Changes in urinary amino acid fractional excretion in neonates undergoing total parenteral nutrition

The paper examines the possible reasons why there was a different weight gain pattern in two groups of sick neonates fed two different amino acid solutions during a prospective double-blind trial of otherwise identical total parenteral nutrition. During the 13-month study period, 14 neonates (eight less than 32 weeks gestation) received Vamin as their amino acid source, and 18 (eight less than 32 weeks gestation) received a new amino acid solution, Paedmin. The older group of neonates gained weight far better when fed Vamin (P less than 0.003), neonates of less than 32 weeks gestation gained weight better when fed Paedmin (P less than 0.004). These differences in weight gain were reflected in differences in plasma amino acid concentration in that the levels were lower in the groups gaining weight less well; and in urinary fractional excretion where the groups gaining weight less well had a markedly higher fractional excretion and total urinary loss of amino acids (P less than 0.001). It is suggested that these differences in amino acid handling of two different amino acid solutions may lead to differences in weight gain.     

Egg and breast milk based nitrogen sources compared.

A nitrogen source based on egg protein (Vamin 9 glucose) and an alternative with an amino acid profile more similar to breast milk (Vaminolact), were compared in 14 parenterally fed infants. Subjects were randomly allocated to receive one or other amino acid solution, but were otherwise given identical diets. At the start of the study the two groups did not differ significantly in postconceptual age, postnatal age, or weight. Over a six day study period on a stable intake of intravenous nutrients there was no significant difference in growth or nitrogen retention between the two groups. Plasma amino acid profiles in those receiving Vamin 9 glucose, however, were frequently abnormal. Notably, mean concentrations of potentially neurotoxic phenylalanine and tyrosine were significantly higher (140% and 420%, respectively) in patients fed Vamin 9 compared with those given Vaminolact. An amino acid solution based on the composition of breast milk protein therefore brings plasma amino acid profiles during parenteral nutrition closer to those found in breast fed infants, and reduces in particular, the risks of hyperphenylalaninaemia and hypertyrosinaemia.     

Decreased cholestasis with enteral instead of intravenous protein in the very low-birth-weight infant

Thirty to 50% of very low-birth-weight infants have parenteral nutrition-associated cholestasis. To test the hypothesis that the incidence of cholestasis would be decreased if parenteral amino acids were avoided and protein given enterally, infants with a gestational age of less than 30 weeks were randomized to two groups. One group received amino acid-free parenteral nutrition and whey protein enterally with added premature infant formula. The control group received standard parenteral nutrition with amino acids and enteral premature formula. At the end of 3 weeks of parenteral nutrition, infants who had a direct serum bilirubin level of greater than 3 mg/dl were considered to have significant cholestasis. Twenty-nine infants required parenteral nutrition for 3 weeks, 17 in the whey group and 12 in the control group. No instances of significant cholestasis were observed in the whey group (0/17), whereas seven of 12 infants (58%) in the amino acid control group had cholestasis (p less than 0.001).     

Vitamin E status in preterm infants fed human milk or infant formula

Vitamin E status was assessed in 36 infants with birth weights less than 1500 gm who were assigned randomly to receive one of three sources of nutrition: milk obtained from mothers of preterm infants (preterm milk), mature human milk, or infant formula. Infants in each dietary group were further assigned randomly to receive iron supplementation (2 mg/kg/day) beginning at 2 weeks or to receive no iron supplementation. All infants received a standard multivitamin, providing 4.1 mg alpha-tocopherol daily. Serum vitamin E concentrations at 6 weeks were significantly related both to type of milk (P less than 0.0001) and to iron supplementation (P less than 0.05). Infants fed preterm milk had significantly higher serum vitamin E levels than did infants fed mature human milk, and both groups had significantly higher levels than did those fed formula. Ratios of serum vitamin E/total lipid were also significantly greater for infants fed human milks than for those fed formula. The addition of iron to all three diets resulted in significantly lower serum vitamin E levels at 6 weeks (P less than 0.05); however, only in the group fed formula was there evidence of vitamin E deficiency. Preterm milk with routine multivitamin supplementation uniformly resulted in vitamin E sufficiency in VLBW infants whether or not iron was administered.     

Relationship of serum bilirubin levels to ototoxicity and deafness in high-risk low-birth-weight infants

During a 4-year period, 12 premature infants, all less than 34 weeks of gestation and all with a bilirubin level above 240 mumol/L (14 mg/dL) were determined to have bilateral sensorineural deafness. In order to to investigate how far the hyperbilirubinemia or any a associated factor might have been a causative factor, all infants of 34 weeks of gestation or less who had a serum bilirubin level above 240 mumol/L were investigated. For a period of 4 years, 99 infants meeting these criteria were classified as high risk or low risk on the basis of perinatal risk factors. Eight of the 22 high-risk infants with birth weight less than 1,500 g, but only two of 43 high-risk infants with birth weight greater than 1,500 g were deaf (P less than .05). The deaf infants were also matched with infants of normal hearing who had similar bilirubin levels and the same number of adverse perinatal factors. The mean duration of hyperbilirubinemia was significantly longer in the deaf infants (P less than .02), and they appeared to have a greater number of acidotic episodes while they were hyperbilirubinemic. These findings suggest that in healthy preterm infants with birth weight greater than 1,500 g, high bilirubin levels carry little risk, whereas a serum bilirubin level greater than 240 mumol/L in high-risk preterm infants with birth weight of 1,500 g or less is associated with a high risk of deafness.     

Essential fatty acid status of the premature infant during short-term fat-free parenteral nutrition

This study was designed to evaluate the effect of fat-free parenteral nutrition on the essential fatty acid status of a group of stable premature infants during the first 10 days of life. Nine infants had a gestational age of less than 32 weeks (Group 1), and 10 infants, 32-34 weeks (Group 2). Five of nine infants in Group 1 and two of 10 infants in Group 2 developed essential fatty acid deficiency (EFAD) (triene/tetraene ratio greater than 0.4). In three infants, EFAD was present by 5 days of age; and in four, between 5 and 10 days of age. The difference in frequency of EFAD between Groups 1 and 2 is statistically significant (p less than 0.05). The development of EFAD as a function of postnatal age could be predicted using a simple regression, y = -0.14 + 0.07x (r = 0.64, p less than 0.0001), where y represents the triene/tetraene ratio and x the postnatal age in days. We conclude that (a) EFAD may develop rapidly in the premature infant; (b) the more immature the infant, the greater the risk of EFAD; (c) the degree of EFAD increases with the duration of fat-free parenteral nutrition.     

Safflower oil emulsion administration during parenteral nutrition in the preterm infant. 2. Effect on triglyceride and free fatty acid levels

During a study to evaluate the effect of a safflower oil emulsion on essential fatty acid status during parenteral nutrition, we also measured plasma triglycerides and plasma free fatty acids (FFA) in a group of preterm infants. Subjects received 0.34 g/kg (group 1) or 0.68 g/kg (group 2) of lipid daily for 5 days. Essential fatty acid status remained normal in both groups, but the changes in plasma triglycerides were greater (p less than 0.025), and hypertriglyceridemia was somewhat more common (p = 0.06) in group 2 than in group 1. Plasma FFA did not differ in either treatment group. However, postinfusion FFA were greater (p less than 0.05) and FFA uptake was less (p less than 0.05) in infants at less than 32 than at 32-34 weeks gestation, but in no instance did postinfusion FFA exceed an FFA/albumin ratio of 6:1. In addition, triglyceride and FFA uptake did not improve during the study, but the changes in plasma triglycerides and FFA were greater (p less than 0.05) at the end than at the beginning of the study.     

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.     

Fortified mothers' milk for very low birth weight infants: results of macromineral balance studies

The mineral adequacy of fortified mothers' milk for very low birth weight (VLBW) infants was tested during their first two postnatal months. Metabolic balance and serum Ca, P, Mg, Na, and K values were evaluated at 2.5 and 6 weeks of life in 32 VLBW infants (less than 1.3 kg). Infants were fed either their mothers' milk fortified with skim and cream components derived from heat-treated, lyophilized mature human milk (FMM) or commercial cow milk-derived formulas. Despite Ca and P concentrations 50% to 100% higher in the fortified human milk than is usual in unfortified human milk, group FMM's Ca and P intakes remained significantly below those fed formula (P less than 0.001). Serum calcium levels and alkaline phosphatase activity were higher and serum phosphorus lower (P less than 0.002) in group FMM, whereas serum levels of magnesium, sodium, and potassium were similar in both groups. Ninety-six-hour urinary excretion of Ca was greater and 96-hour urinary excretion of P was less in group FMM (P less than 0.02). Retention of Ca and P in both groups was significantly below estimates of intrauterine accretion. Mg retention was significantly higher in group FMM (P less than 0.002) despite intakes of Mg significantly below those in infants fed formula. Although intakes of Na were below recommended levels in both groups, by the second balance period all infants demonstrated Na retention that was greater than expected from the sum of estimates of intrauterine accretion and dermal losses. Similar findings were noted for K. Biochemical and balance data indicate that relative to the needs of the VLBW infant, fortified mothers' milk was deficient in Ca and P, but adequate in Mg, Na, and K.     

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.     

Assessment of implementation of a standardized parenteral formulation for early nutritional support of very preterm infants

Introduction Parenteral nutrition (PN) plays an important role in the nutritional support of very preterm newborns. It has been suggested that a high proportion of PN orders could be standardized. In 2002, we implemented in our unit the preparation of three standardized formulations for PN adapted to the nutritional requirements of premature infants <32 weeks. Following this change of practice, a retrospective observational study was conducted to evaluate the relevance of the implemented standardized PN regime. Twenty premature inborn infants <32 weeks gestation who had received standardized (STD) PN in 2003 were matched for 20 infants who had received individualized (IND) PN in 2001. Adequacy of nutrition was assessed by comparing daily intravenous nutrient intake and biochemical parameters during the first week. Amino-acid intakes on day 3 were higher in the STD group (1.5±0.2 g/kg/d vs. 0.9±0.5, p<0.001), and the calcium phosphate intakes were better balanced. The cumulated intake of amino acids for the first week was greater in the STD group (+20% ; p=0.0003). Biochemical parameters were similar in both groups. Insulin infusions were less frequent in the STD group (p<0.06). Conclusion Standardized parenteral formulations provided higher early intakes of amino acid and glucose, a better calcium phosphate ratio, and a greater amount of amino-acid intakes during the first week while maintaining the same biochemical parameters. This strategy forms part of an approach concerning quality control and the respect of good professional practice for the preparation of parenteral nutrition solutions.     

34 周以下适于胎龄及小于胎龄早产儿出生 2 周内 蛋白质、能量摄入及体质量变化

目的了解34周以下早产适于胎龄儿(AGA)和小于胎龄儿(SGA)生后蛋白质、能量摄入量以及体质量z评分的变化情况。方法回顾收集2012年1月至2014年12月入院的314例早产儿,比较268例AGA和46例SGA早产儿生后2周内蛋白质、能量摄入情况和体质量变化。结果 SGA组住院时间、肠外联合肠内营养时间、全肠内营养时间、达足量喂养时间均较AGA早产儿长,差异有统计学意义(P??0.05);SGA组生后第4、8、12天能量摄入量明显低于AGA组,SGA组生后第6、8天总蛋白质摄入量明显低于AGA组,差异均有统计学意义(P??0.05);SGA组日平均体质量增长量大于AGA组,差异有统计学意义(P??0.05);AGA组与SGA组生后2周内体质量z评分均逐渐远离中位水平,且SGA组2周时体质量z评分低于AGA组(P??0.05)。结论胎龄??34周的SGA早产儿恢复出生体质量后的生长速率快于AGA早产儿,存在一定的追赶生长;但SGA、AGA早产儿的生长均有待提高。     

Human milk and preterm formula compared for effects on growth and metabolism.

Metabolic tolerance to a ''premature formula'' feed was studied in a group of small immature infants, mean (SD) gestation 27.8 (1.4) weeks. Ten infants weighing 880-1295 g at the time of the study were fed on SMA low birthweight formula for a mean (SD) of 23.5 (5.5) days and were compared with 10 who were fed on expressed breast milk for 25.8 (6.1) days. The infants were well matched for weight, gestation, and postnatal age at the time of the study and were receiving full enteral feeds. They were investigated by balance techniques and plasma sampling on at least two occasions. Ten larger infants weighing 1330-1740 g and being fed on the same formula feed were also studied as an additional control group. Formula fed infants retained more nitrogen and gained weight faster. Plasma phosphorus concentrations were higher in the group fed on the formula feed, and alkaline phosphatase activity was lower. There were no significant differences in plasma concentrations of urea, electrolytes, or albumin or in acid base status. Taurine and arginine concentrations were higher in the group being breast fed, but there were no other significant differences in plasma amino acids, and no toxic concentrations occurred after either feed. The results of this study show that this formula (and presumably other feeds of similar composition) seem to be metabolically safe for the smallest infants.     

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.     

Macromolecular Absorption in Preterm and Term Infants

ABSTRACT. Human o-lactalbumin (α-LA) has been used as a marker for measuring macromolecular absorption. The serum concentration of human α-LA after a human milk feed has been studied in 32 healthy very low birthweight infants (VLBW), fed human milk (gestational age 26–32 weeks) and in 56 term, breast-fed infants, age 3–140 days. At 31 weeks of gestation the serum concentration of human α-LA was more than 10 times higher (mean value 3000 and median value 2101 μg/1 serum/1 human milk/kg body weight, n = 11) than in the term infants aged 3–30 days (mean value 257 and median value 152, n = 29). The serum concentration of o-LA decreased with increasing maturity in the VLBW-infants. At a postconceptional age of 37 weeks the values were similar (mean value 200 and median value 99, n = 8) to those found for term infants during the first month. In the term infants a decreasing absorption of α-LA was found with increasing postnatal age.     

Serum concentrations of growth hormone, insulin, free thyroxine, thyrotropin, and cortisol in very-low-birth-weight infants receiving total parenteral nutrition

Serum concentrations of growth hormone, insulin, free thyroxine, thyrotropin, cortisol, and glucose were measured during four time periods (0 to 4, 5 to 11, 12 to 18, and greater than or equal to 19 days of life) in 16 mechanically ventilated very-low-birth-weight infants (mean [+/- SD] birth weight, 1017 +/- 196 g) receiving total parenteral nutrition and in 21 very-low-birth-weight infants not requiring mechanical ventilator support (mean [+/- SD] gestational age, 30 +/- 1.7 weeks; mean [+/- SD] birth weight, 1149 +/- 210 g) fed enterally. There were no significant differences in the serum concentrations of the hormones or in the glucose levels between the two groups at any time interval. Present data demonstrate no significant difference in the serum concentration of glucose, insulin, growth hormone, cortisol, free thyroxine, and thyrotropin between very-low-birth-weight infants fed enterally and those maintained on a regimen of total parenteral nutrition.     

Early neonatal hyperkalaemia in the extremely premature newborn infant

The incidence of hyperkalaemia in 43 consecutive infants born at less than 28 weeks gestation and cared for in our neonatal intensive care unit was documented. Plasma K levels were related to indices of renal function as well as to the degree of illness in the infants. The mean gestational age was 26.0 weeks (range 24-27 weeks) and the mean birthweight was 815 g (range 395-1170 g). Twenty-six of the infants (60%) had at least one plasma K greater than 5.5 mmol/L and 13 (30%) had a maximum plasma K greater than 7 mmol/L. The mean postnatal age at which the plasma K exceeded 7 mmol/L was 25 h (range 10-39 h). Five infants with plasma K greater than 7 mmol/L developed cardiac arrhythmias and four died of this complication. Only one infant had a large intraventricular haemorrhage. Only two of 16 infants with an initial plasma K less than 5 mmol/L had a maximum plasma K greater than 7 mmol/L, compared with eight of 10 with an initial plasma K greater than 6 mmol/L (P less than 0.005). Plasma K also correlated directly with plasma urea (P less than 0.001) and plasma creatinine (P less than 0.025), and inversely with urine volume (P less than 0.05). Plasma K did not correlate with K intake, arterial pH, presence of asphyxia, severity of respiratory illness, gestation or birthweight. The rapidity with which the plasma K concentration reached potentially hazardous levels in some infants makes it imperative to measure plasma K within 6 h of birth and to continue to monitor levels at least every 6 h for the first 48 h in all infants born at less than 28 weeks gestation.     

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.     

Serum plasminogen and lung surfactant in the respiratory distress syndrome

Plasminogen, total protein, and surface-active material were measured in amniotic fluid in 112 pregnancies at 11-42 weeks' gestation. In 65 of these pregnancies, cord blood was also analyzed for serum plasminogen and total protein. Plasminogen was detected in 25 of 114 amniotic fluid samples, and 23 came from pregnancies of less than 37 weeks' gestation. Plasminogen was found in 15 of 32 amniotic fluid samples from pregnancies with complications, but only in 10 of 80 "uncomplicated" pregnancies. The mean cord serum plasminogen was relatively constant in births or abortuses of 17 to 30 weeks' gestation, but was present in increasing amounts in births of gestational ages from 30 to 40 weeks. The concentration of plasminogen in cord serum was directly related to the cord total protein (r = 0.7513, P less than 0.001). The cord plasminogen concentration was significantly higher in infants with a positive foam stability test (5.6 +/- 0.3 mg/100 ml) than in the combined group of infants with negative and intermediate tests (4.3 +/- 0.16, P less than 0.005). However, infants with a positive foam stability also had a significantly greater gestational age than infants with a negative or intermediate foam stability test. With one exception, infants with a low cord plasminogen (below 4 mg/100 ml) developed respiratory distress syndrome (RDS) only if amniotic fluid surfactant was low. The data suggest that low levels of serum plasminogen are correlated with severe lung disease only in the presence of surfactant deficiency.     

Longitudinal follow-up of height up to five years of age in infants born preterm small for gestational age; comparison to full-term small for gestational age infants

OBJECTIVE: This aims to conduct a comparative study of the height catch-up rate in preterm small for gestational age (SGA) infants during early childhood by gestational age and identify the factors affecting short stature in comparison to full-term SGA infants. METHODS: 449 SGA infants (214 full-term infants, 73 infants with gestation of less than 32 weeks, and 162 infants with gestation of more than 32 weeks but less than 37 weeks) from 25 institutions in Japan were assessed for catch-up (> or = -2SD) rate in growth by measuring for length/height at 1 year, 3 years and 5 years of age and the risk factors for no catch-up (< -2SD) at 5 years. RESULTS: The overall length/height catch-up rate was 68% at 1 year, 89% at 3 years and 88% at 5 years. The catch-up rate at 3 and 5 years of age in the group with gestation of less than 32 weeks had a rate of 74%, which was significantly less than the other two groups (approximately 90%). A significant factor associated with short stature at 5 years in the group with gestation of less than 32 weeks was the lower length SD score at time of birth, and for preterm infants born more than 32 weeks of gestation and full-term infants, significant factors were the lower maternal height and head circumference at birth. CONCLUSION: SGA infants born less than 32 weeks of gestation had a higher risk of no catch-up and different factors affecting catch-up compared to preterm SGA infants of gestation more than 32 weeks and full-term SGA infants.