Supplementation with human milk protein improves growth of small premature infants fed human milk. Randomized outcome trial of human milk fortification and developmental outcome in preterm infants. Improved bone mineralization and growth in premature infants fed fortified own mother's milk. Growth, biochemical status, and mineral metabolism in very-low-birth-weight infants receiving fortified preterm human milk. A comparative study of varying protein intake in low birthweight infant feeding. Growth, nutrient retention, and metabolic response of low-birth-weight infants fed supplemented and unsupplemented preterm human milk. Growth and nutrient intakes of human milk-fed preterm infants provided with extra energy and nutrients after hospital discharge. The metabolic consequences of human milk and formula feeding in premature infants. Protein requirements in preterm infants: effect of different levels of protein intake on growth and body composition.
We investigated the influence of human milk protein and medium-chain triglyceride supplementations of human milk feedings on the growth of very low birth weight infants during their first weeks of life. A group of 44 preterm infants with birth weights of less than 1,520 g and a mean gestational age of 30.3 weeks was randomly divided into four groups to receive plain human milk or human milk supplemented with human milk protein (0.9 g/dL), with medium-chain triglycerides (1 g/dL), or with both. The medium-chain triglyceride oil supplementation did not influence the growth of these infants. The infants given supplementary protein gained weight faster during weeks 4 to 6 than those without (18.5 +/- 0.7 v 15.1 +/- 0.6 g/kg/d; mean +/- SEM; P = .001). After 4 weeks of age the infants given supplementary protein had a mean weight gain equal to the mean intrauterine rate, in contrast to the infants of the other groups, who grew more slowly until age 6 weeks. Furthermore, we found a correlation between serum albumin concentration and weight gain during the seventh week of life (P = .018). The length growth velocity for the infants with protein supplementation was 0.99 +/- 0.06 cm/wk (mean +/- SEM) and for those without 0.83 +/- 0.05 cm/wk (P = .043). There was no difference in growth of head circumference between the groups. We conclude that human milk protein supplementation improves the growth of small premature infants fed human milk, and that the protein concentration of bank milk is insufficient for their adequate growth. Despite potential benefits, human milk may fail to meet preterm infants' nutrient requirements. We tested the hypothesis that fortified breast milk, fed alone or with preterm formula, would improve neurodevelopment and growth at 18-mo follow-up without adverse short-term clinical or biochemical consequences. Two hundred seventy-five preterm infants from two medical centers (birth weight < 1850 g; mean gestation 29.8 +/- 2.7 wk) whose mothers chose to provide breast milk were randomly assigned to receive for a mean of 39 d a multinutrient fortifier or control supplement containing phosphate and vitamins. Breast milk comprised 47.6% and 46.4% of enteral intake in fortified and control groups, respectively; preterm formula supplements were used when insufficient breast milk was available. Overall, there were no significant growth advantages with fortification; although, when breast milk exceeded 50% of intake, fortification promoted faster weight gain (an advantage of 1.6 g.kg-1.d-1; 95% CI: 0.1, 3.1; P < 0.05). Compared with control infants, the fortified group showed 1) higher plasma urea from week 2 (P = 0.04), 2) higher plasma calcium (mean 2.34 +/- 0.01 compared with 2.27 +/- 0.02 mmol/L; P = 0.003), 3) a greater rise in alkaline phosphatase by week 6 (P = 0.04), 4) more clinical infections (suspected plus proven; 43% compared with 31%, P = 0.04), 5) a nonsignificantly increased incidence of necrotizing enterocolitis (5.8% compared with 2.2%, P = 0.12), and 6) higher white cell and platelet counts. Developmental scores at 18 mo were slightly but not significantly higher in the fortified group. This study confirmed that breast milk fortifiers can improve short-term growth (when breast milk intakes are high); but beneficial effects on long-term development remained unproven. Future research is required to evaluate potential adverse consequences and explore more optimal fortification strategies. "Preterm" human milk fortified with protein (0.85 gm/dL), calcium (90 mg/dL), and phosphorus (45 mg/dL) was compared with unfortified preterm human milk as a feeding for low birth weight infants. Additionally, a special formula for low birth weight infants (Similac Special Care (SC), 20 cal/oz), was compared with a standard 20 cal/oz formula (Similac). Bone mineral content (BMC), as measured by photon absorptiometry, improved in the study groups fed fortified human milk and Similac SC formula during the first 6 weeks of full oral feedings. Even though the intakes of calcium in the groups fed fortified human milk and Similac SC formula approached the intrauterine requirement for Ca during the third trimester of pregnancy (150 mg/kg/d), the values for BMC in these two groups (37 to 39 mg/cm) at the completion of the study were still considerably less than the intrauterine values for radial BMC at 36 to 37 weeks gestational age (72.6 +/- 14.1 mg/cm). Furthermore, the relative phosphorus deficiency (as determined by increased urinary Ca excretion and increased renal tubular reabsorption of phosphate) in the human milk groups occurred with or without supplements of Ca and P. Rate of weight gain in the fortified human milk group was greater than that of the unfortified human milk group and was comparable to that of infants fed Similac SC formula. Rate of weight gain for the unfortified human milk group was similar to that of infants fed Similac formula containing 20 cal/oz. However, none of the four feeding groups exceeded the 50th percentile for weight at the time of discharge (36 to 37 weeks postconceptional age). The results suggest that fortifying preterm human milk with Ca, P, and protein for low birth weight infants will improve bone mineralization and rate of growth to levels comparable to those achieved with a special formula containing high amounts of protein, Ca, and P. We compared the growth, biochemical status, and mineral status of 30 very-low-birth-weight infants randomly assigned to receive preterm human milk (Group I, 10 infants) from their own mothers, fortified preterm human milk (Group II, 8 infants), or a high-caloric-density premature formula (Group III, 12 infants). Added to the infant's own mother's milk, a human milk fortifier at full strength provided additional protein (60:40 whey/casein, 0.7 g/dl), calories (4 kcal/oz), and minerals. Volume of intake, feeding tolerance, and complications were similar in the three groups. Infants receiving fortified preterm human milk showed growth, biochemical status, and mineral status similar to those receiving high-caloric-density formula, but infants receiving fortified preterm human milk grew faster (12.0 +/- 3.2 vs. 8.9 +/- 1.1 days/300 g, p less than 0.05), had higher serum protein (4.6 +/- 0.5 vs. 4.2 +/- 0.2 g/dl, p less than 0.05), and tended to have better mineral status (higher serum calcium, lower alkaline phosphatase, and higher serum phosphorus, none individually significant) than infants receiving preterm human milk alone. This study supports previous observations that fortified preterm human milk provides nutritional advantages for very-low-birth-weight infants. In a prospective longitudinal study of 48 very low birthweight and preterm infants with mean birthweight 1 385 +/- 343 and gestational age 30.8 +/- 2.9 w an assessment was made of the impact of varying the protein intake in the postnatal period from the 3rd to 7th week of life. The infants were randomly allocated to one of three dietary groups with isocaloric energy supply but different protein content--i.e. human milk (1.6 g/100 kcal), formula 1 (2.3 g/100 kcal) and formula 2 (3.0 g/100 kcal). In the human milk group 12 of 18 infants were fed their own mother's breastmilk. During the study period the mean weight gain was slightly higher in the infants fed formula 1 and 2. There were no group differences in S-albumin whereas B-urea-N and B-base deficit were significantly increased in the formula fed infants in comparison to infants fed human milk. After the study period until around 15 weeks of age the slope in weight gain remained slightly higher for formula fed infants. However, the gain in body length and head circumference was equal in all three groups. After around 8 months of age there was no difference in any growth parameter. Neurodevelopmental examinations showed no group differences during the follow-up period to 2 years of age. Growth, nutrient retention, and metabolic response of low-birth-weight infants fed human milk provided by their mother; this milk supplemented with bovine milk protein, calcium, phosphorus, and sodium; or pasteurized term human milk with the same supplement were monitored from the time desired intake was tolerated until weight reached 2200 g. The supplement resulted in greater rates of weight gain (20.5 +/- 2.3 vs 16.4 +/- 2.2 g.kg-1.d-1) and nitrogen retention (353 +/- 76 vs 270 +/- 53 mg.kg-1.d-1), increase in plasma transthyretin (TTR) concentration (7 +/- 16 vs -3 +/- 9 mg.L-1.wk-1), a higher mean plasma albumin concentration (34 +/- 3 vs 32 +/- 4 g/L), and a higher plasma TTR concentration at discharge (100 +/- 22 vs 75 +/- 24 mg/L). All these variables correlated significantly with total nitrogen intake, suggesting that the differences are attributable to the protein content of the supplement. The supplement also resulted in greater rates of calcium and phosphorus accretion but the plasma alkaline phosphatase activity of the supplemented vs the unsupplemented groups did not differ. The purpose of this pilot study was to determine whether mixing a multinutrient fortifier to approximately one half of the human milk fed each day for a finite period after discharge improves the nutrient intake and growth of predominantly human milk-fed low birth weight infants. We also assessed the impact of this intervention on the exclusivity of human milk feeding.
                Human milk-fed (> or = 80% feeding per day) low birth weight (750-1800 g) infants (n = 39) were randomly assigned at hospital discharge to either a control or an intervention group. Infants in the control group were discharged from the hospital on unfortified human milk. Nutrient enrichment of human milk in the intervention group was achieved by mixing approximately one half of the human milk provided each day with a powdered multinutrient human milk fortifier for 12 weeks after discharge. Milk with added nutrients was estimated to contain approximately 80 kcal (336 kJ) and 2.2 g protein/100 mL plus other nutrients. Intensive lactation support was provided to both groups.
                Infants in the intervention group were longer during the study period, and those born < or = 1250 g had larger head circumferences than infants in the control group. There was a trend toward infants in the intervention group to be heavier at the end of the intervention compared with those in the control group. Mean protein, zinc, calcium, phosphorus, and vitamins A and D intakes were higher in the intervention group.
                Results from this study suggest that adding a multinutrient fortifier to approximately one half of the milk provided to predominantly human milk-fed infants for 12 weeks after hospital discharge may be an effective strategy in addressing early discharge nutrient deficits and poor growth without unduly influencing human milk feeding when intensive lactation support is provided. Twenty premature low-birthweight infants were divided into two groups and assigned randomly to either a pooled human milk or to a cow's milk based infant formula feeding regimen. The protein intake was 2.0 g/kg/day in the human milk fed group and 4.4 g/kg/day in the formula fed group of infants. The concentrations of different metabolites were estimated at weekly intervals, and plasma amino acid analysis was performed biweekly on blood samples in the two groups of infants during the four-week study period. Formula milk fed infants had significantly lower fasting blood glucose levels and developed azotaemia, hyperaminoacidemia and metabolic acidosis in the early weeks of postnatal life. Blood lactate and plasma free fatty acid concentrations did not change significantly in the two groups during the study. No significant differences were found in the rate of weight gain between the two groups of infants, although formula fed infants regained their birthweight more slowly than human milk fed infants. High protein formula feeding causes potentially unfavorable metabolic and amino acid imbalances in preterm infants in the early postnatal life. This study compares growth and body composition in preterm infants (< or =1750 g birth weight, < or =34 wk gestation) fed three iso-caloric formulas (80 kcal/100 mL) with different protein concentrations (A = 3.3 g/100 kcal, B = 3.0 g/100 kcal, C = 2.7 g/100 kcal). The study began when full enteral feeding (150 mL/kg/d) was established and lasted until term plus 12 wk corrected age (T + 12 wca). Nutrient intake was closely monitored throughout the study; daily during initial hospital stay and following discharge averaged between each clinic visit. Anthropometry and serum biochemistries were determined weekly during initial stay and at each clinic visit. Body composition was measured after hospital discharge and at T + 12 wca. Seventy-seven infants were recruited. No differences were detected in birth/enrollment characteristics between the groups. Protein intake was closely paralleled by changes in serum urea nitrogen and differed between the groups. Infants in group A were heavier and longer and had greater head circumference at discharge, but this was confounded by a slightly older corrected age in this group. There were no significant anthropometric differences at term or T + 12 wca. No differences were detected in body composition between the groups following discharge or at T + 12 wca. An intake of 3.3 g/100 kcal appears safe and may promote increased growth before initial hospital discharge. After discharge, intakes greater than 2.7 g/100 kcal do not appear to offer clear advantage. Further studies are needed to more precisely define protein requirements in these nutritionally at-risk infants.
Protein supplementation of human milk in relatively well preterm infants results in increases in short term weight gain, linear and head growth. Urea levels are increased, which may reflect adequate rather than excessive dietary protein intake. Further research should be directed towards the evaluation of specific levels of protein intake in preterm infants and the clinical effects of supplementation with protein, including long term growth and neurodevelopmental outcomes. This may best be done in the context of refinement of available multicomponent fortifier preparations.