Lack Of Enteral Feeding Research Articles

Risk factors for neonatal cholestasis in small gestational age infants: case report and literature review

Cholestatic jaundice, defined as conjugated bilirubin levels higher than 1 mg/dl, is a bile formation and excretion disturbance. Its incidence is estimated at 1 case in 2500 live births, being 100-200 times higher in preterm infants less than 28 weeks gestational age. It occurs in biliary atresia, infectious diseases, endocrine and inherited metabolic diseases, Alagille Syndrome, preterm and intrauterine growth-restricted newborns, lack of enteral feeding, and is more frequent in male gender. It is a frequent complication of parenteral nutrition. In preterm and small for gestational age (SGA) infants, the etiology of cholestasis is multifactorial. Early diagnosis enables early therapeutic intervention. We report the case of an SGA male preterm infant. He was born by C-section for fetal distress at 30 weeks gestational age with an 800 g birth weight. He developed mild respiratory distress, hypoglycemia, meconium ileus, and early cholestasis. Complex hematological, serological, and immunological tests were carried out; ultrasound evaluations were performed. The final diagnosis was cholestasis of multifactorial etiology in a preterm infant with severe intrauterine growth restriction (IUGR). Treatment with ursodeoxycholic acid was started. Three months later, the transaminases, bilirubin, gammaglutamyl transferase (GGT), and alkaline phosphatase (ALP) triglycerides returned to normal. Conclusion. Cholestasis in SGA infants is a severe condition potentially associated with life-threatening complications, requiring complex diagnostic evaluation.

Parenteral nutrition-associated liver injury: clinical relevance and mechanistic insights.

Intestinal failure-associated liver disease (IFALD) is a relatively common complication in individuals receiving parenteral nutrition (PN). IFALD can be manifested as different types of liver injury, including steatosis, cholestasis, and fibrosis, and could result in liver failure in some cases. The onset and progression of IFALD are highly dependent on various patient and PN-related risk factors. Despite still being under investigation, several mechanisms have been proposed. Liver injury can originate due to caloric overload, nutrient deficiency, and toxicity, as well as phytosterol content, and omega-6 to omega-3 fatty acids ratio contained in lipid emulsions. Additional mechanisms include immature or defective bile acid metabolism, acute heart failure, infections, and sepsis exerting negative effects via Toll-like receptor 4 and nuclear factor κB inflammatory signaling. Furthermore, lack of enteral feeding, gut dysbiosis, and altered enterohepatic circulation that affect the farnesoid x receptor-fibroblast growth factor 19 axis can also contribute to IFALD. Various best practices can be adopted to minimize the risk of developing IFALD, such as prevention and management of central line infections and sepsis, preservation of intestine's length, a switch to oral and enteral feeding, cyclic PN, avoidance of overfeeding and soybean oil-based lipid formulations, and avoiding hepatotoxic substances. The present review thus provides a comprehensive overview of all relevant aspects inherent to IFALD. Further research focused on clinical observations, translational models, and advanced toxicological knowledge frameworks is needed to gain more insight into the molecular pathogenesis of hepatotoxicity, reduce IFALD incidence, and encourage the safe use of PN.

Role of the Gut Microbiota in Parenteral Nutrition–Associated Liver Disease: From Current Knowledge to Future Opportunities

Parenteral nutrition–associated liver disease (PNALD) refers to a spectrum of conditions that can develop cholestasis, steatosis, fibrosis, and cirrhosis in the setting of parenteral nutrition (PN) use. Patient risk factors include short bowel syndrome, bacterial overgrowth and translocation, disturbance of hepatobiliary circulation, and lack of enteral feeding. A growing body of evidence suggests an intricate linkage between the gut microbiota and the pathogenesis of PNALD. In this review, we highlight current knowledge on the taxonomic and functional changes in the gut microbiota that might serve as noninvasive biomarkers. We also discuss the function of microbial metabolites and associated signaling pathways in the pathogenesis of PNALD. By providing the perspectives of microbiota-host interactions in PNALD for basic and translational research and summarizing current limitations of microbiota-based approaches, this review paves the path for developing novel and precise microbiota-based therapies in PNALD.

Su1798 Glucagon-Like Peptides Ameliorate Total Prenteral Nutrition Associated Gut Atrophy

Background: Total parenteral nutrition (TPN) is a life-saving therapy in critically ill patients. Unfortunately, it is associated with significant morbidity and mortality, including gut atrophy and Parenteral Nutrition Associated Liver Disease. A lack of enteral feeding during TPN, disrupts key signaling molecules and the enterohepatic circulation, which appears to be a major contributor to disease pathology. Our group previously demonstrated thatenterally administeredbile acid,oleanolic acid (OA)significantly improved gut density andmorphology. OAis a ligand for the G-protein coupled receptor TGR-5. TGR-5 is known to induce transcription of glucagon-like peptide (GLP)-1 and GLP-2. While GLP-1 regulates hepatic steatosis and inflammation, GLP2 is involved in gut growth and motility.Hypothesis: We hypothesize that TPN infusion disrupts the TGR5-GLP axis and exogenous GLP-1, GLP-2 infusion will ameliorate TPN induced injury. Methods: Seven to ten day old piglets were implanted with jugular venous (JVC) and duodenal catheters (DC). Animals were randomized to receive Enteral Feeding (EN) or TPN. The TPN group was subdivided into TPN plus GLP-1 and GLP-2 (n=3). Milk was delivered via the DC and TPN was infused via the JVC. GLP-1 and GLP-2 were dosed at3 mcg/kg/day and 30 mcg/kg/day respectively. Results: Mean daily weight gain (grams) for control Enteral Fed (EN) vs TPN animals and standard deviation (±SD) was 102.4±10.8, 91.03±12.1 respectively, p>0.05. Marked gut atrophy was noted with TPN.Mean gut density as measured in grams/cm of gut tissue and standard deviation (±SD) in EN vs TPN was 0.35±0.03, 0.185±0.05, p<0.05. GLP treatment caused a robust increase in gut density(0.28±0.07). Conclusion: GLP treatment improves gut atrophy in TPN infused animals. This result also provides mechanistic validation for effects of OA treatment. We believe that modulation of TPN associated pathology via bile acid regulation of signaling molecules is novel and could bring a paradigm change in current treatment strategies for unfortunatecomplication of a lifesaving therapy.

Su1799 Liver-Specific Nuclear Lamin a Deficiency Causes Male-Selective Hepatic Steatosis via Induction of Lipogenic Genes

Background: Total parenteral nutrition (TPN) is a life-saving therapy in critically ill patients. Unfortunately, it is associated with significant morbidity and mortality, including gut atrophy and Parenteral Nutrition Associated Liver Disease. A lack of enteral feeding during TPN, disrupts key signaling molecules and the enterohepatic circulation, which appears to be a major contributor to disease pathology. Our group previously demonstrated thatenterally administeredbile acid,oleanolic acid (OA)significantly improved gut density andmorphology. OAis a ligand for the G-protein coupled receptor TGR-5. TGR-5 is known to induce transcription of glucagon-like peptide (GLP)-1 and GLP-2. While GLP-1 regulates hepatic steatosis and inflammation, GLP2 is involved in gut growth and motility.Hypothesis: We hypothesize that TPN infusion disrupts the TGR5-GLP axis and exogenous GLP-1, GLP-2 infusion will ameliorate TPN induced injury. Methods: Seven to ten day old piglets were implanted with jugular venous (JVC) and duodenal catheters (DC). Animals were randomized to receive Enteral Feeding (EN) or TPN. The TPN group was subdivided into TPN plus GLP-1 and GLP-2 (n=3). Milk was delivered via the DC and TPN was infused via the JVC. GLP-1 and GLP-2 were dosed at3 mcg/kg/day and 30 mcg/kg/day respectively. Results: Mean daily weight gain (grams) for control Enteral Fed (EN) vs TPN animals and standard deviation (±SD) was 102.4±10.8, 91.03±12.1 respectively, p>0.05. Marked gut atrophy was noted with TPN.Mean gut density as measured in grams/cm of gut tissue and standard deviation (±SD) in EN vs TPN was 0.35±0.03, 0.185±0.05, p<0.05. GLP treatment caused a robust increase in gut density(0.28±0.07). Conclusion: GLP treatment improves gut atrophy in TPN infused animals. This result also provides mechanistic validation for effects of OA treatment. We believe that modulation of TPN associated pathology via bile acid regulation of signaling molecules is novel and could bring a paradigm change in current treatment strategies for unfortunatecomplication of a lifesaving therapy.

Starvation Compromises Paneth Cells

Lack of enteral feeding, with or without parenteral nutritional support, is associated with increased intestinal permeability and translocation of bacteria. Such translocation is thought to be important in the high morbidity and mortality rates of patients who receive nothing by mouth. Recently, Paneth cells, important constituents of innate intestinal immunity, were found to be crucial in host protection against invasion of both commensal and pathogenic bacteria. This study investigates the influence of food deprivation on Paneth cell function in a mouse starvation model. Quantitative PCR showed significant decreases in mRNA expression of typical Paneth cell antimicrobials, lysozyme, cryptdin, and RegIIIγ, in ileal tissue after 48 hours of food deprivation. Protein expression levels of lysozyme and RegIIIγ precursor were also significantly diminished, as shown by Western blot analysis and IHC. Late degenerative autophagolysosomes and aberrant Paneth cell granules in starved mice were evident by electron microscopy, Western blot analysis, and quantitative PCR. Furthermore, increased bacterial translocation to mesenteric lymph nodes coincided with Paneth cell abnormalities. The current study demonstrates the occurrence of Paneth cell abnormalities during enteral starvation. Such changes may contribute to loss of epithelial barrier function, causing the apparent bacterial translocation in enteral starvation.

Colonization of the Gastrointestinal Tract in Neonates

Bacterial colonization of the neonatal gastrointestinal tract has emerged as an issue involving nutrition, immunity, and overall mortality. Bacterial organisms colonizing the gastrointestinal tract play a vital role in maintaining intestinal homeostasis, including digestion, nutrient absorption, and immunological mechanisms. In neonates, these bacteria are essential in postnatal development of intestinal mucosa and gut-associated lymphoid tissue critical for immunological protection. Colonization of bacteria is thought to occur over the first 1 to 2 weeks of life. Delivery mode, feeding method, and environment affect the succession and establishment of the beneficial bacteria in the neonate. Neonates delivered vaginally are colonized by the bacteria from the mother, whereas neonates delivered via caesarean section initially colonize with bacteria from the environment. Feeding method is another factor; Bifidobacterium species are believed to dominate the microflora of breastfed infants by day of life 2 to 3 and are thought to be critical in postnatal immunology. Formula-fed infants often have a more diverse microflora and a less obvious presence of the Bifidobacterium. Compared with healthy, term neonates, preterm infants have a significant delay in bacterial colonization. The effects of an immature gastrointestinal track, lack of enteral feeding, and the frequent use of antibiotic therapy are believed to contribute to the delay and imbalance in the microflora of preterm infants. Prolonged exposure to hospital bacteria increases the risk of colonization with strains specific to hospital flora.

Delayed Postnatal Presentation of Biliary Atresia in 2 Premature Neonates

Delayed Postnatal Presentation of Biliary Atresia in 2 Premature Neonates

Decreased expression of Paneth cell antimicrobial peptides coincide with bacterial translocation after starvation

The lack of enteral feeding, with or without parenteral nutritional support has been reported to result in increased translocation of bacteria, which is considered to play an important role in the high morbidity and mortality rates of critical illnesses such as acute pancreatitis. Recently, Paneth cells, important constituents of the innate intestinal immunity, were shown to be crucial in host protection against invasion of both commensal and pathogenic bacteria.This study investigates the influence of food deprivation on Paneth cell function and small intestinal integrity. Significant decreases in RNA expression of lysozyme (p&lt; 0.01), cryptdin (p&lt; 0.05) and RegIIIγ (p&lt;0.05) were seen after 48 hours of food deprivation in C57BL/6 mice (n=15/group). Accordingly, protein expression of lysozyme and the precursor form of RegIIIγ were also shown to decrease significantly (p&lt;0.01, p&lt;0.05 respectively). Furthermore, increased bacterial translocation to mesenteric lymph nodes occurred (p&lt;0.01), while HE staining showed normal intestinal architecture, distribution and expression of respectively tight junction proteins zonula occludens‐1 and claudin‐3 were unchanged.In conclusion, the current study demonstrates that enteral starvation causes Paneth cell dysfunction paralleled by increased bacterial translocation without disturbances of the small intestinal physical barrier.

T1286 Up-Regulation of Intestinal Toll-Like Receptors and Cytokines Expressions Change After TPN Administration and a Lack of Enteral Feeding

T1286 Up-Regulation of Intestinal Toll-Like Receptors and Cytokines Expressions Change After TPN Administration and a Lack of Enteral Feeding

Up-Regulation of Intestinal Toll-Like Receptors and Cytokines Expressions Change After TPN Administration and a Lack of Enteral Feeding

Total parenteral nutrition (TPN) increases the risk of severe infectious complications such as septic shock, which are believed to be the result of a breakdown of intestinal barrier function and subsequent bacterial translocation. Toll-like receptors (TLRs) comprise a family of membrane proteins that serve as pattern recognition receptors for a variety of microbe-derived molecules and stimulate innate immune responses to microbes. Alteration of intraepithelial lymphocytes (IELs) to TPN administration has been studied extensively. However, few studies have examined the effect of TPN administration on intestinal TLRs. We hypothesized that the expressions of intestinal TLRs and cytokines may change with TPN administration and a lack of enteral feeding. TPN-treated mice and sham operation mice (control) were killed at 10 days after operation. mRNA expression of intestinal cytokines and TLRs were analyzed with reverse transcription-polymerase chain reaction (RT-PCR) methods. Change in IEL populations was analyzed with flow cytometry. RT-PCR showed varying expression levels of TLRs at different sites on the small intestine and colon. TLR4, TLR5, TLR7, and TLR9 mRNAs were up-regulated in response to TPN administration, particularly in the distal small intestine. Up-regulation of TLRs in intestine in response to TPN administration and a lack of enteral nutrition may be associated with an increased risk of septic shock due to bacterial translocation caused by Interferon gamma-mediated intestinal epithelial cell apoptosis.

Relevance of Nutritional Route and Intercellular Adhesion Molecule-1 in Patients With Acute Renal Failure and Its Prognostic Implications

Nutritional support and the route of nutrition are important conditions for patients with acute renal failure (ARF) in intensive care units (ICUs). Enteral nutrition (EN) is the primary route of nutrition in these patients because of a lower rate of complications. A lack of enteral feeding was reported to increase intercellular adhesion molecule-1 (ICAM-1) in experimental models. Serum soluble ICAM-1 (sICAM-1) level is an independent predictor of mortality in predialysis patients. However, the effect of nutritional route on serum ICAM-1 level is unknown in ARF patients. The aim of this study was to investigate the relationship between route of nutrition and serum ICAM-1 level and its prognostic implications in ICU ARF patients. In total, 64 ICU patients with ARF were assessed according to their clinical features, route of nutrition, laboratory parameters, serum sICAM-1 levels, presence of infection, Acute Physiology and Chronic Health Evaluation (APACHE) III scores, and outcomes on their first nephrology consultation day. Thirty-two patients died during the follow-up period. The mortality rate and infection rate were higher in the parenteral nutrition (PN) group compared with the EN group (64% vs 42%, P = .05, and 84% vs 64%, P = .05, respectively). The route of nutrition influenced the serum sICAM-1 level. Parenteral nutrition was associated with a higher serum sICAM-1 level compared to EN (434 ng/mL [range 255 to 1,240] vs 217 ng/mL [range 123 to 296], respectively, P = .0004). The APACHE III score was found to be an independent prognostic factor among the parameters of nutritional route, presence of infection, serum albumin level, and serum sICAM-1 level. Patients with ARF as supported by PN had a lower serum albumin level, and a higher APACHE III score, sICAM-1 level, and mortality and infection rate. Serum sICAM-1 levels did not independently predict mortality in the present set of ARF patients.

Parenteral Nutrition and Fasting Reduces Mucosal Addressin Cellular Adhesion Molecule‐1 (MAdCAM‐1) mRNA in Peyer's Patches of Mice

Mucosal addressin cellular adhesion molecule-1 (MAdCAM-1) in Peyer's patches (PP) is the gateway molecule for cellular migration into the mucosal immune system. Lack of enteral feeding during parenteral nutrition (PN) rapidly decreases PP MAdCAM-1, leading to drops in mucosal T and B cells and intestinal and respiratory IgA. We determined the molecular events associated with MAdCAM-1 mRNA and protein during PN (short and long term) and fasting (1 and 2 days). Experiment 1: Cannulated mice received PN for 8 hours (short-term PN, n = 6) or chow + saline (chow, n = 6). Experiment 2: Cannulated mice received PN (long-term PN, n = 4) or chow (n = 3) for 5 days. Experiment 3: Noncannulated chow mice were fasted for 1 and 2 days (n = 2/time). Total cellular RNA from the PP was quantified for MAdCAM-1 mRNA by real-time polymerase chain reaction (PCR). MAdCAM-1 protein was measured by Western blot. PN rapidly down-regulated MAdCAM-1 gene expression. After 8 hours of PN with lack of enteral feeding, MAdCAM-1 mRNA levels dropped 20% (0.8-fold vs chow, p > .05); 5 days of PN reduced MAd-CAM-1 levels 64% (0.34-fold vs chow, p < .05). PN reduced MAdCAM-1 protein levels by 30% (chow: 329 +/- 14 vs PN: 230 +/- 35, p < .05) after 5 days. Fasting of uncannulated mice decreased MAdCAM-1 mRNA levels by 16% (0.84-fold, p < .05) at day 1 and 30% (0.7-fold, p < .05) by day 2 compared with chow. Both PN with lack of enteral feeding and fasting down-regulate MAdCAM-1 mRNA and protein levels in PP. The MAdCAM-1 changes are due to lack of enteral stimulation rather than toxic effects of PN.

Neonatal Candidiasis Among Extremely Low Birth Weight Infants: Risk Factors, Mortality Rates, and Neurodevelopmental Outcomes at 18 to 22 Months

Neonatal candidiasis is associated with substantial morbidity and mortality rates. Neurodevelopmental follow-up data for a large multicenter cohort have not been reported. Data were collected prospectively for neonates born at <1000 g at National Institute of Child Health and Human Development-sponsored Neonatal Research Network sites between September 1, 1998, and December 31, 2001. Uniform follow-up evaluations, including assessments of mental and motor development with the Bayley Scales of Infant Development II, were completed for all survivors at corrected ages of 18 to 22 months. We evaluated risk factors for the development of neonatal candidiasis, responses to antifungal therapy, and the association between candidiasis and subsequent morbidity and death. The cohort consisted of 4579 infants; 320 of 4579 (7%) developed candidiasis; 307 of 320 had Candida isolated from blood, 27 of 320 had Candida isolated from cerebrospinal fluid, and 13 (48%) of 27 of those with meningitis had negative blood cultures. In multivariate analysis of risk factors on day of life 3, birth weight, cephalosporins, gender, and lack of enteral feeding were associated with development of candidiasis. After diagnosis, most neonates had multiple positive cultures despite antifungal therapy, and 10% of neonates had candidemia for > or =14 days. Death or neurodevelopmental impairment (NDI) was observed for 73% of extremely low birth weight infants who developed candidiasis. Death and NDI rates were greater for infants who had delayed removal or replacement of central catheters (>1 day after initiation of antifungal therapy), compared with infants whose catheters were removed or replaced promptly. Blood cultures were negative for approximately one half of the infants with Candida meningitis. Persistent candidiasis was common. Delayed catheter removal was associated with increased death and NDI rates.

Lack of enteral nutrition—effects on the intestinal immune system

Total parenteral nutrition (TPN) results in a loss of mucosal immune function by alterations in both phenotype and function of intraepithelial lymphocytes (IEL). We hypothesized that the observed changes with TPN administration are caused by the lack of enteral feeding, and not to the TPN solution itself. Mice received oral feeding (Control), TPN alone (TPN), or TPN plus oral feeding (TPN+Food). Mice were killed after 7 days, and bacteriological cultures from spleen, liver, and mesenteric lymph nodes obtained, with bacterial translocation (BT) being defined as a positive culture. IEL phenotype was analyzed by flow cytometry. IEL messenger RNA (mRNA) cytokine expression used reverse transcriptase polymerase chain reaction (RT-PCR). Apoptosis was detected by terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) staining. BT significantly (P < 0.05, with analysis of variance [ANOVA]) increased in the TPN group (53%) compared with Control (9%) and TPN+Food (14%) groups. TPN also resulted in a significant (P < 0.01) increase in epithelial cell apoptosis: TPN 7.6 +/- 1.1% versus Control 2.9 +/- 1.1% and TPN+Food 2.1 +/- 0.3% (mean +/- SD). Height of the villus-crypt complex was significantly decreased in TPN mice (315 +/- 16 microm) compared with Control (431 +/- 27 microm) and TPN+Food (421 +/- 26 microm) groups. IEL phenotypes significantly changed with TPN administration: CD4+ CD8- as well as CD4+ CD8+ subpopulations were reduced compared with Control or TPN+Food mice; as were the CD8alphabeta+ thymus-dependent, and CD8+ CD44+ mature IEL. IEL cytokine mRNA expression was also significantly altered with TPN: IL-2 and IL-10 expression declined, and IL-4 IL-6, interferon gamma (IFN-gamma), transforming growth factor beta-1 (TGF-beta1), and tumor necrosis factor-alpha (TNF-alpha) were increased, when compared with Control or TPN+Food mice. This study demonstrates that the major factor responsible for TPN-induced BT and IEL-changes is the lack of enteral feeding and not the administration of the TPN solution itself.

New Approaches to Parenteral Nutrition in Infants and Children

Parenteral nutrition (PN) has become a mainstay in the treatment of children with intestinal failure or conditions that preclude enteral feeding. Estimated energy and protein requirements can usually be met, unless the patient is fluid volume restricted or glucose intolerant. Although PN is generally well‐tolerated, in some patients it is still associated with a significant morbidity. Complications include metabolic disturbances, venous access device infection or dysfunction, venous thrombosis, and cholestatic liver disease. Patients need to be carefully monitored for evidence of micronutrient deficiencies or excesses. There is a close relationship between line sepsis and thrombosis. Strict aseptic technique is the key to preventing line infections. Recurrent sepsis and thrombosis may eventually lead to loss of venous access and may jeopardize the long‐term delivery of PN. Chronic cholestatic liver disease is common in premature infants with gastrointestinal problems, recurrent sepsis, and lack of enteral feeding. The etiology is multifactorial. Early enteral feeding is the most effective strategy in preventing PN‐associated liver disease. New specialized nutrient solutions and lipid emulsions promise improved clinical outcomes. However, long‐term clinical data are not yet available in children. In recent years, nutrition support teams have improved clinical and economic outcomes by encouraging the appropriate use and monitoring of PN therapy. In patients with intestinal failure, parent‐administered home PN has become an alternative to long‐term hospitalization. Apart from a positive effect on the quality of life of patient and family, home PN is cost‐effective and reduces the risk of nosocomial infections and catheter‐related complications.

New approaches to parenteral nutrition in infants and children.

Parenteral nutrition (PN) has become a mainstay in the treatment of children with intestinal failure or conditions that preclude enteral feeding. Estimated energy and protein requirements can usually be met, unless the patient is fluid volume restricted or glucose intolerant. Although PN is generally well tolerated, in some patients it is still associated with a significant morbidity. Complications include metabolic disturbances, venous access device infection or dysfunction, venous thrombosis and cholestatic liver disease. Patients need to be carefully monitored for evidence of micronutrient deficiencies or excesses. There is a close relationship between line sepsis and thrombosis. Strict aseptic technique is the key to preventing line infections. Recurrent sepsis and thrombosis may eventually lead to loss of venous access and may jeopardize the long-term delivery of PN. Chronic cholestatic liver disease is common in premature infants with gastrointestinal problems, recurrent sepsis and lack of enteral feeding. The aetiology is multifactorial. Early enteral feeding is the most effective strategy in preventing PN-associated liver disease. New specialized nutrient solutions and lipid emulsions promise improved clinical outcomes. However, long-term clinical data are not yet available in children. In recent years, nutrition support teams have improved clinical and economic outcomes by encouraging the appropriate use and monitoring of PN therapy. In patients with intestinal failure, parent-administered home PN has become an alternative to long-term hospitalization. Apart from a positive effect on the quality of life of patient and family, home PN is cost-effective and reduces the risk of nosocomial infections and catheter-related complications.

Impairment of mucosal immunity by parenteral nutrition: depressed nasotracheal influenza-specific secretory IgA levels and transport in parenterally fed mice.

To examine the effects on mucosal selective transport of polymeric IgA (pIgA) and the ability of exogenous pIgA to provide protection despite altered mucosal transport. Parenteral nutrition significantly impairs established antipseudomonal immunity and IgA-mediated antiviral immunity in association with gut-associated lymphoid tissue mass atrophy. Lack of enteral feeding also induces mucosal effects. After immunization, nasotracheal levels of influenza-specific IgA were measured in cannulated mice randomized to chow feeding or parenteral nutrition. Nonimmune animals were randomized to chow or total parenteral nutrition, and after 5 days of diet were given a mixture of two antiinfluenza monoclonal antibodies, pIgA and IgG. Four hours after injection, nasal washes were collected and influenza-specific antibody levels were determined by enzyme-linked immunosorbent assay to calculate the selective transport index of IgA relative to IgG. In the final experiment, immunized animals were randomized to chow or parenteral feeding, and after 5 days, parenterally fed animals received either normal mouse serum or antiviral pIgA before viral challenge. Viral shedding was measured at 42 hours after challenge. Parenteral nutrition significantly reduced virus-specific IgA in nasotracheal washes. Parenteral nutrition depressed the selective transport index, demonstrating impaired mucosal transport of pIgA. Parenterally fed animals given specific antiviral pIgA but not normal mouse serum eliminated virus from the airway and regained mucosal protection, demonstrating adequate residual transport for immunity if adequate pIgA is present. Although both decreased IgA production due to gut-associated lymphoid tissue atrophy and impaired mucosal transport occur when enteral feeding is not provided, residual transport can provide antiviral protection if exogenous antiviral pIgA is available. Production, rather than transport, may be the most important factor in maintaining established respiratory tract IgA-mediated immunity.

Liver enzyme abnormalities in gram-negative bacteremia of premature infants.

Hyperbilirubinemia and liver enzyme abnormalities are commonly observed in sepsis. However, the frequency in premature neonates and the specific relation to gram-negative bacteria are not known. Charts of all preterm infants who had positive blood cultures for either gram-negative bacteria or coagulase-negative staphylococci were reviewed. Neonates with gram-negative bacteremia (n = 54) were compared with neonates with coagulase-negative staphylococcal bacteremia (n = 31). In addition infants with gram-negative bacteremia and elevated liver enzymes (n = 25) were compared with infants with gram-negative bacteremia and normal liver enzymes (n = 29). Liver enzyme abnormalities accompanied 46.3% (25 of 54) of gram-negative bacteremia and 12.9% (4 of 31) of episodes of coagulase-negative staphylococcal bacteremia (P = 0.002). Serum concentrations of liver enzymes were significantly higher in infants with gram-negative bacteremia than in those with coagulase-negative staphylococcal bacteremia (P < 0.0001), but no difference in alkaline phosphatase serum values was observed. Infants with gram-negative bacteremia and elevated liver enzymes were not fed for a longer period than infants with gram-negative bacteremia and normal liver enzymes (7.3 +/- 6.3 days vs. 4.0 +/- 4.3 days, P = 0.03), and this was accompanied by significant conjugated hyperbilirubinemia (P < 0.0001). Ventilation, total parenteral nutrition and medications were not responsible for the observed differences. Klebsiella pneumoniae bacteremia was commonly associated with elevated liver enzymes (12 of 18), whereas none of the infants with Pseudomonas aeruginosa bacteremia had elevated liver enzymes. Gram-negative bacteremia is commonly associated with cholestasis in premature neonates. Liver enzyme abnormalities are more common than elevated conjugated bilirubin, not all gram-negative bacteria have the same effect and the lack of enteral feeding seems to play a more significant role than the administration of parenteral nutrition.

Early cholestasis in premature infants receiving total parenteral nutrition: a possible consequence of shock and hypoxia.

We report 18 premature infants (gestational age: 31.1 weeks +/- 2.6 [mean +/- SD] (range: 28-36]) with necrotizing enterocolitis (NEC) who developed total parenteral nutrition (TPN) associated cholestasis. Liver function tests were performed at the start of TPN (D1) and repeated once a week. Considering the date of cholestasis onset (direct bilirubin > 30 mumol/l and/or serum bile salts > 10 mumol/l), the patients can be divided in two groups. The first group consisted of 9 patients who had cholestasis at D1. In these patients shock and/or hypoxia occurred prior to D1 and were the only risk factors of cholestasis identified before D1. The second group consisted of 9 patients who developed cholestasis after D1 and in whom the cause of cholestasis was multifactorial (sepsis, lack of enteral feeding, shock and/or hypoxia). These results suggest that shock and/or hypoxia can be responsible for early cholestasis in premature infants. We conclude that shock and hypoxia should be considered when discussing TPN-associated cholestasis.