Early full enteral nutrition with fortified milk in very preterm infants: a randomized clinical trial

In preterm infants, the timing of human milk fortification when maternal or donor milk is offered at volumes of 60-80 mL/kg/d within the first 36 h after birth remains a matter of debate.

This trial assessed the impact of early human milk fortification (<7 d postnatal age) on fat-free mass (FFM) z-scores.

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 of gestation. Human milk-fed infants receiving feeding volumes of 60-80 mL/kg/d within the first 36 h after birth were randomly assigned to receive either early (between days 4 and 7) or delayed (between days 10 and 14) fortification using a bovine-derived fortifier. FFM was assessed at postnatal day 21 using air-displacement plethysmography.

A total of 80 infants were randomly assigned. The mean birthweight was 1488 g (SD: 233). Baseline characteristics did not differ between groups. Of 80 infants randomly assigned shortly after birth, 74 had the primary outcome measured at ∼35 wk of postmenstrual age (interquartile range: 34-36). No statistically significant differences in FFM z-scores were observed between the 2 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% confidence interval (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.

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. This study was registered at clinicaltrials.gov as NCT05525585.