Effect of increased enteral protein intake on growth in human milk-fed preterm infants a randomized clinical trial

Abstract

IMPORTANCE Protein, supplied in currently available commercial fortifiers, may be inadequate to meet the requirements of very preterm infants; in addition, intraindividual and interindividual variability of human milk protein and energy content potentially contribute to unsatisfactory early postnatal growth. OBJECTIVE To determine effects on growth of different levels of enteral protein supplementation in predominantly human milk-fed preterm infants. DESIGN, SETTING, AND PARTICIPANTS This randomized clinical and partially blinded single-center trial was conducted in a neonatal tertiary referral center in Germany. Sixty preterm infants (gestation <32 weeks and weight <1500 g at birth) were recruited from October 2012 to October 2014 and included 35%of 173 eligible infants. Median (interquartile range [IQR]) gestational age at birth was 29.9 (28.7-31.2) weeks. All analyses were conducted in an intention-to-treat population. INTERVENTIONS Infantswere randomly assigned to either a lower-protein (adding1gof bovine protein/100mLof breast milk through a commercial human milk fortifier; n = 30) or a higherprotein group at a median (IQR) postnatal age of 7 (6-8) days. The higher-protein group (n = 30) received either standardized higher-protein supplementation (study fortifier adding 1.8 g of bovine protein/100mLof breast milk [n = 15]) or individualized high-protein supplementation based on protein and fat content of administered breast milk (n = 15). Study interventionswere continued for a median (IQR) of 41 (30-57) days and until definite discharge planning. MAIN OUTCOMES AND MEASURES Primary outcomewasweight gain (g/kg/d) from birth to the end of intervention. RESULTS Sixty preterm infants (gestation <32weeks andweight <1500 g at birth), 33 girls,were recruited from October 2012 to October 2014 and included 35%of 173 eligible infants. Median (IQR) gestational age at birthwas 29.9 (28.7-31.2)weeks. Demographic characteristics and hospital courseswere similar in both groups, and birthweights ranged from 580 to 1495 g in the lower-protein group and 490to 1470g in the higher-protein group.Weight gainwas similar in the lower- and higher-protein groups: mean (95%CI), 16.3 g/kg/d (15.4-17.1 g/kg/d) in the lowerprotein group vs 16.0g/kg/d (15.1-16.9 g/kg/d) in the higher-protein group) (P = .70), despite an increase in actual protein intake by0.6 g/kg/d (0.4-0.7 g/kg/d) (P