Body composition of extremely preterm infants fed protein-enriched, fortified milk: a randomized trial

Abstract

Background: Critically ill extremely preterm infants fed human milk are often underrepresented in neonatal nutrition trials aimed to determine the effects of enteral protein supplementation on body composition outcomes.

Methods: Masked randomized trial in which 56 extremely preterm infants 25-28 weeks of gestation were randomized to receive either fortified milk enriched with a fixed amount of extensively hydrolyzed protein (high protein group) or fortified milk without additional protein (standard protein group).

Results: Baseline characteristics were similar between groups. In a longitudinal analysis, the mean percent body fat (%BF) at 30-32 weeks of postmenstrual age (PMA), 36 weeks PMA, and 3 months of corrected age (CA) did not differ between groups (17 ± 3 vs. 15 ± 4; p = 0.09). The high protein group had higher weight (-0.1 ± 1.2 vs. -0.8 ± 1.3; p = 0.03) and length (-0.8 ± 1.3 vs. -1.5 ± 1.3; p = 0.02) z scores from birth to 3 months CA. The high protein group also had higher fat-free mass (FFM) z scores at 36 weeks PMA (-0.9 ± 1.1 vs. -1.5 ± 1.1; p = 0.04).

Conclusions: Increased enteral intake of protein increased FFM accretion, weight, and length in extremely preterm infants receiving protein-enriched, fortified human milk.

Impact: Extremely preterm infants are at high risk of developing postnatal growth failure, particularly when they have low fat-free mass gains. Protein supplementation increases fat-free mass accretion in infants, but several neonatal nutrition trials aimed to determine the effects of enteral protein supplementation on body composition outcomes have systematically excluded critically ill extremely preterm infants fed human milk exclusively. In extremely preterm infants fed fortified human milk, higher enteral protein intake increases fat-free mass accretion and promotes growth without causing excessive body fat accretion.

Conflict of interest statement

P.C.-L. and A.A.S. have filed a patent application for an instrumented feeding bottle. A.A.S. has received honoraria from the Lockwood Group for participation in Mead Johnson Nutrition advisory board meetings. W.A.C. is on the board of directors of Mednax, Inc. M.J., A.F., and J.R. have no financial conflicts to disclose. The protein supplement used in this study was provided free of charge by Abbott. Abbott had no role in the design of the study, collection, analysis, interpretation of data, or writing of the manuscript.

© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.

Figures

Fig. 1. Participant flow diagram.

Enrollment, randomization, and outcomes.

Fig. 2. Energy and protein intake according to intervention group.

Longituinal changes in energy intake (a), protein intake (b), and protein/energy ratios (c). Mean values and 95% CIs were adjusted with repeated measures analyses that assumed an unstructured variance and accounted for subject-to-subject variability (random effects) and a fixed interaction term between the study groups and time (fixed effects).

Fig. 3. Growth and body composition outcomes from birth to 3 months of corrected age according to intervention group.

Longituinal changes in body fat percentage (a), fat mass (b), fat-free mass (c), weight (d), length (e), and head circumference (f). Mean values and 95% CIs were adjusted with repeated measures analyses that assumed an unstructured variance and accounted for subject-to-subject variability (random effects) and a fixed interaction term between the study groups and time (fixed effects).