早期输注大剂量氨基酸对改善早产儿氮平衡的有效性研究

目的评价早期输注大剂量氨基酸对改善早产儿氮平衡的有效性。方法将2010年1月—2010年12月间出生24 h内体质量1 000～2 000 g入住新生儿重症监护室(NICU)接受肠道外营养治疗的早产儿,随机分为两组。实验组于生后24 h内输注氨基酸2.0 g/(kg.d)起,每天增加0.85 g/kg,预期峰值3.7 g/(kg.d);对照组于出生24 h内输注氨基酸0.5 g/(kg.d)起,每天增加0.5 g/kg,预期峰值3.7 g/(kg.d)。结果实验组早产儿生后第1周均处于正氮平衡;对照组早产儿生后前3 d均处于负氮平衡;实验组早产儿第1周每天平均氮平衡值均大于对照组,差异有统计学意义(P均<0.01)。实验组早产儿体质量下降百分比少于对照组,差异有统计学意义(P<0.05);头围增长大于对照组,差异有统计学意义(P<0.05);达到肠内营养418.4 kJ/kg的天数、恢复出生体质量的天数和体质量达到2 000 g的天数均少于对照组,差异有统计学意义(P均<0.05)。结论早产儿生后24 h内即开始输注大剂量氨基酸(2.0 g/kg)能显著改善氮平衡,增加喂养耐受性和促进早产儿生长。     

Metabolic acidosis, nitrogen balance and weight gain in preterm infants.

Nitrogen balance, urinary NAE and the acid base parameters in the blood of 15 male preterm infants with birth weights of 1000--2370 g (mean 1715 g) and gestational age of 29--37 weeks (mean 33.3 weeks) were determined weekly, in the first six weeks of life. The sum of NAE plus acid retention, as "total acid", was used to investigate the relationship between nitrogen balance, weight gain and acid-base homeostasis. During the first three postnatal weeks, nitrogen intake, urinary and faecal loss of nitrogen as well as the nitrogen retention were rapidly increasing. Later, urinary excretion continued to rise, the intake remained unchanged and as a result, the amount of retained nitrogen decreased slightly. Urinary NAE was steadily increasing to reach the maximum of 2.8 mEq/kg by the fourth week. Acid retention was the most pronounced in the second and third week, thereafter it fell until the end of the study. The importance of NAE relative to acid retention was continuously increasing throughout the observation period. The "total acid" increased gradually and reached its peak value in the third week of life. Subsequently a continuous fall was seen. During the first three weeks of life there was a significant positive correlation between "total acid" and nitrogen intake and urinary nitrogen extraction. Since the increase in "total acid" went parallel with the increasing nitrogen retention, the latter may be assumed to be an additional factor in producing acidosis. Calculated per 100 mg nitrogen ingested, retained or excreted with urine, "total acid" was decreasing with the increasing rate of weight gain. This indicates that the growth process -- irrespective of the postnatal development of renal H+ handling -- is also involved in the elimination of acids.     

Plasma amino acids in supplementary parenteral nutrition of preterm infants. Effect of different quantities of amino acid infusion and comparison with enteral feeding

The present investigation aims to determine quantity and quality of the amino acid (AA) solution to be used in supplementary parenteral nutrition (SPN). We established the plasma AA concentrations of preterm infants (birthweight 1160-1940 g, mean 1540; gestational age 29-30 weeks, mean 32) divided into three groups. Group I (n = 11) and group II (n = 12) were put on a standardised SPN regimen starting with an intravenous supply of 2.5 resp. 1.5 g AA/kg/day. Infants of group III were formula-fed, and served as controls. A total of 231 aminograms was obtained during the first two weeks of age. Comparison of groups I and II to group III revealed plasma accumulation of six AA in group I. Supplementation in group II resulted in a normal pattern, except alanine, proline, and methionine. However, only deviations of proline and methionine may be judged as imbalances, and lowering in composition may be considered. We conclude that the low intravenous AA intake employed in group II may be preferred in SPN of preterm infants.     

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.     

Higher urinary excretion of essential amino acids in preterm infants fed protein hydrolysates

Aim: Protein hydrolysates have been introduced in preterm formulae, but it is not clear whether they are needed for the feeding of preterm infants. We designed a randomized, controlled trial to test the effects of a preterm formula with hydrolysed cow's milk proteins on short-term growth and urinary and plasma amino acids levels. Methods: Infants with a birthweight ≤1750 g and gestational age ≤34 wk fed a conventional preterm infant formula (formula B) or a hydrolysed formula (formula A). Weight was measured daily; length, head circumference, mid-arm circumference and total skinfold thickness were measured weekly. Blood and urine were analysed for amino acid concentrations at start, 14 and 28 d. Results: Twenty-one infants met the criteria for randomization. The daily feeding volumes were: formula A 172.8±5.6 vs formula B 170.1±2.8 ml/kg/d. Infants fed with formula A showed slower weight gain (17.4±3.4 vs 20.5±3.3 g/kg/d; p=0.045) and lower mean change in Z-scores for weight (-0.18±0.16 vs 0.00±0.09; p=0.009) and for head circumference (-0.06±0.13 vs 0.06±0.13; p=0.049). After 14 d, infants receiving formula A had statistically significant higher urinary levels of essential amino acids compared to infants receiving formula B.

Conclusion: Our results support the hypothesis of less nutritional value of hydrolysed versus conventional preterm formulae. Higher renal excretion of essential amino acids may be one of the mechanisms involved. These findings must be confirmed by further studies with larger sample sizes and protein hydrolysates with different degrees of hydrolysis.     

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.     

改善早产儿消化道动力的途径

<正> 早产儿消化系统不成熟,吸吮、吞咽及其协调能力差,且胎龄愈小,吸吮力愈差,甚至无吞咽反射,贲门括约肌松弛,易发生呕吐、反流、腹胀、腹泻。坏死性小肠结肠炎(neonatal necrotizing enterocolitis.NEC)在早产儿中发病率较高。改善早产儿消化道动力的研究很多,现综述如下。     

Physiology of fluid balance in preterm infants

One of the most important lessons learned in caring for sick newborn infants is the vital importance of accurate fluid balance. Preterm infants are particularly vulnerable because of the enoumous potential for fluid loss through the skin and the immaturity of renal function. This review considers these points in detail with reference to the practical implications they have when planning the fluid therapy of preterm infants.     

Effect of supplementation of preterm formula with long chain polyunsaturated Fatty acids on mineral balance in preterm infants

BACKGROUND: Incorporation of long chain polyunsaturated fatty acids (LCP) into formulas may interfere with mineral metabolism. We investigate mineral balance in preterm infants who were fed a formula with LCP. METHODS: Infants were randomized in a double-blind manner, 20 infants in each group, to receive a formula with LCP (F+LCP) or without LCP (F) for 30 days. Plasma levels (at the beginning and after 30 days) and nutritional balance (after 1 week) for Ca, P, Mg, Zn, and Cu were obtained for all infants. RESULTS: Groups were similar regarding birth weight, gestational age, weight, and corrected age at study start. During the 30-day study period, the groups had comparable milk intake and reached similar and satisfactory weight gains and longitudinal growth. Within each group, there was no change in plasma mineral concentrations over the course of the study, and there were no differences at each time point between groups. All values were within the normal range for age. No differences in mineral balance were detected between the F and F+LCP groups, with both groups demonstrating comparable intake, net retention, and fecal losses of each mineral. CONCLUSIONS: Adding a content of LCP blend similar to that of human milk to a preterm formula caused no disturbance in Ca, P, Mg, Zn, or Cu nutritional balance.     

早期大剂量氨基酸在早产儿静脉营养中的研究进展

随着早产儿存活率的日益提高,其日后的营养状况逐渐被关注.特别是极低和超低出生体重儿,由于宫内营养不足,出生后对热卡需求高,单纯经胃肠道喂养往往不能满足其营养和代谢需求,静脉营养是其获取能量的重要方法.近年来,国外已普遍开展了静脉大剂量氨基酸的早期应用,并发现该方法不仅安全,而且对改善早产儿生长和营养状况是有效的.因此,生后迅速建立营养支持对追赶生长是十分必要的.     

Early administration of indomethacin to preterm infants.

Indomethacin (0.2 mg/kg) or saline was given intravenously during the first 24 hours to 50 preterm infants in a double blind controlled trial. Eight of the control group later required treatment with indomethacin for clinical signs of left to right shunt, but only one in the treatment group (p = 0.03). Treatment with indomethacin prolonged bleeding time, raised serum creatinine concentrations, and was associated with gastrointestinal haemorrhage in seven infants. Five of these had a serum indomethacin concentration greater than 1.0 microgram/ml. There was a significant reduction of the stable metabolite of prostacyclin, 6-ketoprostaglandin F1 alpha, commencing six hours after treatment and lasting for four days. There was no significant difference in the incidence of intraventricular haemorrhage, days of treatment with oxygen or ventilation, or mortality between the two groups.     

The effect of birth asphyxia on plasma free amino acids in preterm newborn infants

The postnatal plasma amino acid pattern was compared in 16 asphyxiated and 13 non-asphyxiated preterm newborn infants. The lactic acidosis induced by asphyxia was associated with a marked rise in the total amino acid content of the plasma. Among the 17 individual amino acids determined the concentrations of alanine, proline, taurine, glutamate, valine, methionine and lysine were significantly elevated. The accumulation of alanine was particulary marked and its concentration showed a significant linear correlation with that of lactate (p less 0.001). A similar relationship was observed between other potentially glucogenic amino acids and lactate. It is suggested that an impaired gluconeogenesis may be responsible for the accumulation of glucogenic amino acids. The response of the plasma aminogram to asphyxia resembles that associated with hypoglycaemia in the small-for-gestational-age infant, where a delay in the maturation of key gluconeogenic enzymes seems to account for the reduced hepatic disposal of glucose precursors.     

Effect of phototherapy on nitrogen and electrolyte levels and water balance in jaundiced preterm infants

Twenty-four-hour metabolic balance studies were performed in ten jaundiced preterm infants, five light-treated (phototherapy) and five controls. Each of the light-treated infants was studied twice, once during phototherapy (period I) and once 48 hours after phototherapy (period II). Control infants were similarly studied during the corresponding days. Compared to period II and control infants, during period I the light-treated infants had less weight gain. Intestinal transit time was decreased by 50%. Fecal excretion of nitrogen, sodium, and potassium was increased. Stool water loss was increased twofold to threefold with a decrease in water balance. Unmeasured water loss was increased. These studies underscore the need for careful attention to fluid and caloric supplementation during phototherapy.     

Erythromycin fails to improve feeding outcome in feeding-intolerant preterm infants

OBJECTIVE: Approximately half of extremely low birth weight infants have feeding intolerance, which delays their achievement of full enteral feedings. Erythromycin, a motilin receptor agonist, triggers migrating motor complexes and accelerates gastric emptying in adults with feeding intolerance. Few studies have assessed the efficacy of this drug in preterm infants with established feeding intolerance. This study was designed to assess the efficacy of erythromycin in feeding-intolerant infants, as measured by gastric emptying, maturation of gastrointestinal motor patterns, and time to achieve full enteral feedings. METHODS: Subjects were 27 preterm infants who were admitted to the neonatal intensive care unit and who did not achieve full enteral feeding volumes (150 mL/kg/day) within 8 days of the initiation of feedings. In a controlled, randomized, double-blinded clinical trial, infants received intragastric erythromycin or placebo for 8 days without crossover. At study entry, the authors recorded motor activity in the antrum and the duodenum during fasting, in response to intragastric erythromycin (1.5 mg/kg) or placebo, and in response to feeding. Gastric emptying at 20 minutes and transit time from duodenum to anus were determined. Each infant then received erythromycin or placebo for 8 days, and feeding characteristics were prospectively tracked. RESULTS: Gastric emptying and characteristics of antroduodenal motor contractions were similar in the two groups, as were the transit times from duodenum to anus. Feeding outcomes were comparable in the two groups. CONCLUSION: Intragastric erythromycin does not improve feeding tolerance in preterm infants with established feeding intolerance because it fails to improve gastrointestinal function in the short or long term.     

Early aggressive nutrition in preterm infants

Increasingly, neonatologists are realizing that current feeding practices for preterm infants are insufficient to produce reasonable rates of growth, and earlier and larger quantities of both parenteral and enteral feeding should be provided to these infants. Unfortunately, there is very little outcome data to recommend any particular nutritional strategy to achieve better growth. Instead, the rationale for feeding regimens in many nurseries has been quite variably extrapolated from animal data and human studies conducted in gestationally more mature and/or stable neonates. Additionally, there are no well-controlled, prospective studies that validate any nutritional regimen for the very preterm and or sick, unstable neonate. The goal of this review is to present available data to help define the risks and benefits of early parenteral and enteral nutrition, particularly in very preterm neonates, concluding with a more aggressive approach to feeding these infants than has been customary practice.