Parenteral multivitamin supplementation induces both oxidant and antioxidant responses in the liver of newborn guinea pigs

BACKGROUND: The multivitamin solution is a major component of photo-induced generation of peroxides in parenteral nutrition. The aim of this study was to determine whether the parenteral multivitamin preparation induces in the liver a peroxide-induced oxidant challenge or an antioxidant protection associated with the antiradical components of the solution. METHODS: Newborn guinea pigs were infused with dextrose supplemented with peroxides (250 micromol/L H2O2 or 350 micromol/L tert-butylhydroperoxide) or with a multivitamin preparation (MVP, 1% vol/vol). After 4 days, total glutathione and a free radical-sensitive eicosanoid marker (prostaglandin I2 [PGI2]/total prostaglandins) were measured in livers. RESULTS: There was a significant decrease in the PGI2/total prostaglandin ratio (mean +/- SEM) [dextrose: 0.068 +/- 0.007 vs. (dextrose + H2O2: 0.048 +/- 0.001, dextrose + TBH: 0.043 +/- 0.001)] and glutathione concentrations decreased [dextrose: 55 +/- 7 vs. (dextrose + H2O2: 37 +/- 7, dextrose + TBH: 18 +/- 7 nmol/mg protein)] after infusion of peroxides. Despite the peroxide load in the multivitamin solution, it did not alter the measured variables as prostanoid ratio remained at control concentrations (dextrose: 0.066 +/- 0.008 vs. dextrose + MVP: 0.065 +/- 0.006), as did glutathione levels (dextrose: 52 +/- 6 vs. dextrose + MVP: 45 +/- 7 nmol/mg prot). CONCLUSION: In the liver of guinea pig pups, infused peroxides cause oxidation of membrane-derived prostanoids. The decrease in glutathione in response to administration of peroxides suggests consumption rather than a response to a free radical attack. Despite the oxidant load associated with peroxides generated in MVP, the multivitamin preparation protected membranes as the prostanoid ratio, and glutathione levels remained at control levels.     

Photooxidation of parenteral multivitamins induces hepatic steatosis in a neonatal guinea pig model of intravenous nutrition

Photooxidation of multivitamin solutions results in the generation of peroxides. Because peroxides are associated with hepatic steatosis and fibrosis as well as cholestasis, we questioned whether multivitamins are implicated in hepatic complications of parenteral nutrition. Guinea pig pups were assigned to groups receiving intravenously either total parenteral nutrition, photo-protected or not, or a control solution (5% dextrose + 0.45% NaCl) supplemented with either a) multivitamins; b) photo-protected multivitamins; c) multivitamins without riboflavin; or d) peroxides (H(2)O(2), tert-butylhydroperoxide). After 4 d, liver was sampled for histology and isoprostane-F(2alpha) levels, a marker of radical attack. Multivitamins as well as total parenteral nutrition were associated with steatosis (scored 0-4), the severity of which was reduced (p < 0.05) by photo protection. Although H(2)O(2) is the major peroxide contaminating multivitamins, it did not induce steatosis scores different than the controls. Compared with controls, hepatic isoprostane-F(2alpha) content increased in animals infused with H(2)O(2) (p < 0.05), but not in those infused with Multi-12 pediatric multivitamins or total parenteral nutrition. Results suggest that peroxides and/or free radicals are not mediators of the induction of steatosis observed with infusion of photo-exposed multivitamins, as there was no correspondence between histologic findings and hepatic levels of isoprostanes. It is suspected that a component of the multivitamin solution becomes hepato-toxic after photo-exposure, as indicated by the protective effect observed when withdrawing riboflavin. Photo-oxidation of multivitamins might be the common link between reports involving amino acids, lipids, and light exposure in the ethiology of hepatic complications of parenteral nutrition.     

Total parenteral nutrition-associated cholestasis: acute studies in infant and adult rabbits

To assess the basis of cholestasis associated with total parenteral nutrition (TPN), we studied the short-term effect of the component solutions on bile flow and bile salt secretion in infant and adult rabbits. Groups of four to six adult and infant rabbits received intravenously 154 mM NaCl (control), 2.5% amino acid, 10% glucose, or 10% fat emulsion alone or in combination. Bile was collected directly from the common bile duct for 3 h. Solutions containing both amino acids and glucose significantly (p less than 0.05) reduced bile flow and bile salt secretion in both age groups. Glucose alone also decreased bile flow and bile salt secretion, whereas amino acids as the sole infusate significantly (p less than 0.05) decreased bile flow only. The suppressive effect of the amino acid-glucose solutions on bile flow was more pronounced in infants than in adults. Fat emulsion alone had no effect on bile formation. Our findings demonstrate that short-term intravenous administration of nutrient solutions containing amino acids and glucose reduces bile flow and bile salt secretion, suggesting that these components are responsible for TPN-associated cholestasis.     

Cholestasis in total parenteral nutrition--a review

Intrahepatic cholestasis is a frequent, however unresolved complication of total parenteral nutrition in infancy. A frequency of 10-50% is reported. The concentration of serum bile acids seems to be a sensitive indicator for a beginning cholestasis. As typical histological alterations of the liver are considered: inflammatory portal reaction, fibrosis and proliferation of bile ducts. As important components of the obviously multifactorial etiology are considered: lacking oral alimentation, fetal bile acid synthetic pathways, amino acid toxicity, hypoalbuminemia, sepsis and substrate excess.     

The effects of acetylsalicylic acid, interferon-alpha, and vitamin E on prevention of parenteral nutrition-associated cholestasis: an experimental study

BACKGROUND: Cholestasis is one of the major complications of parenteral nutrition. The purpose of this experimental study was to detect the effects of acetylsalicylic acid (ASA), vitamin E (Vit E), and interferon-alpha (IFN-alpha) on prevention of parenteral nutrition-associated cholestasis. METHODS: Ten experimental groups, each consisting of 10 4-week-old Wistar albino rats, were formed: control 10- and 20-day groups (C10 and C20), parenteral nutrition-only 10- and 20-day groups (T10 and T20), ASA-supplemented parenteral nutrition 10- and 20-day groups (TA10 and TA20), Vit E-supplemented parenteral nutrition 10- and 20-day groups (TE10 and TE20), and IFN-alpha-supplemented 10- and 20-day groups (TF10 and TF20). Acetylsalicylic acid, Vit E, and IFN-alpha were administered in the parenteral nutrition solution through an intraperitoneal route. At the end of the study, serum total bile acids, serum aspartate and alanine aminotransferases, and alkaline phosphatase were measured biochemically. In addition, the histopathologic findings of cholestasis were evaluated by using a morphologic portal inflammation index. RESULTS: Although the difference in the serum levels of transferases and alkaline phosphatase was not significant among all groups (p > 0.05), it was significant in total bile acid levels (p < 0.05). There was also a significant correlation between the histopathologic changes of the liver and serum total bile acid concentrations (p < 0.05). Portal inflammation in varying degrees was seen in all experimental groups, but not in the control groups. Serum total bile acid concentrations in parenteral nutrition groups receiving ASA were significantly lower than those in the parenteral nutrition-only group (p < 0.01). Although Vit E-supplemented parenteral nutrition was effective in preventing the development of cholestasis in the 10-day group (p < 0.05), it was not effective in the 20-day group when compared with incidence of cholestasis in the parenteral nutrition-only group (p > 0.05). Conversely, IFN-alpha-supplemented parenteral nutrition had no effect on cholestasis in the 10-day group (p > 0.05) but lowered cholestasis in the 20-day group when compared with incidence the parenteral nutrition-only group (p < 0.05). CONCLUSION: Our results indicate that acetylsalicylic acid may be beneficial in preventing, and (alpha-interferon in treating, parenteral nutrition-associated cholestasis.     

Aluminum contamination of parenteral nutrition and aluminum loading in children on long-term parenteral nutrition

BACKGROUND: Children who are receiving parenteral nutrition are at risk of aluminum overload, which may contribute to such side effects as osteopenic bone disease. The aim of the present study is to determine the aluminum contamination of parenteral nutrition solutions and their components, and to assess the aluminum status of children on long-term parenteral nutrition. METHODS: Aluminum concentrations were determined by graphite furnace absorption spectroscopy in components and in final parenteral nutrition solutions. The urinary aluminum excretion and plasma aluminum concentration were determined in 10 children on long-term parenteral nutrition. RESULTS: The mean aluminum concentration in the administered parenteral nutrition solutions was 1.6 +/- 0.9 micromol x l(-1)(mean +/- standard deviation (SD)). The resulting mean aluminum daily intake of the 10 patients was 0.08 +/- 0.03 micromol x kg(-1) x day(-1). CONCLUSIONS: Compared to two previous studies performed in 1990 and in 1995 in our hospital, the aluminum contamination of parenteral nutrition solutions and the daily aluminum intake of the children seemed to decrease. However, the plasma aluminum concentration and daily urinary aluminum excretion of the children still remain above normal standards. The children had no clinical symptoms of bone disease but aluminum accumulation in tissue can not be excluded. To prevent this iatrogenic toxicity, the aluminum contamination of parenteral nutrition should be assessed regularly.     

Homocysteine prevents total parenteral nutrition (TPN)-induced cholestasis without changes in hepatic oxidative stress in the rat

BACKGROUND: The role of oxidative stress in total parenteral nutrition (TPN)-associated cholestasis with liver glutathione depletion was recently shown. The aims of this study were to test the appearance of cholestasis and oxidative stress during TPN, and the hypothesis that reducing oxidative stress with a precursor of glutathione (GSH), homocysteine, would restore bile flow. METHODS: Three groups of rats (weight, 179-278 g) were studied: 1) D/aa group received dextrose and amino acids (3.4 g/d); 2) D/aa/L group received the same amount of amino acids, and lipids were added on an equicaloric basis (50 kcal/d) with a lowered amount of dextrose; and 3) a control group, which received dextrose perfusion and had free access to chow. A subgroup of D/aa/L rats (n = 6) received a TPN solution containing homocysteine. After 5 days of TPN, bile was collected during 2 hours. In liver homogenates, GSH, thiobarbituric acid reactive substances (TBARS), and carbonyl content of proteins (Prot-CO) were measured to test the level of oxidative stress and hepatic lipid and protein oxidation. RESULTS: After TPN, bile flow was significantly lower in the D/aa group than in the control group. Addition of lipids further decreased bile flow. Addition of homocysteine to TPN with lipids significantly increased bile flow. Aspartate aminotransferase increased significantly in both TPN groups compared with the control group. gamma-Glutamyl transpeptidase was not different among TPN groups. An increased hepatic lipid oxidation was demonstrated by TBARS level in both TPN groups when compared with the control group. However, the liver GSH contents were not different. Protein oxidation was also significantly increased by TPN. The addition of homocysteine to TPN solution increased bile flow without liver injury or changes of lipid and protein oxidation. DISCUSSION: This study shows that TPN administered to rats induces a decrease of bile flow and an oxidative stress but that the two changes are not directly correlated. Addition of lipids further impairs bile flow but does not increase the occurrence of liver injury. Consequently, it seems more likely that TPN primarily induces a cholestatic effect that in turn induces an oxidative stress rather than inducing an oxidative stress that leads to cholestasis. However, an association of both mechanisms is not totally excluded.     

Intravenous fish oil emulsion attenuates total parenteral nutrition-induced cholestasis in newborn piglets

Total parenteral nutrition (TPN) causes intrahepatic cholestasis and membrane phospholipid changes. Fatty acid (FA) composition of bile and hepatocyte phospholipid is influenced by dietary FA composition. We hypothesized that altering FA composition of i.v. lipid emulsions modifies 1) severity of TPN-induced cholestasis; 2) hepatocyte membrane composition and function; 3) bile flow and composition. Newborn piglets received either sow's milk, TPN with i.v. soybean oil or TPN with i.v. fish oil (FO). After 3 wk, basal and stimulated bile flow were measured after bolus injections of 20, 50, and 100 micromol/kg of taurocholate (TCA). Bile was analyzed for bile acids, cholesterol, phospholipids, and phospholipid-FA. Sinusoidal and canalicular membrane PL-FA, fluidity, and Na+/K+-ATPase were measured. Although the soybean oil-fed animals developed cholestasis, the FO and milk group had similar liver and serum bilirubin. Basal and stimulated bile flow rates were impaired in the soybean oil but not in the FO group. Hepatocyte membrane FA composition reflected dietary FA. Changes in sinusoidal and canalicular membrane fluidity and sinusoidal Na+/K+-ATPase activity did not explain the effect of FO on TPN-induced cholestasis. Intravenous FO reduces TPN-induced cholestasis by unknown mechanisms.     

Preventing parenteral nutrition liver disease

Parenteral nutrition liver disease (PNLD) develops in 40-60% of infants who require long-term PN for intestinal failure. The clinical spectrum includes hepatic steatosis, cholestasis, cholelithiasis, and hepatic fibrosis. Progression to biliary cirrhosis and the development of portal hypertension and liver failure occurs in a minority who require combined liver and intestinal transplantation.The pathogenesis is multifactorial and is related to prematurity, low birth weight, duration of PN, short bowel syndrome requiring multiple laparotomies and recurrent sepsis. Other important mechanisms include lack of enteral feeding which leads to reduced gut hormone secretion, reduction of bile flow and biliary stasis which leads to the development of cholestasis, biliary sludge and gallstones, which exacerbate hepatic dysfunction, especially in premature neonates with immature hepatic function.The use of lipid emulsions, particularly soy bean emulsions have been associated with hepatic cholestasis in children, although there are little data now to support toxicity from other PN components.Management strategies for the prevention of parenteral nutrition liver disease include consideration of early enteral feeding, a multidisciplinary approach to the management of parenteral nutrition with a specialized nutritional care team and aseptic catheter techniques to reduce sepsis. The use of specialized lipid emulsions such as fish oil emulsions and or SMOF (Soy bean/Medium Chain Triglyceride/Olive Oil/Fish oil) improves established cholestasis and may prevent the onset.Oral administration of ursodeoxycholic acid may improve bile flow and reduce gall bladder stasis, although there is little data to suggest that prophylactic use prevents the onset of PNLD.Survival following either isolated small bowel or combined liver and small bowel transplantation is approximately 50% at 5 years making this an acceptable therapeutic option in children with irreversible liver and intestinal failure.     

Total parenteral nutrition cholestasis: a cause of mechanical biliary obstruction

In a newborn baby with Hirshsprung's disease obstructive jaundice developed following prolonged parenteral nutrition. At laparotomy, thick inspissated bile was flushed from the biliary tree and prompt resolution of the jaundice followed. To our knowledge, this is the first reported case in which inspissated bile appeared to be a complication of total parenteral nutrition. Mechanical obstruction must be recognized as an extreme in the spectrum of total parenteral nutrition cholestasis.     

Hepatobiliary abnormalities and parenteral nutrition

Hepatobiliary dysfunctions (TPN-HBD) occur during parenteral nutrition. In older children these are usually reversible whereas in newborns and infants these hepatobiliary abnormalities play a significant role in the morbidity. Cholestasis is a commonly occurring TPN-HBD. It correlates directly with the decreasing gestational age, low birth weight and increasing duration of TPN therapy. The pathogenesis of cholestasis of TPN is multifactorial and predisposed by necrotising enterocolitis, sepsis, cardiac failure, shock, and hypotension. Diagnosis is made with exclusion of other causes of direct hyperbilirubinemia. Most TPN-HBD appear within 4 weeks of starting of TPN but severe complications manifest usually after the 16th week. Histologically there is intralobular cholestasis. In few cases there may be severe portal fibrosis followed by development of micronodular biliary cirrhosis. Enteral starvation, defective bile acid carriers, hypercaloric TPN are the major factors responsible for TPN-HBD, including cholestasis. Biliary complications of TPN-HBD are acalculous, cholecystitis, and cholelithiasis. Bile stasis is a major pathological factor for these. If the calories are provided only by glucose or glucose-containing electrolyte solutions it may lead to cholestasis and other TPN-HBD. Even small oral elimentation (continuous or bollous) during TPN, prevent TPN-HBD. Choleretic agents have been useful in the prevention and management of cholestasis and other parenteral nutrition induced hepatobiliary abnormalities.     

Effect of taurine supplementation on hepatic function during short-term parenteral nutrition in the premature infant

To evaluate the potential role of taurine deficiency in the pathogenesis of parenteral nutrition-induced cholestasis, 20 premature (less than 34 weeks AGA) infants were randomized to receive parenteral nutrition with and without taurine (10.8 mg/kg/day) during the first 10 days of life. Birth weight, gestational age, and protein and caloric intake were similar in both groups. Plasma taurine levels and hepatic function were assessed before the study began (3 +/- 1 days of age), at 5 +/- 1 days of age, and at 9 +/- 1 days of age. Although plasma taurine levels were significantly greater at 5 +/- 1 and 9 +/- 1 days of age (p = 0.009) in the group receiving supplementation, no differential effect on hepatocellular function could be detected during this short period of time. A decrease in plasma ammonia (p = 0.001), alanine aminotransferase (ALT) (p = 0.036), gamma-glutamyltranspeptidase (GGTP) (p = 0.05), 5'-nucleotidase (5'N) (p = 0.001), and bile salt concentrations was noted in both groups, indicating the rapid maturation of hepatic function even in the presence of parenteral nutrition during the first 10 days of life.     

Increased urinary peroxides in newborn infants receiving parenteral nutrition exposed to light

OBJECTIVES: To determine whether peroxide loads infused with total parenteral nutrition (TPN) are fully quenched by premature infants. STUDY DESIGN: After baseline urine peroxide levels were established, the effect of various parenteral regimens was correlated with urinary peroxide levels in 64 newborn infants 相似文献   

Intravenous alimentation and insensible water loss in low-birth-weight infants.

Insensible water loss (IWL) was measured in six premature infants, between 4 and 21 days of age, by continuous weight monitoring on an electronic balance inside an incubator. Multiple measurements of IWL were made during the sequential infusion of 10% dextrose in 0.225% NaCl, 10% dextrose-amino acid solution, or 10% dextrose-amino acid and a commercial intravenous fat emulsion. Each solution was administered for three hours by constant infusion through a scalp vein needle. The order of the infusion was random and a 30- to 60-minute infusion with 5% dextrose water was given between each solution. During the infusion of 10% dextrose in 0.225% NaCl and 10% dextrose + amino acid solution, IWL was 1.0 +/- 0.8 gm/kg/hr and 1.1 +/- 0.8 gm/kg/hr, respectively. In contrast, IWL increased significantly to 1.6 +/- 0.7 gm/kg/hr when additional calories were given using the 10% dextrose-amino acid with the intravenous fat emulsion (P less than .005). There was a positive correlation between calorie intake and IWL. These data suggest that parenteral nutrition solutions with intravenous fat emulsion are rapidly metabolized and the increase in IWL is probably secondary to an increase in thermogenesis.     

早产儿胃肠外营养相关性胆汁淤积症临床研究

目的 探讨生后早期使用静脉营养的早产儿胆汁淤积症的临床特点,分析胃肠外营养相关性胆汁淤积症(parenteral nutrition associated cholestasis,PNAC)的相关因素及防治措施.方法 回顾性分析2011年1月至2016年4月出生并在盛京医院住院治疗的早产儿,生后均早期使用静脉营养2周,后出现胆汁淤积,共89例,分为两组,PNAC组即符合PNAC诊断(未发现其他导致胆汁淤积原因)41例,多病因组(除胃肠外营养因素还有其他病因)48例.通过病例对照研究分析其临床特点.结果 早产儿胆汁淤积症的男女比例为2.18:1,平均胎龄(31.05 ±2.15)周,平均出生体重(1360.55±421.14)g,静脉营养平均使用时间为(26.22±9.78)d.PNAC组根据丙氨酸氨基转移酶是否升高又分为肝炎组与非肝炎组,两组在胎龄、静脉营养开始时间、生后黄疸出现时间、开奶时间、氨基酸起始剂量及脂肪乳最大剂量方面的差异均有统计学意义,(P＜0.05);根据胃肠外营养时间分为长期组(≥20d)与短期组(＜20 d),长期组的谷丙转氨酶、谷草转氨酶、总胆红素、直接胆红素及胆汁酸水平均高于短期组,但P均≥0.05.多病因组患儿多合并感染,依次为细菌感染(75.0％)、真菌感染(20.83％)、巨细胞病毒感染(8.33％)和梅毒感染(2.08％)等.PNAC组和多病因组其他并发疾病的发生率差异无统计学意义.在预后方面,两组患儿经过保肝治疗后肝功能均较前明显好转,PNAC组的各项指标较多病因组降低更为显著(P＜0.05).结论 PNAC是早产儿胆汁淤积症发生的主要因素,PNAC早产儿肝损伤程度与胃肠外营养开始时间、使用时间、肠内喂养时间、氨基酸起始剂量及脂肪乳最大剂量有关.经保肝对症治疗后肝功能可以明显恢复,且效果优于多病因所致的胆汁淤积症.     

胃肠道外营养对早产儿肝胆功能的影响

目的：胃肠道外营养是提高早产儿成活率的主要手段之一,但由于早产儿肝肾功能、脂质清除等不成熟,胃肠道外营养的运用还存在某些争议的问题,胃肠道外营养时早产儿肝胆功能的损害已日益受到重视。该研究探讨胃肠道外营养对早产儿肝胆功能的影响。方法：对75例实行胃肠道外营养的早产儿及49例未实行胃肠道外营养的早产儿,各营养成分输入后的监测结果进行统计分析。结果：治疗后研究组及对照组谷草转氨酶、总胆红素、未结合胆红素均比治疗前明显下降,统计学差异有非常显著性(P<0.01);而谷丙转氨酶、结合胆红素则在治疗前后变化不明显,差异无显著性(P>0.05);治疗后研究组总胆汁酸(TBA)水平升高,差异有非常显著性(P<0.01),与胃肠道外营养持续时间呈正相关,与胎龄呈负相关;对照组治疗后总胆汁酸变化不明显,差别无统计学意义(P>0.05)。结论：早产儿胃肠道外营养时血清总胆汁酸(TBA)水平升高,应警惕胆汁淤积。     

Biliary motility: postnatal changes in guinea pigs

Intravital microscopy, a new in vivo technique, documented age-dependent changes in choledochoduodenal junction motility in male guinea pigs. In the guinea pig, the choledochoduodenal junction served as a pump that actively emptied its luminal contents into the duodenum. In the neonates (less than or equal to 1 wk old), this choledochoduodenal junction pump was not fully developed. Unlike the older guinea pigs, some neonates had an incompetent sphincter ductus choledochi (SDC) allowing retrograde flow of bile during ampullary contractions. While fasting, neonates had decreased frequency of SDC (1.2 +/- 0.4 contractions/min) and ampullary (0.1 +/- 0.1 contractions/min) contractions as compared to juveniles (4-6 wk old) (SDC = 6.4 +/- 1.0; ampulla = 1.2 +/- 0.2 contractions/min) and adults (greater than 1 yr old) (SDC = 6.7 +/- 1.6; 0.8 +/- 0.2 contractions/min). Following a meal (Ensure), unlike older guinea pigs, the neonate did not have a significant increased duration and decreased frequency of SDC contractions. Altered neonatal SDC motility correlated with an incompletely developed SDC including decreased muscle mass and mucosal thickness. By 4 wk of age, choledochoduodenal junction motility was similar to that of the adult. These developmental alterations in junctional motility and structure may affect the flow of bile into the duodenum contributing to physiologic cholestasis and decreased intraduodenal bile acids seen in neonates.     

Parenteral nutrition-associated cholestasis--what do we know, what can we do?

In the early days of parenteral nutrition of children liver disease resulting in steatosis and cholestasis was assumed to be an inevitable complication of the procedure. Since then, the management of parenteral nutrition has improved so much that nowadays adolescents have a fair chance of surviving more than 15 to 20 years without severe liver disease. Nevertheless, we still see cases of parenteral nutrition-associated cholestasis (PNAC) due to various conditions such as recurrent infections, inflammatory response, inappropriate composition of the nutrient mixture, contaminants of the nutrient solution, and toxic substances from infusion bags and tubes. Recent research indicates that the administration of ursodesoxycholic acid and cysteine can prevent or even improve the cholestasis. A reversal of PNAC has been documented in an adolescent after small bowel transplantation from Japan. There is ample opportunity for prevention of PNAC with respect to the various pathophysiologic aspects: prevention, early detection, and management of infections, avoiding glucose overloads, cyclic infusion of nutrients, light protection of the solution, choice of paediatric amino acid solutions, and most important, oral or enteral feeding to support the bile flow by stimulating the cholecystokinine release.     

Amino acid mixture designed to maintain normal plasma amino acid patterns in infants and children requiring parenteral nutrition

A mixture of amino acids designed to maintain normal plasma amino acid concentrations of infants and children requiring parenteral nutrition was evaluated in 40 infants and children receiving only parenteral nutrients (2.39 +/- 0.26 g/kg/d of amino acids and 110.3 +/- 10.4 kcal/kg/d) for five to 21 days. The children ranged in weight from 2.0 to 12.6 kg (median weight, 3.83 kg; fifth to 95th percentile, 2.06 to 11.1 kg) and in age from 1 week to 43.6 months (median age, 2.7 months; fifth to 95th percentile, 0.2 to 25.3 months). Mean weight gain was 11.0 +/- 5.0 g/kg/d; mean nitrogen balance was 242 +/- 70 mg/kg/d. Plasma concentrations of all amino acids except tyrosine were within the normal range (ie, within the 95% confidence limits of the two-hour postprandial plasma concentrations observed in 30-day-old, healthy, normally growing, breast-fed, term infants) throughout the period of study. Mean prestudy and poststudy serum total protein, albumin, and transthyretin (prealbumin) concentrations were not significantly different. However, plasma transthyretin concentration increased in all children with low prestudy concentrations. Mean poststudy serum total bilirubin concentration of the total population was not different from the mean prestudy concentration. This was true also for the 31 children who received the parenteral amino acid mixture for more than ten days. In contrast to the expected 30% to 50% incidence of cholestasis, only one of these 31 experienced an unexplained increase in serum total bilirubin concentration during study, suggesting that normalizing plasma amino acid concentrations and/or providing taurine during parenteral nutrition may decrease the incidence of cholestasis associated with this therapy.     

The changing pattern of diagnosis of infantile cholestasis

OBJECTIVE: Cholestatic liver disease in infancy is caused by a wide range of conditions. This study reviews the pattern of diagnosis of infants with cholestasis presenting to a tertiary referral paediatric hospital in Sydney, Australia, during a 12-year period (1985-96). METHODOLOGY: Infants aged less than 6 months with cholestasis were identified retrospectively from hospital records and data retrieved from the medical records. RESULTS: There were 205 infants identified as having cholestatic liver disease. The aetiology of the cholestasis was idiopathic in 25%, metabolic/genetic in 23%, and due to obstruction in 20%, parenteral nutrition in 20%, infection in 9% and bile duct hypoplasia in 3%. CONCLUSIONS: This study highlights the changing patterns of diagnosis of cholestatic liver disease in infants at a tertiary paediatric facility, demonstrating that up to 50% of cases are now due to genetic/metabolic diseases or parenteral nutrition, and a high proportion are due to idiopathic disease.