BACKGROUND: In preterm infants, the timing of human milk fortification when maternal or donor milk is offered at volumes of 60-80 ml/kg/day within the first 36 hours after birth remains a matter of debate. OBJECTIVE: This trial assessed the impact of early human milk fortification (<
7 days postnatal age) on fat-free mass (FFM) z-scores. METHODS: This was an unmasked clinical trial involving preterm infants with birthweight <
1800 g and gestational ages ranging from 29 0/7 to 33 6/7 weeks gestation. Human milk-fed infants receiving feeding volumes of 60-80 ml/kg/day within the first 36 hours after birth were randomized to receive either early (between day 4 and 7) or delayed (between day 10 and 14) fortification using a bovine-derived fortifier. FFM was assessed at postnatal day 21 using air-displacement plethysmography. RESULTS: A total of 80 infants were randomized. The mean birthweight was 1488 g (SD: 233). Baseline characteristics did not differ between groups. Of 80 infants randomized shortly after birth, 74 had the primary outcome measured at approximately 35 weeks of postmenstrual age (IQR: 34 - 36). No statistically significant differences in FFM z-scores were observed between the two groups (-1.7 ± 0.9 compared with -1.8 ± 0.9
p=0.64), but the early fortification group had higher weight (median difference: +131 g
95% CI: 12, 236
p=0.03), higher FFM (median difference: +103 g
95% CI: 1, 193
p=0.03), and higher length (mean difference: +0.9 cm
95% CI: 0.1, 1.8
p=0.04) at the time of body composition assessment. CONCLUSION: In very preterm infants receiving early full enteral nutrition, providing early human milk fortification does not result in higher than usual FFM z-scores. This feeding strategy may, however, lead to a sustained increase in length, and transient increases in weight and FFM in grams. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT05525585
https://clinicaltrials.gov/study/NCT05525585.