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.     

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.     

Postprandial plasma amino acids in preterm infants: influence of the protein source

Preprandial plasma amino acid concentrations have been used extensively as a marker of the nutritional value of dietary proteins in preterm infants. This study investigated the postprandial plasma amino acid profiles of preterm infants fed with different dietary proteins at similar protein intakes during the first weeks of life. In 12 preterm infants, pre- and postprandial plasma amino acid concentrations were measured before the removal of an indwelling central venous catheter placed for parenteral nutrition. All infants received breast milk until the time of study. At the start day of the study, infants were randomized to receive a test meal of 10 ml/kg, either of breast milk fortified with breast milk protein to reach a protein content of 2.0 g/dl or of a bovine milk preterm formula with a protein content of 2.0 g/dl (whey/casein ratio 60/40). Five samples of 100 microl blood were obtained immediately before and 15, 30, 45 and 60 min after the test meal. The plasma amino acid analysis was performed by a reversed-phase high-performance liquid chromatography based on o-phthaldialdehyde/2-mercaptoethanol pre-column derivatization. In both groups, the plasma amino acid concentrations increased within the first 30 min and the levels did not return to the preprandial baseline during the observation period. Fifteen minutes after the test meal, the plasma levels of all essential amino acids with the exception of histidine were higher in the bovine milk formula fed infants than in the fortified breast milk fed infants. The sum of plasma essential amino acid levels found in the formula fed infants were significantly (p < 0.05) higher than the levels found in the fortified breast milk fed infants at 15, 30 and 45 min. The kinetics of individual amino acids were influenced by the different quality of the protein even when the intakes in the groups were similar, as demonstrated for histidine and phenylalanine. The data indicate that postprandial plasma amino acid concentrations depend significantly on the dietary amino acid source and cannot simply be calculated from the amino acid composition of dietary proteins. Therefore, postprandial plasma amino acid concentrations should be included in the nutritional evaluation of dietary proteins in preterm infants.     

Protein quality of human milk fortifier in low birth weight infants: Effects on growth and plasma amino acid profiles

Serum preprandial essential amino acid, urea and prealbumin concentrations, and growth rates were studied in appropriate for gestational age low birth weight infants fed one of three regimens: (1) human milk enriched with human milk protein (n=17); (2) bovine whey protein hydrolysate (n=18; and (3) a mixture of bovine proteins, peptides and amino acids designed to have an amino acid composition close to that of human milk proteins (n=18). Energy and nitrogen intakes were similar in all groups. Growth rates and gross metabolic responses did not differ between the feeding groups. There were also no differences in the amino acid profiles between those infants fed human milk protein fortifier and mixed bovine protein fortifier. Infants fed the whey fortifier had significantly higher threonine concentrations in comparison to those fed exclusively human milk protein (287±63 mol/l vs 168±26 mol/l) whereas the levels of some other essential amino acids (i.e. valine, leucine, lysine, histidine, phenylalanine and tryptophan) were lower. The results indicate that growth rates and gross metabolic indices do not depend on the protein quality of human milk fortifiers. However, the addition of well balanced mixtures of bovine proteins to human milk results in amino acid profiles similar to those observed in LBW infants fed similar amounts of human milk proteins.     

Changes in protein turnover after the introduction of parenteral nutrition in premature infants: comparison of breast milk and egg protein-based amino acid solutions.

Rates of protein turnover were measured in 20 infants receiving either Vamin Infant (group A) or Vamin 9 glucose (group B) as the amino acid source in total parenteral nutrition. A constant infusion of L-[1-13C]leucine was used to measure whole body leucine flux, and leucine oxidation rates were derived from measurements of total urinary nitrogen excretion. Infants were first studied when receiving only i.v. glucose and again on each of the next 4 d as total parenteral nutrition was gradually increased to a maximum of 430 mg nitrogen/kg/d and 90 nonprotein kcal/kg/d. Net protein gain and protein synthesis and breakdown rates increased progressively for all infants taken together over the study period as i.v. nutrition was increasing (p less than 0.001). There were no differences between groups in the changes in net protein gain and rates of protein synthesis and breakdown throughout the study period. Nitrogen retention on d 5 for the two groups was similar (60 +/- 16% and 67 +/- 11% in groups A and B, respectively). In a subgroup of infants, measurements were repeated on d 8, when the intake had been constant for 3 d. Protein retention was the same as on d 5, but both synthesis and breakdown were increased. It is concluded that rates of protein turnover increase significantly in response to increasing i.v. nutrition and that this elevation was not influenced by the composition of the amino acid mixture given.     

A double blind comparison of a new paediatric amino acid solution in neonatal total parenteral nutrition

All infants requiring parenteral nutrition over a continuous 13-month period were allocated to receive either Vamin or a new paediatric amino acid solution, Paedmin, as their protein source in a double blind prospective study. Those of 32 weeks gestation and less gained weight more rapidly when fed Paedmin than Vamin (P less than 0.004), but there were significant changes in liver function after 14 days nutrition. Babies of 33 weeks gestation and greater gained weight more rapidly when fed Vamin than Paedmin (P less than 0.003) but without liver function changes. There were no differences in the rate of head growth. Amino acid analysis of serum and urine showed a greater urinary loss of amino acids for a given serum concentration in babies of 32 weeks and less for both nutrition groups. The apparent benefit of Paedmin in the immature group of infants must be further evaluated and weighed against changes in liver function.     

The effects of surgery on the nitrogen metabolism of parenterally fed human neonates

Nitrogen retention and rates of whole body amino nitrogen flux, protein synthesis, and breakdown were measured in 18 neonates during the 72 h immediately postsurgery. The infants were all intravenously fed with a crystalline amino acid source (Vamin), glucose, and Intralipid The infants were divided into two groups based on amino acid intake: either 2.3 SD 0.4 g or 3.9 SD 0.5 g/kg/day. Nonprotein energy intakes were similar and averaged 81 kcal/kg/day. Group A (n = 11) retained 145 SD 110 mg N/kg/day, whilst group B (n = 7) retained 315 SD 93 mg N/kg/day (p less than 0.001). There were no differences seen in flux, synthesis or breakdown. However, group B had significantly higher net protein synthesis rates (synthesis-breakdown) (p less than 0.01). The improved nitrogen utilization in group B was achieved principally by a reduction in endogenous protein breakdown. There were no differences between the two groups in urinary creatinine or 3-methylhistidine excretion. Since these two parameters reflect skeletal muscle turnover the differences between groups in nitrogen retention and turnover appear to be mediated through visceral protein.     

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.     

Dietary protein source and plasma lipid profiles of infants

Total cholesterol and triglyceride concentrations were measured in plasma samples taken at 4 and 8 weeks of age from 40 full-term infants who had been fed either human milk or one of three formulas containing casein-to-whey ratios of 82:18, 66:34, or 50:50 to investigate whether dietary protein influenced the development of plasma lipid profiles. Infants fed the formula with the casein-to-whey ratio of 82:18 had significantly higher plasma cholesterol levels at both 4 and 8 weeks of age compared with other groups of infants (P less than .05). Infants fed the high-casein formula also showed an increase in plasma cholesterol levels with time (P less than .001). Plasma triglyceride concentrations decreased as concentration of casein decreased (P less than .05) among the formula-fed groups and increased with time. Infants fed human milk had plasma triglyceride concentrations similar to those infants who had been fed the 82:18 formula at 4 weeks of age; however, triglyceride concentrations eventually fell and were similar to those concentrations in infants who had been fed the 50:50 formula at 8 weeks of age. Results indicate that constituent lipids of human milk or formulas were not determining factors for changes observed in plasma cholesterol levels and triglyceride concentrations among groups. Since formulas differed only in proteins and their constituent amino acids, further investigation of the impact of dietary protein (amino acids) on development of blood lipid profiles in infants is warranted.     

Effect of amino acid composition of parenteral solutions on nitrogen retention and metabolic response in very-low-birth weight infants

To evaluate the influence of amino acid preparations on the metabolic response of parenterally fed immature newborn infants, nitrogen retention and plasma amino acid concentrations were compared in very-low-birth-weight infants given two parenteral regimens differing only by the composition of the infused amino acids (Travasol 10% blend B and Vamin 7%). The intakes of fluid, nitrogen, and calories were comparable. The nitrogen retention was 72% +/- 7% with Vamin and 65% +/- 6% with Travasol. The differences in plasma amino acid concentrations were consistent with the composition of the amino acid solutions. During the infusion of Vamin the increased intake of aromatic amino acids resulted in high plasma levels of tyrosine (256 +/- 233 mumol/L, range 67 to 894 mumol/L). The infusion of Travasol resulted in high plasma levels of methionine (114 +/- 39 mumol/L, range 53 to 260 mumol/L) and an elevated load of glycine, which was accompanied by an abnormally high urinary loss of this amino acid. Despite these metabolic imbalances, the growth rate over the whole study was adequate. These results emphasize the importance of the composition of amino acid solutions on the metabolic response of the very immature preterm infant.     

Biotin and carnitine deficiency due to hypoallergenic formula nutrition in infants with milk allergy

Amino acid formulas and hydrolyzed formulas given to infants in Japan with milk allergies theoretically contain little, if any, biotin and carnitine. We assessed biotin and carnitine insufficiency in six infants with milk allergy who were fed amino acid formulas and/or hydrolyzed formulas, by measuring urine 3‐hydroxyisovaleric acid (3‐HIA) and serum free carnitine (C0), respectively. All patients presented with elevated urine 3‐HIA and lowered serum C0 compared with post‐menstrual age‐matched infants who were fed breast milk or standard infant formulas. Supplementation with biotin and l ‐carnitine immediately improved the insufficiency. Care should be taken to avoid biotin and carnitine deficiency in allergic infants fed amino acid or hydrolyzed formulas.     

A new breast milk supplement for preterm infants

Objective : To assess the effect of a new formula (Prenan), which contains n-3 and n-6 long-chain polyunsaturated fatty acids (LC PUFA) on the fatty acid profile of preterm infants.
Methodology : Plasma fatty acids were measured in 61 preterm infants at term by gas liquid chromatography. In 20 of these infants, paired samples were collected and changes in fatty acids with time analysed.
Results : Plasma docosahexaenoic acid (DHA) levels were higher in those who had been fed expressed breast milk (EBM) ±/or Prenan compared with those fed standard formula ± EBM, P <0.05. The plasma arachidonic acid (AA) levels of infants fed Prenan were not different to those fed EBM, both groups achieving higher levels than infants fed standard formula, P <0.05. Further, paired analysis demonstrated that DHA levels increased in infants changed from standard formula to Prenan to levels equal or higher than those of fully breast-fed infants ( P <0.01), whereas DHA levels remained unchanged with time in all other groups.
Conclusions : The fatty acid composition of Prenan enables preterm infants fed formula to have plasma DHA and AA levels similar to those of infants fed breast milk and consequently different to those of infants fed standard formula. Prenan is an appropriate supplement to breast milk for preterm infants in that it provides LC PUFA as well as additional phosphorus and protein without exposing the infant to intact cows milk protein.     

Intake and growth of breast-fed and formula-fed infants in relation to the timing of introduction of complementary foods: the DARLING study

We examined if the timing of introduction of solid foods was related to growth, intake, morbidity, activity or motor development among infants either breast fed or formula fed until 12 months of age. Breast-fed infants given solids before 6 months of age (earlysol) consumed less breast milk at 6 and 9 months of age than those given solids 6 months (latesol); thus total energy intake did not differ between groups. Z scores for weight, length and weight-for-length at 1–18 months did not differ between groups. Latesol infants gained less weight from 6 to 9 months but not during any other interval. Neither activity level nor morbidity differed between groups, but several developmental milestones occurred earlier in the earlysol versus the latesol group, probably due to reverse causation. Among formula-fed infants, timing of introduction of solid foods was not related to intake, growth, activity or morbidity. We conclude that solid foods given before 6 months of age generally replace the milk source among breast-fed but not formula-fed infants.     

Protein supplementation of human milk for the nutrition of VLBW-infants: human milk protein vs. meat protein hydrolysate

In 25 very low birth weight infants appropriate for gestational age the influences of different human milk (HM) preparations on weight gain, gross indices of nitrogen metabolism and energy balance were studied during the second month of postnatal life. HM was fortified either by HM-protein (HMP) or by an enzymatic meat protein hydrolysate (PH) to protein concentrations between 1.5 and 1.7 g/100 ml. The caloric densities of both HM preparations were similar between 62 and 68 kcal/100 ml. There were no differences in weight gain (MM + HMP: 18.6 +/- 3.4 g/kg/day; HM + PH: 16.5 +/- 4.1 g/kg/day), nitrogen retention (HM + HMP: 31.5 +/- 3.1 mmol/kg/day; HM + PH: 30.0 +/- 3.2 mmol/kg/day), and the preprandial estimated essential amino acid profiles between the both feeding groups. In contrast the serum concentrations of alpha-amino-nitrogen 60 minutes postprandially were elevated in the infants fed HM + PH in comparison to the infants fed HM + HMP. This high postprandial amino acid concentrations in serum in the group fed HM + PH were accompanied by increased bile acids concentrations in serum, higher renal amino acid excretion and increased fecal fat losses. The results suggest that due to the more rapid intestinal absorption of amino acids from PH than from HMP the concentrations of amino acids increase postprandially which results in a detectable increase of the newborn cholestasis in these infants. Nevertheless, the scale of these metabolic responses to feeding protein hydrolysates is small and without detectable influences on nitrogen retention or weight gain.     

Indices of protein metabolism in term infants fed either human milk or formulas with reduced protein concentration and various whey/casein ratios

Hyperaminoacidemia is evident in infants fed either whey-dominant or casein-dominant formula containing 2.2 g protein/100 kcal. We assessed protein metabolism in infants fed formulas with reduced protein contents and various whey/casein ratios. Term infants (n = 40) received either human milk or formula containing 1.8 g protein/100 kcal and whey/casein ratios 18:82, 34:66, or 50:50. At ages 4 and 8 weeks, growth indices and mean serum concentrations of retinol binding protein, albumin, total protein, and serum urea nitrogen were similar, as were mean plasma concentrations of total amino acids, total essential amino acids, and their ratio. Compared with infants fed human milk, those fed formula had plasma concentrations similar for valine, lysine, arginine, tyrosine, histidine, threonine, and free and total cyst(e)ine; elevated for phenylalanine, methionine, and citrulline; and depressed for taurine and tryptophan. Except for leucine, mean plasma amino acid values varied similarly among formula groups despite differences in intakes. Our data indicate that feeding formulas providing 1.8 g protein/100 kcal results in many indices of protein metabolism characteristic of human milk feeding. However, certain differences are noted, suggesting the need for further manipulation of specific amino acid patterns of infant formulas.     

Growth and metabolic responses in low-birth-weight infants fed human milk fortified with human milk protein or with a bovine milk protein preparation

Unfortified human milk does not normally provide enough protein to secure maximal growth in low-body-weight (LBW) infants. Due to the practical difficulties in obtaining human milk protein (HMP), a bovine milk protein preparation (BMP) was designed by computer calculation to contain as close as possible the amino acid composition of the nutritionally available human milk proteins. Twenty-one AGA, LBW infants (BW of 1,180 to 1,600 g, GA of 27 to 33 weeks) were randomly assigned to be fed HM enriched either with HMP (9 infants) or BMP (12 infants). When full volume intake (170 ml/kg/day) was reached, the protein intakes were 3.6 +/- 0.5 and 3.3 +/- 0.3 g/kg/day, respectively, in the two diet groups. During the study period of 24 days, the infants achieved intrauterine or better weight gains: 32.9 +/- 3.3 g/day (17.7 +/- 1.9 g/kg/day) in the HMP group and 34.7 +/- 7.3 g/day (18.3 +/- 3.5 g/kg/day) in the BMP group. Serum urea nitrogen, acid-base status, and albumin values were normal and similar in both groups of infants. Plasma concentrations of total essential and total amino acids at the end of the study were 3,999 and 1,539 mumol/L and 3,899 and 1,422 mumol/L in the HMP and the BMP groups, respectively. The concentrations of all individual plasma amino acids were similar in both feeding groups. These results show that feeding human milk fortified with a modified bovine milk protein preparation produces satisfactory growth and a plasma amino acid profile similar to that found in LBW infants fed exclusively human milk protein at similar intakes.     

Individualized protein fortification of human milk for preterm infants: comparison of ultrafiltrated human milk protein and a bovine whey fortifier.

BACKGROUND: To improve the nutritional management of pre-term infants, a new individualized human milk fortification system based on presupplementation milk protein analyses was evaluated. METHODS: In an open, prospective, randomized multicenter study, 32 healthy preterm infants (birth weights, 920-1750 g) were enrolled at a mean of 21 days of age (range, 9-36 days) when tolerating exclusive enteral feedings of 150 ml/kg per day. All infants were fed human milk and were randomly allocated to fortification with a bovine whey protein fortifier (n = 16) or ultrafiltrated human milk protein (n = 16). All human milk was analyzed for protein content before fortification with the goal of a daily protein intake of 3.5 g/kg. During the study period (mean, 24 days) daily aliquots of the fortified milk were obtained for subsequent analyses of the protein content. RESULTS: Both fortifiers were well tolerated, and growth gain in weight, length, and head circumference, as well as final preprandial concentrations of serum urea, transthyretin, transferrin, and albumin were similar in both groups. The ultimate estimated protein intake was equivalent in both groups (mean 3.1+/-0.1 g/kg per day). Serum amino acid profiles were similar in both feeding groups, except for threonine (significantly higher in the bovine fortifier group) and proline and ornithine (significantly higher in the human milk protein group). CONCLUSIONS: Protein analyses of the milk before individual fortification provides a new tool for an individualized feeding system of the preterm infant. The bovine whey protein fortifier attained biochemical and growth results similar to those found in infants fed human milk protein exclusively with the corresponding protein intakes.     

AMINO ACIDS IN PARENTERAL NUTRITION OF PRETERM INFANTS

ABSTRACT. Parenteral feeding of preterm infants has been accepted as an alternative form of nutrition in those infants unable to accept oral feeding. The amount of amino acid nitrogen and the composition of the amino acid solution to be used, however, have not yet been defined. The amino acid intake and the plasma amino acid concentration of three groups of preterm infants were compared. Twenty-three infants were fed parenterally. Of these, 16 were studied during the first week of life (group I) and 7 during the second week (group II). A control group of 9 infants fed with oral formula was also studied in the second week (group III). In general, plasma amino acid concentrations in the parenterally fed groups were higher than in the orally fed group, in spite of a lower intake. Comparison of the amino acid intake of groups I and II relative to group III, with the plasma amino acid concentrations of groups I and II relative to group III, revealed a rather constant ratio with the exception of tyrosine and aspartic acid, where higher values were found. It is concluded that further increase in the amino acid nitrogen in parenteral feeding of preterm infants requires a more adapted preparation.     

THE METABOLIC CONSEQUENCES OF HUMAN MILK AND FORMULA FEEDING IN PREMATURE INFANTS

Abstract. Schultz, K., Soltész, G. and Mestyán, J. (Department of Paediatrics, University Medical School, Pécs, Hungary). The metabolic consequences of human milk and formula feeding in premature infants. Acta Paediatr Scand, 69: 647, 1980.—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.     

Partial parenteral feeding in infants with special reference to the amino acid levels (author's transl)]

12 infants aged between 6 weeks and several months were partially fed for a period of three days parenterally with a 6% amino acid solution adapted to breast milk as well as with an electrolyte solution with 10% glucose. The amino acid levels in the plasma were determined daily in the blood of fasting blood after an infusion period of 20 hours and after an interval of four hours. All the amino acids examined during the period of the study, revealed good homeostasis.