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The field of parenteral nutrition continues to evolve along two major paths: prevention of complications and refining of nutritional needs. Parenteral nutrition-associated liver disease remains a vexing problem. No single factor is to blame; rather, it requires a number of "hits." In the infant, the liver disease primarily appears to be related to prematurity of bile flow and production, infection, lack of enteral feedings, and most recently appreciated, perhaps free radicals. We are able to meet the nutritional needs of our patients, but our knowledge of actual nutritional requirements remains incomplete. Future studies need to define better appropriate intakes and to rigorously test the utility of proposed nutrients such as glutamine.
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PMID:New developments in total parenteral nutrition for children. 1095 38

Parenteral nutrition is a life-saving therapy for patients with intestinal failure. It may be associated with transient elevations of liver enzyme concentrations, which return to normal after parenteral nutrition is discontinued. Prolonged parenteral nutrition is associated with complications affecting the hepatobiliary system, such as cholelithiasis, cholestasis, and steatosis. The most common of these is parenteral nutrition-associated cholestasis (PNAC), which may occur in children and may progress to liver failure. The pathophysiology of PNAC is poorly understood, and the etiology is multifactorial. Risk factors include prematurity, long duration of parenteral nutrition, sepsis, lack of bowel motility, and short bowel syndrome. Possible etiologies include excessive caloric administration, parenteral nutrition components, and nutritional deficiencies. Several measures can be undertaken to prevent PNAC, such as avoiding overfeeding, providing a balanced source of energy, weaning parenteral nutrition, starting enteral feeding, and avoiding sepsis.
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PMID:Parenteral nutrition-associated liver complications in children. 1183 58

Various factors can influence the metabolism of surgical neonates. These include prematurity, operative stress, critical illness, and sepsis. The nutritional management of surgical infants with congenital or acquired intestinal abnormalities has improved after the introduction of parenteral nutrition. This article is focused on the energy and protein metabolism of surgical neonates with particular reference to the metabolic response to operative trauma and sepsis. The metabolic utilization of intravenous nutrients also is discussed. The metabolic response to operative trauma is different between neonates and adults. Infants have high rates of protein turnover and are avid retainers of nitrogen. Energy expenditure increases only transiently (4 to 6 hours) after major surgery in neonates. Protein turnover and catabolism seems not to be affected by major operative procedures in neonates. In neonates on parenteral nutrition, carbohydrate and fat have an equivalent effect on protein metabolism. The main determinants of fat utilization are carbohydrate intake and resting energy expenditure. Parenteral nutrition in surgical neonates is associated with increased production of oxygen-free radicals. This seems to be related to intravenous fat administration. Promoting fat utilization by reducing the carbohydrate to fat ratio in the intravenous diet reduces free radical activity to a similar extent as fat exclusion. Glutamine appears to be safe for use in neonates and infants and is "conditionally essential" in very-low birth weight infants and in septic neonates. Enteral glutamine supplementation in very-low birth weight infants reduces the risk of sepsis. The metabolism of surgical neonates is affected by operative trauma, critical illness, and sepsis. Nutritional support in surgical neonates has a profound impact on outcome. Exogenous glutamine can modulate immune, metabolic, and inflammatory responses. Further investigations are needed to clarify the clinical benefit of parenteral or enteral glutamine administration in surgical neonates.
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PMID:Metabolism and nutritional support in the surgical neonate. 1203 42

The study aimed at obtaining insights into the processes underlying infant deaths to help identify preventive interventions which may bring down infant mortality rates further. Verbal autopsies were performed on 162 deaths of liveborn infants that occurred in a birth cohort in two urban slums of Delhi, India, between February 1995 and August 1996. A structured verbal autopsy form was used for ascertaining the cause of death. The narratives of caretakers on seeking of care and treatment received for illness were reviewed to identify the actions and behaviours that might have contributed to death. Seeking of care was less common (57%) for illnesses that led to death in the first week of life than at later ages. The first-week deaths commonly (61%) occurred within 24 hours of recognition of illness which might have been too a short time for effective interventions by care providers. Only six of 45 neonates who had features of sepsis, pneumonia or meningitis, major congenital malformations, birth asphyxia, or prematurity were advised by primary care providers for hospitalization. Similarly, only 25 (41%) of 61 older infants who had severe malnutrition and sepsis or meningitis, diarrhoea or pneumonia, or other illnesses were referred to hospital. Parenteral antibiotics were prescribed less often than warranted. Only two of 16 neonates with serious bacterial infections and eight of 19 postneonates with features of sepsis or meningitis received parenteral antibiotics. Inappropriate healthcare practices were common among the practitioners of modern and indigenous systems of medicine and registered medical practitioners. Forty percent of the neonates and a little over half of the older infants, advised for hospitalization, were taken to hospital. Fifteen percent of the infants taken to hospital were refused admission. Of 21 hospitalized infants discharged alive, five (23%) died within 48 hours and 13 (62%) within a week of returning home. A major effort is required to improve skills of healthcare providers of the biomedical and indigenous systems of medicine in caring for neonates and infants. Development of home-based treatment regimens for young infants and objective criteria for their hospitalization and discharge should receive a high priority.
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PMID:Pathways to infant mortality in urban slums of Delhi, India: implications for improving the quality of community- and hospital-based programmes. 1218 95

Parenteral multivitamins (MVP) are linked to the generation of peroxides, which cause oxidant injury in lungs associated with alveolar remodelling linked to lung disease of prematurity. This study was to investigate the relationship between alveolar development and lung oxidant-antioxidant status as modulated by the mode of administration of multivitamins with total parenteral nutrition (TPN). Four groups of guinea pig pups received parenteral nutrition differing by 1) mode of MVP admixture: with amino acid solution (AA-MVP) or lipid emulsion (LIP-MVP); 2) light exposure: TPN exposed (LE) or shielded from light (LP). After 2 or 4 days of TPN, vitamins C and E, 8-isoprostaneF2alpha and alveolarization index were determined in lungs and GSSG/GSH in lungs and blood. Exposure to light and the mode of MVP admixture did not influence vitamin E and isoprostane levels. Blood glutathione redox potential was more oxidized in LE and LIP-MVP groups after 4-day infusions, whereas lung redox potential was more reduced in LE groups. LP and LIP-MVP had a beneficial effect, with higher number of alveoli. Globally, results indicate that in this model, alveolarization and modifications in lung redox potential are two independent events induced by light exposed TPN.
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PMID:Influence of lung oxidant and antioxidant status on alveolarization: role of light-exposed total parenteral nutrition. 1847 54

Bronchopulmonary dysplasia (BPD) is a chronic lung disease of infancy which is associated with prematurity and early lung injury resulting from mechanical ventilation. Oxygen toxicity, barotrauma, and volutrauma play key roles in its pathogenesis. Parenteral administration of Vitamin A to the newborn is the current recommended preventive therapy for BPD. Vitamin A has been found to upregulate genes necessary for fetal lung growth and increase surfactant production in animal models. Supplementation of Vitamin A in late pregnancy increases the cord blood vitamin A levels proportionately. Hence, we hypothesize that Vitamin A supplementation during late pregnancy can decrease the incidence of BPD in newborns. This can be an effective adjunct to postnatal preventive therapy. Vitamin A supplementation in late pregnancy carries no risk of teratogenicity unlike in early pregnancy. Moreover, vitamin A deficiency in pregnancy is associated with depressed immune function leading on to increased infectious morbidity and can cause intrauterine growth retardation, low birth weight and anemia in newborns. Combining antenatal Vitamin A supplementation to the mother with postnatal supplementation to the newborn can effectively prevent BPD better than the traditional postnatal preventive therapy alone. It will also treat the highly prevalent vitamin A deficiency in pregnant mothers and newborns of the developing world.
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PMID:Vitamin A supplementation in late pregnancy can decrease the incidence of bronchopulmonary dysplasia in newborns. 2029 8

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.
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PMID:Preventing parenteral nutrition liver disease. 2092 19

Parenteral nutrition (PN) is necessary for infants unable to receive adequate calories enterally due to prematurity, decreased bowel length, or functional intestinal disorders. While PN can be life saving, its use is associated with significant risks of sepsis from catheter-associated infections and progressive liver dysfunction from prolonged use. The preterm infant population is at highest risk for these complications due to the presence of multiple comorbidities and immaturity of the biliary system. Strong data has implicated parenteral lipids in the multifactorial pathogenesis of PN-associated liver disease (PNALD). However, lipids are essential in early infant development, particularly in the neurocognitive development of preterm infants. Substitution of the lipid source from soybean oil to fish oil has emerged as a safe and efficacious treatment of PNALD, with marked improvements in morbidity and mortality. Knowledge of the developmental needs and physiologic limitations of preterm infants is crucial to optimizing parenteral lipid administration to nurture growth, and minimize and treat associated complications. The purpose of this review is to provide an overview of lipid requirements of the preterm infant and discuss the role of parenteral lipid emulsions in the management of PNALD and other diseases of prematurity.
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PMID:Role of parenteral lipid emulsions in the preterm infant. 2399 51

Parenteral nutrition (PN) is a life saving and support therapy for critical newborn infants. Parenteral nutrition-associated cholestasis (PNAC) is one of its common complications. This article focuses on the risk factors for PNAC in newborn infants in both non-nutrient and nutrient associated risk factors. The main risk factors include prematurity, small for gestational age, prolonged PN, diseases (especially sepsis and necrotizing enterocolitis), delayed or less proportional enteral nutrition, non cyclic PN, amino acids/lipids composition and dosage, energy supply and trace elements contents.
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PMID:[Risk factors for parenteral nutrition-associated cholestasis in neonates]. 2500 70

Over 30,000 patients are permanently dependent on Total Parenteral Nutrition (TPN) for survival with several folds higher requiring TPN for a prolonged duration. Unfortunately, it can cause potentially fatal complications. TPN infusion results in impairment of gut mucosal integrity, enhanced inflammation, increased cytokine expression and trans-mucosal bacterial permeation. It also causes endotoxin associated down regulation of bile acid transporters and Parenteral Nutrition Associated Liver Disease (PNALD), which includes steatosis, disrupted glucose metabolism, disrupted lipid metabolism, cholestasis and liver failure. Despite multiple theories, its etiology and pathophysiology remains elusive and is likely multifactorial. An important cause for TPN related pathologies appears to be a disruption in the normal enterohepatic circulation due to a lack of feeding during such therapy. This is further validated by the fact that in clinical settings, once cholestasis sets in, its reversal occurs when a patient is receiving a major portion of calories enterally. There are several other postulated mechanisms including gut bacterial permeation predisposing to endotoxin associated down regulation of bile acid transporters. An additional potential mechanism includes toxicity of the TPN solution itself, such as lipid mediated hepatic toxicity. Prematurity, leading to a poor development of bile acid regulating nuclear receptors and transporters has also been implicated as a causative factor. This review presents the current controversies and research into mechanisms of TPN associated injury.
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PMID:Controversies in the Mechanism of Total Parenteral Nutrition Induced Pathology. 2741 69


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