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Cholestasis is associated with a higher rate of complications in both medical and surgical necrotizing enterocolitis

Journal of Perinatology volume 44, pages 100–107 (2024)Cite this article

Subjects

Abstract

Objective

To evaluate the relationship between cholestasis and outcomes in medical and surgical necrotizing enterocolitis (NEC).

Study design

A retrospective analysis of prospectively collected data from 1472 infants with NEC [455 medical (mNEC) and 1017 surgical (sNEC)] from the Children’s Hospital Neonatal Database.

Results

The prevalence of cholestasis was lower in mNEC versus sNEC (38.2% vs 70.1%, p < 0.001). In both groups, cholestasis was associated with lower birth gestational age [mNEC: OR 0.79 (95% CI 0.68–0.92); sNEC: OR 0.86 (95% CI 0.79–0.95)] and increased days of parenteral nutrition [mNEC: OR 1.08 (95% CI 1.04–1.13); sNEC: OR 1.01 (95% CI 1.01–1.02)]. For both groups, the highest direct bilirubin was associated with the composite outcome mortality or length of stay >75th percentile [mNEC: OR 1.21 (95% CI 1.06–1.38); sNEC: OR 1.06 (95% CI 1.03–1.09)].

Conclusion

Cholestasis with both medical NEC and surgical NEC is associated with adverse patient outcomes including increased mortality or extreme length of stay.

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Fig. 1: Gestational age distribution by NEC type and cholestasis diagnosis.

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Data availability

All data relevant to the study is included in the article. Requests for additional material can be made to Pritha.nayak@utsouthwestern.edu.

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Acknowledgements

Beverly Brozanski, Jacquelyn Evans, Theresa Grover, Karna Murthy, Michael Padula, Eugenia Pallotto, Anthony Piazza, Kristina Reber and Billie Short and ex-officio David Durand, Francine Dykes, Jeanette Asselin), are executive members of the Children’s Hospitals Neonatal Consortium, Inc., who developed and manage the CHND (thechnc.org). For more information, please contact: exec@thechnc.org. We are indebted to the following CHNC participating institutions that serve the infants and their families; these institutions (and their site sponsors) also have invested in and continue to participate in the Children’s Hospital’s Neonatal Database (CHND): 1. Atlanta, Children’s Healthcare of Atlanta – Egleston (Anthony Piazza) 2. Atlanta, Children’s Healthcare of Atlanta - Scottish Rite (Gregory Sysyn) 3. Austin, Dell Children’s (Ashley Lucke, Molly Pont) 4. Birmingham, Children’s of Alabama (Allison Black, Carl Coghill) 5. Boston Children’s Hospital (Anne Hansen) 6. Charlotte, Levine Children’s Hospital (Eugenia Pallotto) 7. Chicago, Ann & Robert H. Lurie Children’s Hospital (Karna Murthy, Gustave Falciglia) 8. Cincinnati Children’s Hospital (Beth Haberman) 9. Cleveland Clinic (Tetyana Nesterenko) 10. Columbus, Nationwide Children’s Hospital (Thomas Bartman) 11. Dallas, Children’s Medical Center (Sushmita Yallapragada, Lina Chalak) 12. Denver, Children’s Hospital Colorado (Danielle Smith, Stephanie Bourque) 13. Detroit, Children’s Hospital Michigan (Girija Natarjan) 14. Ft. Worth, Cook Children’s Healthcare System (Annie Chi, Yvette Johnson) 15. Hartford, Connecticut Children’s (Annmarie Gotiolo) 16. Houston, Texas Children’s Hospital (Lakshmi Katarkan, Kristina Reber) 17. Indianapolis, Riley Children’s Health (Rebecca Rose) 18. Iowa City, University of Iowa Stead Family Children’s Hospital (Julie Lindower) 19. Kansas City, The Children’s Mercy Hospital (Julie Weiner) 20. Little Rock, Arkansas Children’s (Laura Carroll) 21. Los Angeles Children’s Hospital (Rachel Chapman) 22. Madison, American Family Children’s Hospital (Nina Menda) 23. Memphis, Le Bonheur Children’s Hospital (Mark Weems) 24. Minneapolis, Children’s Minnesota (Ann Downey) 25. Milwaukee, Wisconsin Children’s Hospital (Joanne Lagatta) 26. Oakland, UCSF Benioff Children’s Hospital (Priscilla Joe) 27. Oklahoma Children’s Hospital (Trent Tipple, Patricia Williams) 28. Omaha Children’s Hospital (Nicole Birge) 29. Orange County, Children’s Hospital of Orange County (Michel Mikhael) 30. Orlando, AdventHealth for Children (Narendra Dereddy, Rajan Wadhawan) 31. Orlando, Nemours Children’s Hospital (Aaron Weiss) 32. Philadelphia, Children’s Hospital of Philadelphia (Michael Padula) 33. Philadelphia, St. Christopher’s Hospital for Children (Vilarmis Quinones) 34. Phoenix Children’s Hospital (Pam Griffiths) 35. Pittsburgh Children’s Hospital (Toby Yanowitz) 36. Rochester, MN, Mayo Clinic Children’s (Ellen Bendel-Stenzel) 37. Salt Lake City, Primary Children’s Hospital (Con Yee Ling) 38. San Diego, Rady Children’s Hospital (Mark Speziale) 39. Seattle Children’s Hospital (Robert DiGeronimo, Elizabeth Jacobsen) 40. St. Louis Children’s Hospital (Beverly Brozanski, Rakesh Rao) 41. St Paul, Children’s Minnesota (Ann Downey) 42. St. Petersburg, All Children’s Hospital (Linda Van Marter) 43. Toronto, The Hospital for Sick Children (Kyong-Soon Lee) 44. Washington, Children’s National Hospital (Billie Lou Short) 45. Wilmington, Nemours/Alfred I. duPont Hospital for Children (Kevin Sullivan) 46. Winston-Salem, Brenner Children’s Hospital (Cherrie Welch).

Author information

Author notes

  1. These authors contributed equally: Sujir Pritha Nayak, Katie A. Huff.

  2. A full list of members and their affiliations appears in the Supplementary Information.

Authors and Affiliations

  1. University of Texas Southwestern Medical Center, Dallas, TX, USA

    Sujir Pritha Nayak

  2. Indiana University School of Medicine, Riley Hospital for Children, Indianapolis, IN, USA

    Katie A. Huff & Troy A. Markel

  3. Children’s Hospital Association, Lenexa, KS, USA

    Isabella Zaniletti

  4. Children’s Hospitals Orange County, Orange, CA, USA

    Irfan Ahmad

  5. University of Washington School of Medicine, Seattle Children’s Hospital, Seattle, WA, USA

    Robert DiGeronimo

  6. Baylor College of Medicine, Texas Children’s Hospital, Houston, TX, USA

    Amy Hair, Kristina Reber & Muralidhar H. Premkumar

  7. Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Jae Kim

  8. Emory University School of Medicine, Atlanta, GA, USA

    Anthony Piazza & Jessica Roberts

  9. Children’s Mercy Kansas City, Kansas City, MO, USA

    Jotishna Sharma

  10. Nemours Children’s Hospital, Wilmington, DE, USA

    Kevin Sullivan

  11. University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Toby Yanowitz

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  1. Sujir Pritha Nayak
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Consortia

Children’s Hospitals Neonatal Consortium Necrotizing Enterocolitis Focus Group

  • Sujir Pritha Nayak
  • , Katie A. Huff
  • , Isabella Zaniletti
  • , Irfan Ahmad
  • , Robert DiGeronimo
  • , Amy Hair
  • , Jae Kim
  • , Troy A. Markel
  • , Anthony Piazza
  • , Kristina Reber
  • , Jessica Roberts
  • , Jotishna Sharma
  • , Kevin Sullivan
  • , Muralidhar H. Premkumar
  •  & Toby Yanowitz

Contributions

SPN, KAH, MP, and TY contributed to the conception and design of the study. All authors contributed to the data acquisition and provided critical input during the Children’s Hospitals Neonatal Consortium NEC focus group meetings. IZ conducted data analysis. SPN and KAH contributed equally to drafting the manuscript. MP and TY helped to critically draft and revise the manuscript. All authors helped revise the manuscript and have approved the final version.

Corresponding author

Correspondence to Sujir Pritha Nayak.

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Competing interests

The authors declare no competing interests.

Compliance with ethical standards

IRB approval was obtained at each participating site prior to entering data into CHND. For analysis of de-identified data the Stanley Manne Research Center (2011-14673) reviewed and approved this work. The study was performed in accordance with the Declaration of Helsinki.

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Nayak, S.P., Huff, K.A., Zaniletti, I. et al. Cholestasis is associated with a higher rate of complications in both medical and surgical necrotizing enterocolitis. J Perinatol 44, 100–107 (2024). https://doi.org/10.1038/s41372-023-01787-1

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