Protein requirements in preterm infants: effect of different levels of protein intake on growth and body composition. Growth, nutrient retention, and metabolic response in low birth weight infants fed varying intakes of protein and energy. Calciuria and aminoaciduria in very low birth weight infants fed a high-mineral premature formula with varying levels of protein. Clinical effects of two different levels of protein intake on low-birth-weight infants. A comparative study of varying protein intake in low birthweight infant feeding. Effect of varying protein intake on energy balance, protein balance and estimated weight gain composition in premature infants. Effect of protein/energy ratio on growth and behavior of premature infants: preliminary findings. Effects of varying protein and energy intakes on growth and metabolic response in low birth weight infants. Milk protein quantity and quality in low-birthweight infants: I. Metabolic responses and effects on growth.
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. Growth, nutrient retention, and metabolic response were determined in low birth weight (LBW) infants fed daily protein and energy intakes, respectively, of 2.8 gm/kg and 119 kcal/kg (group 1), 3.8 gm/kg and 120 kcal/kg (group 2), and 3.9 gm/kg and 142 kcal/kg (group 3). The mean rates of both weight gain and nitrogen retention in group 1 were somewhat greater than intrauterine rates; plasma concentrations of transthyretin and albumin also were acceptable. Thus the lower protein intake appeared to be adequate. On the other hand, the rates of weight gain and nitrogen retention in groups 2 and 3 were greater than those in group 1, supporting the efficacy of the higher protein intake with respect to growth. However, blood urea nitrogen and plasma amino acid concentrations also were higher in groups 2 and 3; both were higher in group 2 than in group 3, reflecting the positive effect of the higher energy intake on protein utilization. This observation, combined with data from an earlier study, indicates that protein intakes in excess of 3 gm/100 kcal will not be utilized completely. Energy expenditure in group 3 was greater than in group 1 but not group 2, raising the possibility that protein intakes not utilized completely contribute to diet-induced thermogenesis. The higher energy intake in group 3 vs group 2 did not affect rate of weight gain significantly, but energy storage in group 3, and hence fat accretion, was greater than that of other groups. In all groups the ratio of protein accretion to fat accretion reflected dietary proportions of protein and energy. To assess the influence of protein intake on renal excretion of calcium and amino acids and on bone mineralization in preterm infants, we randomly selected within weight group strata 27 infants who weighed < 1500 gm at birth (nine per group) to be fed a high-mineral (calcium, 940 mg/L; phosphorus, 470 mg/L) premature formula with one of the following protein contents: formula A, 3.0 gm/100 kcal; formula B, 2.7 gm/100 kcal; and formula C, 2.2 gm/100 kcal. Mean (+/- SD) daily weight gain was greater in infants receiving the higher protein intakes for the first 30 days (formula A, 24.8 +/- 5.1 gm; formula B, 20.5 +/- 3.8 gm; formula C, 16.2 +/- 5.9 gm (analysis of variance: p < 0.01; C < A, p < 0.05)). Bone mineral content did not differ at any time point, and all groups had a high prevalence of generalized aminoaciduria (4 weeks: formula A, 56%; formula B, 71%; formula C, 75%). Urinary calcium corrected for creatinine (in milligrams per milligram) increased as protein content decreased (2 weeks: formula A, 0.16 +/- 0.10; formula B, 0.20 +/- 013; formula C, 0.44 +/- 0.33 (C > A, C > B, p < 0.05); 4 weeks: formula A, 0.23 +/- 0.15; formula B,0.34 +/- 0.47; formula C, 0.49 +/- 0.22 (C > A, p < 0.01). We conclude that the high mineral content and other components of premature formulas result in a higher growth rate and may increase protein requirements. Failure to meet protein requirements may result in underutilization of absorbed calcium and increased renal excretion of calcium. In preterm infants, higher protein intake probably supports rather than jeopardizes bone mineral accretion, and reduces rather then increases calciuria. nan 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. We studied the effect of varying only protein intake on energy balance, protein balance and estimated weight gain composition in premature infants fed either a formula with a protein content of 2.0 g/100 ml (F2) or a protein content of 1.5 g/100 ml (F1.5).
                Premature infants were randomly allocated to receive F1.5 or F2. Weight gain composition was estimated from protein and energy balances. Energy expenditure was measured with doubly labelled water.
                F1.5, n = 8; gestational age 32 +/- 3 weeks, birth weight 1716 +/- 560 g. F2, n = 8; gestational age 32 +/- 3 weeks, birth weight 1544 +/- 488 g.
                Infants fed F2 showed a significantly higher protein accretion (P = 0.003) and weight gain (P = 0.011) when compared to the infants fed F1.5. There were no differences in the energy balance. The estimated weight gain composition was different between both groups.
                The F2 fed infants had an estimated weight gain composition comparable to the reported intrauterine values, while the F1.5 fed infants showed a weight gain composition more comparable to the reported values of the full term infant. The impact of nutrient composition in premature infant formulas on body composition and growth is discussed. Premature infants weighing less than 1550 gm at birth were randomly assigned to receive one of three formulas identical in composition except for protein content (2.2, 2.7, and 3.2 gm.100 kcal-1) to determine the effects on growth, protein nutritional status, and behavior. Data collected for 2 weeks from the time of achieving an enteral energy intake of 100 kcal.kg-1.day-1 included measurements of weight, length, head circumference, and skin-fold thickness, and concentrations of plasma amino acids, serum total protein, prealbumin, retinol-binding protein, and urea nitrogen. In a subset of infants, behavior was assessed at the end of the feeding study with the Neonatal Behavior Assessment Scale. Except for the concentrations of plasma amino acids, there were no significant differences in growth or in other biochemical measurements among the three groups, but there were significant differences in the orientation, habituation, and stability clusters of the behavior assessment. Further, there were significant correlations between the plasma amino acid values and the behavioral clusters. These preliminary data suggest a relationship between protein intake in the neonatal period and behavioral outcome at the end of the feeding period in the absence of differences in growth and gross markers of protein nutritional status. The behavioral items noted to differ among the groups may indicate later cognitive outcome; detailed studies about behavioral responses to neonatal dietary intakes and later outcome seem indicated. Growth (weight, length, head circumference, and skinfold thickness), retention of major nutrients (nitrogen, sodium, potassium, chloride, calcium, and phosphorus), and chemical indices of protein adequacy (plasma albumin and transthyretin concentrations) and excess (blood urea nitrogen concentration and acid-base status; plasma amino acid concentrations) were determined serially from the time desired intake was tolerated until discharge weight (2200 gm) was reached in low birth weight infants (birth weight 900 to 1750 gm) fed one of three formulas, which provided protein and energy intakes, respectively, of 2.24 gm/kg/day and 115 kcal/kg/day (group 1), 3.6 gm/kg/day and 115 kcal/kg/day (group 2), and 3.5 gm/kg/day and 149 kcal/kg/day (group 3). Weight gain and rate of increase in length and head circumference were less in group 1 than in groups 2 and 3. Retention of most major nutrients also was less in group 1, as was blood urea nitrogen concentration, plasma albumin and transthyretin concentrations, and plasma concentrations of several amino acids. The rate of weight gain was not significantly greater in group 3 than in group 2, but the rate of increase in skinfold thickness was greater in this group. Neither nutrient retention nor metabolic indices differed between groups 2 and 3. These results suggest that a protein intake of 2.24 gm/kg/day is inadequate for the type of LBW infants studied, that the higher protein intakes are well tolerated, and that an energy intake of 149 vs 115 kcal/kg/day does not enhance utilization of the higher protein intakes studied. The optimal quantity and quality of protein for low-birthweight infants is undefined. In this study, 106 well, appropriate-for-gestational age, low-birthweight infants weighing 2,100 gm or less were grouped in three gestational age categories: T1 = 28 to 30 weeks; T2 = 31 to 33 weeks; T3 = 34 to 36 weeks. Each group was assigned randomly to either banked human milk (BM) or to one of four isocaloric formulas varying in quantity and quality of protein but not in mineral content or in fat content: formula 1 = 1.5 gm of protein per 100 ml, 60 parts bovine whey proteins to 40 parts bovine caseins; formula 2 = 3.0 gm of protein per 100 ml, 60:40; formula 3 = 1.5 gm of protein per 100 ml, 18:82; formula 4 = 3.0 gm of protein per 100 ml, 18:82. Caloric intake was 117 kcal/150 ml/kg/day for the formulas. Human milk was fed at 170 ml/kg/day in order to attain a caloric intake approximately equal to that of the formulas. No significant differences were found in the rate of growth in crown-rump length, in femoral length, in head circumference, or in rate of gain in weight from time of regaining birthweight to time of discharge at 2,400 gm. Blood urea nitrogen, urine osmolarity, total serum protein, serum albumin, and serum globulin varied directly with the quantity of protein in the diet: F2, F4 greater than F1, F3 greater than BM. Blood ammonia concentration varied with both quantity and quality of protein in the diet: F2, F3, F4 greater than F1, BM. Metabolic acidosis was more frequent, more severe, and more prolonged in the infants fed the casein-predominant formulas (F3,F4) than in those fed the whey protein-predominant formulas (F1, F2).
Higher protein intake (≥ 3.0 g/kg/day but < 4.0 g/kg/day) from formula accelerates weight gain. However, there is limited information regarding the impact of higher formula protein intake on long-term outcomes such as neurodevelopmental abnormalities. The available evidence is not adequate to make specific recommendations regarding the provision of very high protein intake (> 4.0 g/kg/day) from formula in the initial hospital stay or after discharge.