Effect of Increased Enteral Protein Intake on Growth in Human Milk–Fed Preterm Infants

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 Infants were randomly assigned to either a lower-protein (adding 1 g of bovine protein/100 mL of 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/100 mL of breast milk [n = 15]) or individualized high-protein supplementation based on protein and fat content of administered breast milk (n = 15). Study interventions were continued for a median (IQR) of 41 (30-57) days and until definite discharge planning. MAIN OUTCOMES AND MEASURES Primary outcome was weight gain (g/kg/d) from birth to the end of intervention. RESULTS Sixty preterm infants (gestation <32 weeks and weight <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 birth was 29.9 (28.7-31.2) weeks. Demographic characteristics and hospital courses were similar in both groups, and birth weights ranged from 580 to 1495 g in the lower-protein group and 490 to 1470 g in the higher-protein group. Weight gain was 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 16.0 g/kg/d (15.1-16.9 g/kg/d) in the higher-protein group) (P = .70), despite an increase in actual protein intake by 0.6 g/kg/d (0.4-0.7 g/kg/d) (P < .001). Head circumference and lower leg longitudinal growth were also similar, as was the proportion of cumulative total enteral feeding volume provided as breast milk: median (IQR) proportion of breast milk, 92% (79%-98%) in the lower-protein group vs 94% (62%-99%) in the higher-protein group (P = .89). CONCLUSIONS AND RELEVANCE An increase in protein intake by 0.6 g/kg/d to a mean intake of 4.3 g/kg/d did not further enhance growth of very preterm infants with a median birth weight of 1200 g, who achieved near-fetal growth rates. This might point to a ceiling effect for enteral protein intake with respect to its influence on gr...

Modifications of Own Mothers’ Milk Fortification Protocol Affect Early Plasma IGF-I and Ghrelin Levels in Preterm Infants. A Randomized Clinical Trial

“…Regarding the effects of the fortification protocol on growth, we did not find any significant difference between the two groups up to the 12th month CA. Our findings are in agreement with previous studies in preterm infants fed fortified human milk with variable protein content [49][50][51]. However, a higher rate of weight gain in preterm infants receiving increased amounts of protein was reported by other authors [25,[52][53][54][55][56].…”

“…Specifically, in most studies, a proportion or all included infants were fed exclusively or partly banked donor milk [50][51][52][53][54][55], which contains lower protein than the preterm OMM [4,65], thereby requiring a higher fortification level. In other studies, a protein content of about 0.8-1.4 g/dL in human milk was assumed [49][50][51]54] or the protein intake was adjusted to blood urea levels [50,51,54,55].…”

Milk Curd Obstruction in Human Milk-Fed Preterm Infants

“…Results of several randomised controlled trials suggest that the gap cannot be overcome by increasing the amounts of amino acids provided by parenteral nutrition [28-30], whereas adding protein to human milk promotes the growth of extremely preterm infants [31-34]. However, there is an apparent ceiling at around 4 g/kg/day [35]. …”

Increased early enteral zinc intake improves weight gain in hospitalised preterm infants

“…A 2017 RCT of 60 preterm infants by Maas et al. showed that an increase in protein intake by 0.6 g/kg/day to a mean intake of 4.3 g/kg/day throughout the duration of NICU hospitalisation did not improve growth of preterm infants when compared to standard fortification guidelines. Similarly, a separate RCT of 60 preterm infants published in 2018 showed that fortification of human milk with an additional 0.7 g/kg/day of protein did not improve weight, length or head circumference growth during a 4‐week period .…”