unfortified human milk (UHM) (unfortified mother’s own milk [MOM] +/- unfortified pasteurised donor milk [pHDM]) supplement), fortified human milk (FHM) (fortified MOM +/- fortified pHDM supplement), and unfortified MOM +/- preterm formula (PTF) supplement from birth to 35+0 weeks post-menstrual age (PMA). Primary outcome was total adipose tissue (TAT) volume at term, measured by whole body magnetic resonance imaging. Secondary outcomes were regional adipose tissue volumes and anthropometry at term and term plus 6 weeks, and quantitative insulin sensitivity check index at 35 weeks PMA. Thirty-five infants were randomised to UHM, 34 to FHM, and 34 to PTF groups, of which 21, 19, and 24 infants completed imaging at term, and 14, 5, and 19 respectively, at term plus 6 weeks. There were no significant between-group differences in TAT at term (mean (sd): UHM: 0.870L (0.35L); FHM: 0.889L (0.31L); PTF: 0.809L (0.25L), p=0.66) or in any other outcome. Agreement to participate in the feeding intervention using an opt-out process was 62%, and 55% consented to imaging using an opt-in approach. Two infants developed severe necrotising enterocolitis, and 2 met a predefined weight gain threshold to receive rescue fortifier/formula. Early macronutrient intake had no persistent effect on body composition, with an early preferential adipose tissue deposition changing to non-adipose tissue mass gains by 35 weeks PMA. Very preterm infants fed UHM, FHM, or PTF as supplements to MOM have comparable body composition and growth at term and term plus 6 weeks. Trial design and feeding interventions were safe, feasible, and acceptable to parents and clinical teams. Modification of body composition by prolonged, or later in-hospital use of fortifier, and relation to functional outcomes are important research questions.
Version
Open Access
Date Issued
2021-11
Date Awarded
2022-09
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
Advisor
Modi, Neena
Publisher Department
School of Public Health
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)