Effects of formula protein level and ratio on infant growth, plasma amino acids and serum trace elements. II. Follow-up formula

Infants, that had been formula-fed from birth, were fed follow-up formula with 1.5, 2.2 or 2.9 g protein/dl together with 25 g of cereal/day as supplemental food, or formula only (15 g/dl). Formulas were started at 4 months of age and daily intake, anthropometric measurements and plasma samples taken at 5, 6 and 7 months. Protein intake was 2.0, 3.0 and 3.7 g/kg/d, respectively. Growth data were similar for all groups, as were hemoglobin and serum protein values. BUN values for the group fed only formula with 1.5 g protein/dl were lower than for the group fed the same formula with cereals and the other groups. Plasma amino acids were not affected by the addition of the small amount of cereals to the formula with 1.5 g protein/dl, but significantly higher levels of valine, leucine and histidine were found at 7 months for infants fed the two higher protein levels. The highest protein level also appeared to have a negative effect on plasma zinc levels. These results suggest that a protein level of 1.5 g/dl in follow-up formula (2.0 g/kg/d) is adequate during 4 to 7 months of age and that higher protein levels may be excessive.     

Free amino acids in full-term and pre-term human milk and infant formula

OBJECTIVE: Although the nutritional value of human milk has been thoroughly studied, few reports describing its free amino acid (FAA) content have been published. Although infant formulas are designed to approximate the nutrient composition of human milk, the content and concentration of free amino acids are unknown. We compared the FAA concentrations of milk from mothers of preterm and full-term infants with those in several infant formulas. METHOD: Human milk was obtained during three different stages of lactation (colostral, transitional and mature milk). Sixty-seven samples were collected from 44 healthy mothers of term infants and 23 mothers of premature infants 29 to 36 weeks gestation (mean 33 weeks). Two brands of powdered term formula (TF-A and TF-B) and two brands designed for preterm infants (PTF-A and PTF-B )were also studied. Ion exchange chromatography was used for free amino acid analysis. RESULTS: The mean concentration of total FAA in human milk was significantly higher than any of the infant formulas (8139 micromol/L for pre-term human milk; 3462 micromol/L for full term human milk; TF-A, 720 micromol/L; TF-B, 697 micromol/L; PTF-A, 820 micromol/L; PTF-B, 789 micromol/L) (P <0.01). FAA concentration in term and premature human colostral milk was significantly higher than in human transitional and mature milks (P <0.01). In comparing individual FAAs, there were significant differences in concentrations between term human milk and preterm milk except for phosphoethanolamine, hydroxyproline, asparagine, and alpha-amino-eta-butyric acid. There were significant differences in all FAA concentrations between all human milks and infant formulas (P <0.05), but no significant differences were found among the study formulas. CONCLUSION: The concentration of FAA is high in human colostral milk and decreases through the transitional and mature milk stages. FAA is higher in all human milks than in infant formulas.     

Feeding premature infants with human milk or preterm milk formula. Effects on postnatal growth and on circulating concentrations of intermediary metabolites, amino acids, and regulatory peptides

Results of a comprehensive longitudinal study comparing the effects of feeding healthy preterm infants with human milk or a specially adapted formula designed for the preterm infant are reported. 10 healthy infants were given human milk from birth, and 9 similar infants were given a formula which contained 80 kcal, 1.8 g protein, and 4.5 g fat per 100 ml. Anthropometric measurements were made weekly as were routine haematological and biochemical variables together with plasma amino acid and gastrointestinal regulatory peptide levels and metabolic fuel concentrations. Infants receiving the formula demonstrated a significantly greater growth velocity compared with infants receiving human milk. There were no significant differences between the two groups in routine haematological or biochemical variables measured nor in plasma insulin or blood glucose, lactate, pyruvate, or ketone body concentrations. Plasma amino acid profiles, however, did demonstrate some significant differences between the two groups with higher methionine and threonine levels in the formula-fed infants. Plasma motilin, enteroglucagon, neurotensin, cholecystokinin, gastric inhibiting polypeptide, and pancreatic polypeptide levels all demonstrated significant postnatal surges, with significant differences between the two groups in plasma gastric inhibiting polypeptide and pancreatic polypeptide concentrations.     

Randomized, double-blind comparison of growth in infants receiving goat milk formula versus cow milk infant formula

OBJECTIVE: To compare growth of infants fed goat milk infant formula (GMF) or cow milk infant formula (CMF) and to compare tolerability and safety of the two formulas. METHODS: The study was conducted in Auckland, New Zealand. This was a double-blind randomized controlled trial. Newborn term infants were randomized within 72 h of birth to GMF or CMF. Milk formula powder in single serve sachets were reconstituted and fed to infants from trial commencement until age 168 days. No other formula given from randomization until age 168 days. Infant weight, length and head circumference were measured at birth and age 14, 28, 56, 84, 112, 140 and 168 days. Bowel motion frequency and consistency, sleeping and crying patterns and adverse events were also measured. RESULTS: Seventy-two infants were randomized, 36 each to GMF or CMF, with 62 infants completing the intervention. At enrollment the average weight of infants in the GMF group (mean +/- SD) was 3.33 +/- 0.43 kg and in the CMF group 3.43 +/- 0.47 kg; and at study completion 8.07 +/- 0.90 kg (GMF) and 7.87 +/- 0.99 kg (CMF). The difference in average weight gain over the study period for the GMF group versus the CMF group was not significant (+309 g; 95% CI = -49 to +668, P = 0.09). Median daily bowel motion frequency was greater in the GMF group than the CMF group (2.4 vs 1.7, P = 0.01). There were no group differences in bowel motion consistency, duration of crying, ease of settling, or frequency of adverse events. CONCLUSION: Growth of infants fed GMF is not different to that of infants-fed CMF.     

Cow's milk allergy, incidence and pathogenetic role of early exposure to cow's milk formula

A study was performed in infants under the age of 12 months born during 1974 and admitted to St. G?ran's Children's Hospital with symptoms suggestive of cow's milk allergy (CMA). The aims of the study were to determine the role of early exposure to cow's milk formulas as a predisposing factor to CMA and to estimate the incidence of CMA in infancy. Twenty-five infants fulfilled the criteria for CMA. Available records were reviewed and a careful history was obtained from the mothers on two occasions. The patient group was compared with a control group. Sixteen of the 25 infants were exposed to cow's milk protein during their first week in the nursery for newborns, 6 were exposed before the end of the fourth week of life, and 3 infants were apparently not exposed. All infants were breast fed 3 to 26 weeks before re-exposure and occurrence of symptoms. Infants with CMA were given cow's milk formulas during their first 4 weeks of life significantly more often than infants in the control group (p less than 0.01). The incidence of CMA was approximately 1 : 200. The first 4 weeks after birth seem to be a particularly vulnerable period. Hence, in order to prevent CMA, infant formula should not be given--even occasionally--during this period.     

Plasma amino acids in small preterm infants fed on human milk or formula.

Plasma amino acids were measured in 35 preterm infants, of whom 11 weighed less than 1000 g and 24 weighed between 1000 g and 1500 g at the time of sampling. Repeat samples were obtained in 18 at least seven days later. Seventeen infants were fed with preterm formula milk and 18 with expressed maternal breast milk at one to two hourly intervals during the study period. Formula fed infants gained weight faster than those fed on breast milk but there was little difference in amino acid patterns. Infants fed on breast milk were more likely to have concentrations of essential amino acids below the mid trimester fetal range than formula fed infants, but few infants in either feeding group had values above the fetal range. Those that did were equally distributed between both groups. Only two samples approached toxic concentrations, both in the group fed breast milk. The ratio of branched chain to aromatic amino acids was higher in the group fed on formula after correction for post conceptional age, implying that liver maturation may be accelerated by formula feeding. No correlations were found between plasma amino acid concentrations and nitrogen retention or metabolisable energy intake.     

Milk protein intake in the term infant. II. Effects on plasma amino acid concentrations

The response of plasma amino acids to two bovine protein formulas with different protein content (1.6 and 1.2 g/100 ml containing 60% whey proteins and 40% caseins) was measured in term infants. These two groups of infants were compared with a group of infants that were breast-fed; all infants were fed ad libitum. Concentrations of threonine, valine and total branched chain amino acids reflected the amount of protein provided. Thus, the concentrations were higher in the higher protein formula infants from the second week of the study. In the low protein formula infants these amino acids were lower but differed from the infants on breast milk at eight and twelve weeks. Concentration of taurine was lower in the formula fed infants than they were in breast-fed infants at the end of the study. The valine/glycine ratio in the low protein formula group was lower than in the breast-fed group for the first four weeks of the study. After this time it was equal to that of the breast-fed group. These differences in plasma amino acid concentrations give further evidence that formulas now in common use for term infants provide a protein intake in excess of protein requirements after the first months of life.     

Effects of type of dietary protein on acid-base status, protein nutritional status, plasma levels of amino acids, and nutrient balance in the very low birth weight infant.

STUDY OBJECTIVE: To determine the effect of the type of dietary protein (3.3 gm/kg per day) on acid-base status, protein nutritional status, plasma amino acid concentrations, and nutrient (nitrogen, fat, mineral, trace element) balance. SUBJECTS: Preterm infants (birth weight less than or equal to 1250 gm, gestational age less than or equal to 32 weeks) with no evidence of systemic disease, who had achieved a minimal enteral intake of 110 kcal/kg per day by 21 days of age. INTERVENTIONS: Each infant was fed three study formulas that differed only with respect to the ratio of whey to casein (60:40, 35:65, 18:82). Each formula was given for 1 week. At the end each week, blood was drawn and a 48-hour balance was determined. MAIN RESULTS: Late metabolic acidosis, uremia, and hyperammonemia were not observed. No differences in pH or serum bicarbonate were noted. Base excess was greater with the casein-predominant formula (18:82 greater than 35:65, 60:40) but remained within normal limits for the preterm infant. Plasma concentrations of threonine (60:40 greater than 35:65 greater than 18:82), phenylalanine, and tyrosine (18:82 greater than 35:65 greater than 60:40) differed. Nitrogen absorption (60:40 less than 35:65, 18:82), nitrogen retention (60:40 less than 35:65, 18:82), fat absorption (60:40, 35:65 greater than 18:82), and phosphorus absorption (60:40 less than 35:65, 18:82) also differed. CONCLUSIONS: At an intake of 3.3 gm/kg per day, the type of dietary protein had little effect on metabolic status. Differences in plasma amino acid concentrations and nutrient balance suggest that a formula containing protein with a whey/casein ratio of 35:65 may be preferable to that with a whey/casein ratio of 60:40 or 18:82 for the very low birth weight infant.     

Growth, serum biochemistries, and amino acids of term infants fed formulas with amino acid and protein concentrations similar to human milk

We tested the hypothesis that amino acid intake from infant formulas modified to be similar to human milk would result in indices of protein metabolism more like those in human milk-fed infants. Formula-fed infants received for 12 weeks one of three isocaloric formulations of a whey-adapted formula that differed in protein concentration: 11, 13, or 15 g/L. Infants consumed similar volumes of formula or human milk. Serum urea nitrogen concentrations reflected the protein content of the diets. Plasma indices of protein nutritional status were normal and did not differ among groups. Growth rates of all infants were normal and similar. Serum indicators of protein nutritional status varied with age, which made comparisons of formula-fed infants with human milk-fed infants difficult. Plasma concentrations of leucine and isoleucine at 4 weeks of age were higher in infants fed the formula containing 15 g protein/L when compared with those of infants fed the other two formulas or human milk. At 8 and 12 weeks of age, all formula-fed infants had plasma amino acid profiles that did not differ significantly from each other except for isoleucine, which was lower in the 11-g/L group. We found that providing formulas with an amino acid pattern similar to that of human milk did not produce a plasma amino acid pattern identical to that of the breast-fed infant. This observation suggests that other factors, such as the hormonal response to feeding, differing nutritional bioavailability of amino acids from human and bovine milk proteins, and the changing quantity and type of amino acids with advancing lactation, influence plasma amino acid concentrations.     

Iron absorption from infant milk formula and the optimal level of iron supplementation

Thirty healthy infants, aged 11-13 months, were studied with regard to the iron absorption from proprietary milk formula. The infants were divided into three groups (I-III) depending on the concentration of iron in the formula: 0.8 (I), 6.8 (II), and 12.8 (III) mg/l, respectively. The calculated amount of iron absorbed per test dose of 50 ml of milk averaged 5 microgram (I), 32 microgram (II), and 43 microgram (III). Group I differed significantly from groups II and III. No correlation was found between iron absorption and hemoglobin, MCV, serum transferrin saturation or serum ferritin within the range of normal values. Our findings suggest that at least 7 mg of iron as ferrous sulphate per litre of formula is required to prevent iron deficiency.     

Protein hydrolysate formula maintains homeostasis of plasma amino acids in preterm infants.

BACKGROUND: Plasma amino acid concentrations were measured in preterm infants who were fed either a new hydrolyzed cow's milk protein formula or a standard preterm infant formula. It was hypothesized that feeding with the hydrolysate results in preprandial amino acid concentrations that are significantly different from the concentrations found when feeding with the standard formula. METHODS: Fifteen preterm infants, median gestational age, 29 weeks (range, 24-32 weeks); birth weight, 1241 g (range, 660-1900 g); and postnatal age, 18 days (range, 7-54 days) receiving full enteral feedings (>150 ml/kg x day), were enrolled. The intervention was randomized allocation to the formula with hydrolyzed or natural cow's milk protein (the whey/casein ratio was 60:40 in both formulas). In a crossover design, each formula was fed for 5 days, and plasma amino acids were analyzed on day 4 or 5 of each 5-day period. RESULTS: In spite of the 12% higher amino acid intake with hydrolysate formula, the median individual plasma amino acid concentrations were virtually identical with both formulas, and they were within the 10th and the 90th percentile of the reference of levels in the umbilical cord artery after elective cesarean delivery or of breast-fed newborn infants. The median concentrations of lysine and aspartic acid were higher with hydrolyzed formula feeding (p<0.05; two-tailed Mann-Whitney test). With both formulas, single amino acid concentrations were out of the reference values. CONCLUSION: Virtually identical plasma amino acid concentration patterns were measured with the new hydrolyzed preterm infant formula and the standard preterm infant formula, but longitudinal studies are required before the studied protein hydrolysate can be recommended for preterm feeding in general.     

Human milk protein and medium-chain triglyceride oil supplementation of human milk: plasma amino acids in very low-birth-weight infants

Fifty-one very low-birth-weight infants (birth weight less than 1,520 g) randomly fed either human milk or human milk supplemented with human milk protein and/or with medium-chain triglyceride (MCT) oil were observed. Plasma amino acids from these infants were studied at 2, 8, and 10 weeks. Medium-chain triglyceride oil supplementation had minimal or no influence on plasma amino acids. Human milk protein supplementation resulted in increased concentrations of all amino acids at all ages studied. The concentrations were 1.5- to threefold as compared with values in infants not given protein supplements. However, the concentrations of methionine, tyrosine, phenylalanine, and lysine remained far below values considered harmful. The age at which maximal plasma amino acid concentrations in infants given human milk protein supplementation occur coincides with the age of the lowest serum albumin concentrations in infants fed only human milk. This suggests that high plasma amino acid concentrations may hasten albumin synthesis in very low-birth-weight infants.     

Lactose-free milk protein-based infant formula: impact on growth and gastrointestinal tolerance in infants

Lactose, the major carbohydrate in human milk and standard milk-based formulas, provides energy for growth in infants. The use of lactose-free milk protein-based infant formulas has increased in the United States. However, clinical studies of their impact on growth, safety, and gastrointestinal tolerance in infants are limited. Thus, a prospective, blinded, randomized clinical trial was conducted in healthy, normal-term infants fed an experimental lactose-free milk protein-based formula (NoLAC; n = 63) versus a standard commercial lactose-containing milk-based formula (LAC; n = 65) for 112 days. Growth (weight, length, and head circumference) was similar and normal in both groups (weight gain: NoLAC = 31.1 ± 0.9 g/day, LAC = 29.4 ± 0.9 g/day, mean ± SEM; P = .895). Serum biochemistries for both groups were within infants' normal reference ranges. Both groups had comparable tolerance but the NoLAC group had softer stools and lower spit-ups. Thus, the study suggests that absence of lactose in milk-based formula does not adversely affect normal growth in term infants.     

High protein pre-term infant formula: effect on nutrient balance, metabolic status and growth

Several lines of evidence suggest that formula with protein content of 3.0 g/100 kcal does not fully meet the protein needs of very-low-birth weight infants. Our purpose was to compare nitrogen balance, metabolic status and growth in infants fed a standard (3.0 g/100 kcal; RegPro) and high (3.6 g/100 kcal; HiPro) protein infant formula. Infants were fed both formulas, each formula for one week in balanced cross-over design. Metabolic status was monitored throughout. Nutrient balance and plasma amino acids were determined at the end of each week. Data were analysed using a linear mixed model. Eighteen infants were studied. Nine infants received the RegPro and nine received HiPro formula first. Nitrogen intake, absorption and retention were greater with the HiPro formula. None of the infants developed uremia or metabolic acidosis but retinol-binding-protein and weight gain were greater with the HiPro formula. Increased protein accretion paralleled by better weight gain without evidence of metabolic stress indicates that a formula with a protein content of 3.6 g/100 kcal better meets protein needs in these rapidly-growing infants. Further studies are needed to determine whether these short-term outcomes will be translated into long-term benefits.     

Protein and energy intake during weaning. III. Effects on plasma amino acids

Preprandial plasma amino acid concentrations were measured at 5 and 6 months of age in 30 healthy term infants who were either breast-fed ad libitum or fed one of two different formulas (1.9 g of protein per 100 ml with a whey:casein ratio of 50:50; 2.9 g of protein per 100 ml with a whey:casein ratio of 20:80) ad libitum, plus the same supplementary food regimen. The mean plasma concentrations of total amino acids and especially total essential amino acids were higher in the formula-fed infants. Those fed formula also had plasma concentrations of methionine, isoleucine, phenylalanine, leucine, valine, threonine, aspartate, proline, lysine, tyrosine, histidine that exceeded plasma concentrations of breast-fed infants by 2 or more standard deviations. Concentrations of arginine, glutamic acid, glutamine, ornithine, serine, cystine did not differ and taurine was higher in the breast-fed infants. The data indicate that formulas in common use today during weaning (4-6 months) provide excessive protein intakes when compared to the breast-fed control infants. A lowering of protein concentration and a further manipulation of the whey:casein ratio is necessary if plasma amino acid patterns similar to those found in breast-fed infants is to be achieved with artificial feeding.     

Metabolic changes in newborn infants following surgical operations. I. Blood levels of glucose, plasma free fatty acids, alpha-amino nitrogen, plasma amino acid ratio and urea nitrogen.

In 29 newborn infants subjected to surgery for congenital anomalies, the blood glucose, free fatty acid (FFA), amino acid, alpha-amino nitrogen and blood urea levels were observed from the first to the seventh postoperative days. The blood glucose level showed moderate changes in the postoperative period, while FFA decreased significantly. The combined concentration of non-essential amino acids (glycine + glutamine + serine + taurine) and that of essential amino acids (leucine + isoleucine + valine + methionine), their quotient (Whitehead's ratio), as well as the alpha-amino nitrogen level indicated dynamic changes in the postoperative period. The gradual return of blood urea to the preoperative level is explained by the diminished breakdown and the improved excretory function of the kidney following surgical procedures.