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.

研究目标：当母亲自身母乳（mother’s own milk，MM）不足时，极早产婴儿的最优补充喂养方案仍存在不确定性。本研究评估了一项随机对照试验的可行性，该试验具备足够检验效能以检测健康结局中的重要差异。
研究方法：本研究为开放标签、平行对照可行性试验。我们采用选择退出式知情同意，将胎龄25+0~31+6周的婴儿随机分配至3种母亲自身母乳补充方案之一，干预周期为出生至矫正胎龄35+0周：① 未强化母乳（unfortified human milk，UHM）组：未强化的母亲自身母乳±未强化巴氏消毒捐赠母乳（pasteurised human donor milk，DM）；② 强化母乳（fortified human milk，FHM）组：强化的母亲自身母乳±强化捐赠母乳；③ 早产配方奶补充组（unfortified milk + preterm formula，PTF）：未强化的母亲自身母乳±早产配方奶（preterm formula，PTF）。可行性结局指标包括选择退出率、干预依从率及生长迟缓安全性标准。本研究还采集了足月时及足月后6周（需签署选择加入式知情同意）的人体测量学数据与磁共振成像（magnetic resonance imaging，MRI）身体成分数据，作为代谢风险的潜在生物标志物。
研究结果：本研究共纳入35例随机分配至UHM组、34例至FHM组、34例至PTF组的婴儿，其中分别有21例、19例、24例完成了足月时的影像学检查。选择退出率为62%，高于预设目标；另有6%的家长退出了喂养干预。2例婴儿达到预设的体重增长迟缓阈值。三组在足月时的总脂肪组织容积（均值(标准差)：UHM组：0.870L(0.35L)；FHM组：0.889L(0.31L)；PTF组：0.809L(0.25L)，p=0.66）及其他身体成分指标、任意时间点的人体测量学指标上均无显著组间差异。
研究结论：通过选择退出式知情同意将婴儿随机分配至UHM、FHM及PTF喂养干预方案，获得了家长与临床团队的认可，且喂养相关生长状况安全；三组的身体成分未显示出可作为代谢风险生物标志物的应用价值。