Parenteral Nutrition–Associated Cholestasis in Neonates: Multivariate Analysis of the Potential Protective Effect of Taurine

Spencer, Ariel U.; Yu, Sunkyung; Tracy, Thomas F.; Aouthmany, Moustafa M.; Llanos, Adolfo; Brown, Morton B.; Brown, Marilyn R.; Shulman, Robert J.; Hirschl, Ronald B.; DeRusso, Patricia A.; Cox, Jean T.; Dahlgren, Jacqueline; Strouse, Peter J.; Groner, Jonathan I.; Teitelbaum, Daniel H.

doi:10.1177/0148607105029005337

Cited by 74 publications

(49 citation statements)

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“…Consistent with reports of previous researchers, we found that the affected infants were more immature Early amino-acid support and cholestasis M Steinbach et al and had lower birth weight than the non-affected group. 5,[7][8][9] Other investigations have also described an association between cholestasis and the quantity and formulation of amino acids administered parenterally, excess caloric intake of fats and carbohydrates, 10,11 toxicity of trace minerals, [12][13][14][15][16] male gender, 17 perinatal asphyxia, 18 phototoxicity of multivitamin 2 Aggressive administration of parenteral amino acids to improve protein accretion rates in very preterm neonates has been supported in the literature. [24][25][26][27] Although tolerance of high-dose amino acids has been described, researchers acknowledge that sensitive tests to monitor amino-acid toxicity are not readily available in the clinical setting.…”

Section: Discussionmentioning

confidence: 99%

“…7 The use of parenteral nutrition solutions, which are lower in methionine and aromatic amino acids and higher in taurine, have been associated with a decreased incidence in liver dysfunction. 7 Glutamate and glutamine are important for cellular metabolism, and supplementation with glutamine in the parenteral solution has been recommended as a possible management strategy for neonates with prolonged cholestatic jaundice. 1,[32][33][34][35] We found that levels of blood urea nitrogen, citrulline, histidine, methionine and succinyl carnitine were higher on day 7 in neonates who developed cholestasis.…”

Section: Discussionmentioning

confidence: 99%

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Demographic and nutritional factors associated with prolonged cholestatic jaundice in the premature infant

et al. 2007

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Objective: The primary aim of this study was to determine if an association exists between amino-acid levels and development of cholestasis. The secondary aim of our amino-acid dose comparison trial was to identify factors associated with the development of prolonged cholestatic jaundice.Study Design: We compared demographic characteristics and amino-acid levels in neonates who developed cholestasis with those who did not. Parenteral-associated cholestatic liver disease was defined as a direct serum bilirubin above 5 mg per 100 ml any time during the first 28 days after birth in neonates with no history of biliary atresia or viral hepatitis. We obtained filter paper blood spots for amino acid and acylcarnitine measurements on the day of randomization and days 7 and 28 of age to identify a profile of values that could be used to identify neonates with evidence of abnormal liver function. Result:We enrolled 122 neonates in our study; 13 (10.7%) developed cholestasis. Neonates who developed cholestasis were more immature, had lower birth weight, were exposed to parenteral nutrition for a longer period, had a higher cumulative dose of amino acids, were less often on enteral nutrition by day 7 of age, more often had a patent ductus arteriosus and severe intraventricular hemorrhage and were more commonly treated with steroids by 28 days of age. Amino acid and acylcarnitine values were not different for the two groups on the day of randomization. On day 7 (parenteral phase of nutrition), blood urea nitrogen, citrulline, histidine, methionine and succinyl carnitine were higher, and serine, glutamate and thyroxine levels were lower in the neonates who developed cholestasis than in who did not. Conclusion:Cholestasis remains an important complication of parenteral nutrition, and several clinical and biochemical factors may be helpful in identifying high-risk patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Demographic and nutritional factors associated with prolonged cholestatic jaundice in the premature infant

et al. 2007

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“…However, to date, studies testing prophylactic strategies have not identified a consistently successful method, other than discontinuing the PN, which frequently is not a feasible option. Those studies included prophylactic administration of taurosusodeoxycholic acid, 5 cholecystokinin-octapeptide, 6,7 taurine, 8 phenobarbitol 9 and removing copper and manganese from the PN. 10,11 One problem inherent in any prophylactic strategy in the NICU is accurately predicting which neonates are at highest risk for developing the adverse outcome, so that high-risk patients can be eligible for study while low-risk patients can be excluded.…”

Section: Introductionmentioning

confidence: 99%

Identifying patients, on the first day of life, at high-risk of developing parenteral nutrition-associated liver disease

et al. 2007

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“…[108][109][110][111] Orally ingested methionine is converted to choline and taurine via hepatic trans-sulphuration pathways; however, when methionine is administered parenterally to the systemic circulation rather than to the portal circulation, it is transaminated to mercaptans, reducing the synthesis of these metabolites. Deficiencies of both taurine and choline have been documented in small (n 50) retrospective studies of patients receiving long-term HPN and are associated with increased biochemical markers of liver function.…”

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confidence: 99%

Review article: the management of long‐term parenteral nutrition

Dibb

Teubner

Theis

et al. 2013

Aliment Pharmacol Ther

137

108

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SummaryBackgroundHome parenteral nutrition (HPN) is currently the management of choice for patients with chronic intestinal failure.AimTo summarise the major issues in delivering long‐term parenteral nutrition (>3 months) and assess outcome as per complications, mortality and quality of life. To assess the evidence for the therapeutic use of trophic factors such as teduglutide and to review evolving therapeutic options in the treatment of chronic intestinal failure.MethodsA literature search using PubMed and MEDLINE databases was performed.ResultsSafe delivery of HPN relies upon individualised formulations of parenteral nutrition administered via carefully maintained central venous catheters by trained patients or carers, supported by a skilled multidisciplinary team. Early diagnosis and treatment of complications including catheter‐associated blood stream infection (reported incidence 0.14–0.83 episodes/patient‐year on HPN) and central venous thrombosis (reported incidence 0.03 episodes/patient‐year) is important to minimise mortality and morbidity. There is a significant variation in the reported incidence of both hepatobiliary complications (19–75%) and advanced liver disease (0–50%). Five‐year survival rates in large centres are reported between 60% and 78% with survival primarily related to underlying diagnosis. Long‐term survival remains higher on HPN than with intestinal transplantation. The role of intestinal lengthening procedures is yet to be validated in adults.ConclusionsHome parenteral nutrition delivered by skilled nutrition teams has low incidences of catheter‐related complications. Most deaths relate to the underlying disease. Therapies such as teduglutide and small bowel transplantation appear promising, but home parenteral nutrition appears likely to remain the bedrock of management in the near term.

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Parenteral Nutrition–Associated Cholestasis in Neonates: Multivariate Analysis of the Potential Protective Effect of Taurine

Abstract: Within specific subgroups of neonatal patients, taurine supplementation does offer a very significant degree of protection against PNAC. Patients with NEC or severe prematurity are most likely to benefit substantially from taurine supplementation.

Cited by 74 publications

References 33 publications

Demographic and nutritional factors associated with prolonged cholestatic jaundice in the premature infant

Demographic and nutritional factors associated with prolonged cholestatic jaundice in the premature infant

Identifying patients, on the first day of life, at high-risk of developing parenteral nutrition-associated liver disease

Review article: the management of long‐term parenteral nutrition

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