Neonatal Cholestasis: Definition, Clinical Manifestation and Management; A Mini Review
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Abstract
Physiological jaundice of the newborn is a complex benign disease that rarely persists in the second week of life. Neonatal cholestasis (NC) is caused by a disorder in the formation of bile by liver cells or obstruction of the flow of bile through the intrahepatic or extrahepatic biliary tree, which leads to the accumulation of bile substances in the liver, blood, and extrahepatic tissues. This state may continue until the first six months of infancy, and its vulnerability to other cholestatic agents increases. This fact makes NC an uncommon feature of neonatal liver disease rather than a late manifestation. The aim of this paper is to review the definitions, etiologies, clinical manifestations, treatment, and management strategies for NC infants.
1. Zollner G, Trauner M. Mechanisms of cholestasis. Clinics in liver disease. 2008;12(1):1-26.
2. Hoerning A, Raub S, Dechêne A, Brosch MN, Kathemann S, Hoyer PF, et al. Diversity of disorders causing neonatal cholestasis–the experience of a tertiary pediatric center in Germany. Frontiers in Pediatrics. 2014;2:65.
3. Moyer V, Freese DK, Whitington PF, Olson AD, Brewer F, Colletti RB, et al. Guideline for the evaluation of cholestatic jaundice in infants: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. Journal of pediatric gastroenterology and nutrition. 2004;39(2):115-28.
4. McKiernan P, editor Neonatal cholestasis. Seminars in neonatology; 2002: Elsevier.
5. Lee WS. Pre‐admission consultation and late referral in infants with neonatal cholestasis. Journal of paediatrics and child health. 2008;44(1‐2):57-61.
6. Lee WS. Pre-admission consultation and late referral in infants with neonatal cholestasis. Journal of paediatrics and child health. 2008;44(1-2):57-61.
7. Sokol RJ, Shepherd RW, Superina R, Bezerra JA, Robuck P, Hoofnagle JH. Screening and outcomes in biliary atresia: summary of a National Institutes of Health workshop. Hepatology. 2007;46(2):566-81.
8. Harpavat S, Finegold MJ, Karpen SJ. Patients with biliary atresia have elevated direct/conjugated bilirubin levels shortly after birth. Pediatrics. 2011;128(6):e1428-e33.
9. Li MK, Crawford JM, editors. The pathology of cholestasis. Seminars in liver disease; 2004: Copyright© 2004 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New ….
10. Wagner M, Zollner G, Trauner M. New molecular insights into the mechanisms of cholestasis. Journal of hepatology. 2009;51(3):565-80.
11. Feldman AG, Sokol RJ. Neonatal Cholestasis. NeoReviews. 2013;14(2).
12. Rodríguez-Garay EA. Cholestasis: human disease and experimental animal models. Annals of Hepatology. 2003;2(4):150-8.
13. Pollock G, Minuk GY. Diagnostic considerations for cholestatic liver disease. Journal of Gastroenterology and Hepatology. 2017;32(7):1303-9.
14. Erlichman J, Loomes KM, Rand EB. Causes of cholestasis in neonates and young infants. Dostupno na: https://www uptodate com. 2016.
15. Feldman AG, Sokol RJ. Neonatal Cholestasis: Updates on Diagnostics, Therapeutics, and Prevention. NeoReviews. 2021;22(12):e819-e36.
16. McKiernan PJ. Neonatal cholestasis. Seminars in neonatology : SN. 2002;7(2):153-65.
17. Feldman AG, Sokol RJ. Neonatal cholestasis. NeoReviews. 2013;14(2):e63-e73.
18. Betalli P, Davenport M. Biliary atresia and other congenital disorders of the extrahepatic biliary tree. Pediatric Hepatology and Liver Transplantation. 2019:129-44.
19. Esmaili J, Izadyar S, Karegar I, Gholamrezanezhad A. Biliary atresia in infants with prolonged cholestatic jaundice: diagnostic accuracy of hepatobiliary scintigraphy. Abdominal imaging. 2007;32:243-7.
20. Harpavat S, Garcia-Prats JA, Anaya C, Brandt ML, Lupo PJ, Finegold MJ, et al. Diagnostic yield of newborn screening for biliary atresia using direct or conjugated bilirubin measurements. Jama. 2020;323(12):1141-50.
21. Wada H, Muraji T, Yokoi A, Okamoto T, Sato S, Takamizawa S, et al. Insignificant seasonal and geographical variation in incidence of biliary atresia in Japan: a regional survey of over 20 years. Journal of pediatric surgery. 2007;42(12):2090-2.
22. Fabris L, Fiorotto R, Spirli C, Cadamuro M, Mariotti V, Perugorria MJ, et al. Pathobiology of inherited biliary diseases: a roadmap to understand acquired liver diseases. Nature Reviews Gastroenterology & Hepatology. 2019;16(8):497-511.
23. El-Guindi MA-S, Sira MM, Sira AM, Salem TA-H, El-Abd OL, Konsowa HA-S, et al. Design and validation of a diagnostic score for biliary atresia. Journal of hepatology. 2014;61(1):116-23.
24. Delemos AS, Friedman LS. Systemic causes of cholestasis. Clinics in liver disease. 2013;17(2):301-17.
25. Guthrie G, Burrin D. Impact of parenteral lipid emulsion components on cholestatic liver disease in neonates. Nutrients. 2021;13(2):508.
26. Serinet M-O, Wildhaber BE, Broue P, Lachaux A, Sarles J, Jacquemin E, et al. Impact of age at Kasai operation on its results in late childhood and adolescence: a rational basis for biliary atresia screening. Pediatrics. 2009;123(5):1280-6.
27. Suchy FJ. Neonatal cholestasis. Pediatrics in review. 2004;25(11):388-96.
28. Lane E, Murray KF. Neonatal cholestasis. Pediatric Clinics. 2017;64(3):621-39.
29. Venigalla S, Gourley GR, editors. Neonatal cholestasis. Seminars in perinatology; 2004: Elsevier.
30. Suchy FJ, Balistreri WF, Heubi JE, Searcy JE, Levin RS. Physiologic cholestasis: elevation of the primary serum bile acid concentrations in normal infants. Gastroenterology. 1981;80(5 pt 1):1037-41.
31. Suchy FJ. Neonatal cholestasis. Pediatrics in review. 2004;25(11):388-96.
32. Fawaz R, Baumann U, Ekong U, Fischler B, Hadzic N, Mack CL, et al. Guideline for the evaluation of cholestatic jaundice in infants: joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. Journal of pediatric gastroenterology and nutrition. 2017;64(1):154-68.
33. Fawaz R, Baumann U, Ekong U, Fischler B, Hadzic N, Mack CL, et al. Guideline for the Evaluation of Cholestatic Jaundice in Infants: Joint Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. Journal of pediatric gastroenterology and nutrition. 2017;64(1):154-68.
34. Ghazy RM, Khedr MA. Neonatal cholestasis: recent insights. Egyptian Pediatric Association Gazette. 2019;67(1):9.
35. Pandita A, Gupta V, Gupta G. Neonatal Cholestasis: A Pandora's Box. Clinical medicine insights Pediatrics. 2018;12:1179556518805412.
36. Suchy FJ, Balistreri WF, Heubi JE, Searcy JE, Levin RS. Physiologic cholestasis: elevation of the primary serum bile acid concentrations in normal infants. Gastroenterology. 1981;80(5):1037-41.
37. Harpavat S, Finegold MJ, Karpen SJ. Patients with biliary atresia have elevated direct/conjugated bilirubin levels shortly after birth. Pediatrics. 2011;128(6):e1428-33.
38. Ghazy RM, Khedr MA. Neonatal cholestasis: recent insights. Egyptian Pediatric Association Gazette. 2019;67:1-14.
39. Landing BH, Wells TR, Ramicone E. Time course of the intrahepatic lesion of extrahepatic biliary atresia: a morphometric study. Pediatric pathology. 1985;4(3-4):309-19.
40. Götze T, Blessing H, Grillhösl C, Gerner P, Hoerning A. Neonatal cholestasis–differential diagnoses, current diagnostic procedures, and treatment. Frontiers in pediatrics. 2015;3:43.
41. De Bruyne R, Van Biervliet S, Vande Velde S, Van Winckel M. Clinical practice: neonatal cholestasis. European journal of pediatrics. 2011;170:279-84.
42. Feldman AG, Sokol RJ, editors. Recent developments in diagnostics and treatment of neonatal cholestasis. Seminars in pediatric surgery; 2020: Elsevier.
43. Dani C, Pratesi S, Raimondi F, Romagnoli C, Neonatology TFfHotISo. Italian guidelines for the management and treatment of neonatal cholestasis. Italian Journal of pediatrics. 2015;41:1-12.
44. Feranchak AP, Sokol RJ, Suchy F. Medical and nutritional management of cholestasis in infants and children. Liver disease in children. 2007;3:190-231.
45. Best C. Management of neonatal cholestasis. Clinical Practice. 2009;6(1):75.
46. Balistreri WF. Neonatal cholestasis. The Journal of pediatrics. 1985;106(2):171-84.
47. Sokol RJ, Shepherd RW, Superina R, Bezerra JA, Robuck P, Hoofnagle JH. Screening and outcomes in biliary atresia: summary of a National Institutes of Health workshop. Hepatology. 2007;46(2):566-81.
48. Bhatia V, Bavdekar A, Pediatrics SKYftPGCoIAo. Management of acute liver failure in infants and children: consensus statement of the pediatric gastroenterology chapter, Indian academy of pediatrics. Indian pediatrics. 2013;50:477-82.
49. Bijl E, Bharwani K, Houwen R, De Man R. The long-term outcome of the Kasai operation in patients with biliary atresia: a systematic review. Neth J Med. 2013;71(4):170-3.
50. Zerbini M, Gallucci S, Maezono R, Ueno C, Porta G, Maksoud JG, et al. Liver biopsy in neonatal cholestasis: a review on statistical grounds. Modern Pathology: an Official Journal of the United States and Canadian Academy of Pathology, Inc. 1997;10(8):793-9.
2. Hoerning A, Raub S, Dechêne A, Brosch MN, Kathemann S, Hoyer PF, et al. Diversity of disorders causing neonatal cholestasis–the experience of a tertiary pediatric center in Germany. Frontiers in Pediatrics. 2014;2:65.
3. Moyer V, Freese DK, Whitington PF, Olson AD, Brewer F, Colletti RB, et al. Guideline for the evaluation of cholestatic jaundice in infants: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. Journal of pediatric gastroenterology and nutrition. 2004;39(2):115-28.
4. McKiernan P, editor Neonatal cholestasis. Seminars in neonatology; 2002: Elsevier.
5. Lee WS. Pre‐admission consultation and late referral in infants with neonatal cholestasis. Journal of paediatrics and child health. 2008;44(1‐2):57-61.
6. Lee WS. Pre-admission consultation and late referral in infants with neonatal cholestasis. Journal of paediatrics and child health. 2008;44(1-2):57-61.
7. Sokol RJ, Shepherd RW, Superina R, Bezerra JA, Robuck P, Hoofnagle JH. Screening and outcomes in biliary atresia: summary of a National Institutes of Health workshop. Hepatology. 2007;46(2):566-81.
8. Harpavat S, Finegold MJ, Karpen SJ. Patients with biliary atresia have elevated direct/conjugated bilirubin levels shortly after birth. Pediatrics. 2011;128(6):e1428-e33.
9. Li MK, Crawford JM, editors. The pathology of cholestasis. Seminars in liver disease; 2004: Copyright© 2004 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New ….
10. Wagner M, Zollner G, Trauner M. New molecular insights into the mechanisms of cholestasis. Journal of hepatology. 2009;51(3):565-80.
11. Feldman AG, Sokol RJ. Neonatal Cholestasis. NeoReviews. 2013;14(2).
12. Rodríguez-Garay EA. Cholestasis: human disease and experimental animal models. Annals of Hepatology. 2003;2(4):150-8.
13. Pollock G, Minuk GY. Diagnostic considerations for cholestatic liver disease. Journal of Gastroenterology and Hepatology. 2017;32(7):1303-9.
14. Erlichman J, Loomes KM, Rand EB. Causes of cholestasis in neonates and young infants. Dostupno na: https://www uptodate com. 2016.
15. Feldman AG, Sokol RJ. Neonatal Cholestasis: Updates on Diagnostics, Therapeutics, and Prevention. NeoReviews. 2021;22(12):e819-e36.
16. McKiernan PJ. Neonatal cholestasis. Seminars in neonatology : SN. 2002;7(2):153-65.
17. Feldman AG, Sokol RJ. Neonatal cholestasis. NeoReviews. 2013;14(2):e63-e73.
18. Betalli P, Davenport M. Biliary atresia and other congenital disorders of the extrahepatic biliary tree. Pediatric Hepatology and Liver Transplantation. 2019:129-44.
19. Esmaili J, Izadyar S, Karegar I, Gholamrezanezhad A. Biliary atresia in infants with prolonged cholestatic jaundice: diagnostic accuracy of hepatobiliary scintigraphy. Abdominal imaging. 2007;32:243-7.
20. Harpavat S, Garcia-Prats JA, Anaya C, Brandt ML, Lupo PJ, Finegold MJ, et al. Diagnostic yield of newborn screening for biliary atresia using direct or conjugated bilirubin measurements. Jama. 2020;323(12):1141-50.
21. Wada H, Muraji T, Yokoi A, Okamoto T, Sato S, Takamizawa S, et al. Insignificant seasonal and geographical variation in incidence of biliary atresia in Japan: a regional survey of over 20 years. Journal of pediatric surgery. 2007;42(12):2090-2.
22. Fabris L, Fiorotto R, Spirli C, Cadamuro M, Mariotti V, Perugorria MJ, et al. Pathobiology of inherited biliary diseases: a roadmap to understand acquired liver diseases. Nature Reviews Gastroenterology & Hepatology. 2019;16(8):497-511.
23. El-Guindi MA-S, Sira MM, Sira AM, Salem TA-H, El-Abd OL, Konsowa HA-S, et al. Design and validation of a diagnostic score for biliary atresia. Journal of hepatology. 2014;61(1):116-23.
24. Delemos AS, Friedman LS. Systemic causes of cholestasis. Clinics in liver disease. 2013;17(2):301-17.
25. Guthrie G, Burrin D. Impact of parenteral lipid emulsion components on cholestatic liver disease in neonates. Nutrients. 2021;13(2):508.
26. Serinet M-O, Wildhaber BE, Broue P, Lachaux A, Sarles J, Jacquemin E, et al. Impact of age at Kasai operation on its results in late childhood and adolescence: a rational basis for biliary atresia screening. Pediatrics. 2009;123(5):1280-6.
27. Suchy FJ. Neonatal cholestasis. Pediatrics in review. 2004;25(11):388-96.
28. Lane E, Murray KF. Neonatal cholestasis. Pediatric Clinics. 2017;64(3):621-39.
29. Venigalla S, Gourley GR, editors. Neonatal cholestasis. Seminars in perinatology; 2004: Elsevier.
30. Suchy FJ, Balistreri WF, Heubi JE, Searcy JE, Levin RS. Physiologic cholestasis: elevation of the primary serum bile acid concentrations in normal infants. Gastroenterology. 1981;80(5 pt 1):1037-41.
31. Suchy FJ. Neonatal cholestasis. Pediatrics in review. 2004;25(11):388-96.
32. Fawaz R, Baumann U, Ekong U, Fischler B, Hadzic N, Mack CL, et al. Guideline for the evaluation of cholestatic jaundice in infants: joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. Journal of pediatric gastroenterology and nutrition. 2017;64(1):154-68.
33. Fawaz R, Baumann U, Ekong U, Fischler B, Hadzic N, Mack CL, et al. Guideline for the Evaluation of Cholestatic Jaundice in Infants: Joint Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. Journal of pediatric gastroenterology and nutrition. 2017;64(1):154-68.
34. Ghazy RM, Khedr MA. Neonatal cholestasis: recent insights. Egyptian Pediatric Association Gazette. 2019;67(1):9.
35. Pandita A, Gupta V, Gupta G. Neonatal Cholestasis: A Pandora's Box. Clinical medicine insights Pediatrics. 2018;12:1179556518805412.
36. Suchy FJ, Balistreri WF, Heubi JE, Searcy JE, Levin RS. Physiologic cholestasis: elevation of the primary serum bile acid concentrations in normal infants. Gastroenterology. 1981;80(5):1037-41.
37. Harpavat S, Finegold MJ, Karpen SJ. Patients with biliary atresia have elevated direct/conjugated bilirubin levels shortly after birth. Pediatrics. 2011;128(6):e1428-33.
38. Ghazy RM, Khedr MA. Neonatal cholestasis: recent insights. Egyptian Pediatric Association Gazette. 2019;67:1-14.
39. Landing BH, Wells TR, Ramicone E. Time course of the intrahepatic lesion of extrahepatic biliary atresia: a morphometric study. Pediatric pathology. 1985;4(3-4):309-19.
40. Götze T, Blessing H, Grillhösl C, Gerner P, Hoerning A. Neonatal cholestasis–differential diagnoses, current diagnostic procedures, and treatment. Frontiers in pediatrics. 2015;3:43.
41. De Bruyne R, Van Biervliet S, Vande Velde S, Van Winckel M. Clinical practice: neonatal cholestasis. European journal of pediatrics. 2011;170:279-84.
42. Feldman AG, Sokol RJ, editors. Recent developments in diagnostics and treatment of neonatal cholestasis. Seminars in pediatric surgery; 2020: Elsevier.
43. Dani C, Pratesi S, Raimondi F, Romagnoli C, Neonatology TFfHotISo. Italian guidelines for the management and treatment of neonatal cholestasis. Italian Journal of pediatrics. 2015;41:1-12.
44. Feranchak AP, Sokol RJ, Suchy F. Medical and nutritional management of cholestasis in infants and children. Liver disease in children. 2007;3:190-231.
45. Best C. Management of neonatal cholestasis. Clinical Practice. 2009;6(1):75.
46. Balistreri WF. Neonatal cholestasis. The Journal of pediatrics. 1985;106(2):171-84.
47. Sokol RJ, Shepherd RW, Superina R, Bezerra JA, Robuck P, Hoofnagle JH. Screening and outcomes in biliary atresia: summary of a National Institutes of Health workshop. Hepatology. 2007;46(2):566-81.
48. Bhatia V, Bavdekar A, Pediatrics SKYftPGCoIAo. Management of acute liver failure in infants and children: consensus statement of the pediatric gastroenterology chapter, Indian academy of pediatrics. Indian pediatrics. 2013;50:477-82.
49. Bijl E, Bharwani K, Houwen R, De Man R. The long-term outcome of the Kasai operation in patients with biliary atresia: a systematic review. Neth J Med. 2013;71(4):170-3.
50. Zerbini M, Gallucci S, Maezono R, Ueno C, Porta G, Maksoud JG, et al. Liver biopsy in neonatal cholestasis: a review on statistical grounds. Modern Pathology: an Official Journal of the United States and Canadian Academy of Pathology, Inc. 1997;10(8):793-9.
| Files | ||
| Issue | Vol 7, No 1 (2024) | |
| Section | Review Article | |
| DOI | https://doi.org/10.18502/igj.v7i1.17517 | |
| Keywords | ||
| Bile Metabolism Disorders Infant Liver Disease Neonatal Cholestasis Physiological Jaundice | ||
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How to Cite
1.
Mohamadi S, Mohammadi S, Kadivar M. Neonatal Cholestasis: Definition, Clinical Manifestation and Management; A Mini Review. Immunol Genet J. 2024;7(1):24-29.
