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A multicenter descriptive study of neonatal-onset urea cycle disorder patients hospitalized in level IV NICUs

Journal of Perinatology (2026)Cite this article

Subjects

Abstract

Objective

The objective of this study was to characterize the neonatal intensive care unit (NICU) course and outcomes for infants with neonatal-onset urea cycle disorders (UCDs).

Study design

Using the multicenter Children’s Hospitals Neonatal Database, a descriptive, retrospective cohort study was performed to characterize the presentation, interventions, comorbidities, and hospital outcomes for 176 patients with neonatal-onset UCDs that required level IV NICU care.

Results

The median age of presentation was 5 [3,7] days, with 167 (95%) infants requiring transfer to a level IV NICU. Renal replacement therapy was undertaken for at least 34 (20%) patients. Neurologic complications occurred most frequently, with 71 (40%) patients affected. Twenty-one (12%) infants experienced in-hospital mortality. Interventions, complications, and mortality were observed most frequently in the ornithine transcarbamylase deficiency group.

Conclusion

Neonatal-onset UCDs are associated with significant morbidity and mortality, but heterogeneity exists among the specific named UCDs.

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Fig. 1: Urea cycle disorder study cohort.

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Acknowledgement

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 appreciate Mr. John Mallett and Ms. Evelyn Werbaneth’s contribution to study design and data analysis. 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 Hospitals Neonatal Database (CHND): Atlanta, Children’s Healthcare of Atlanta—Egleston (Anthony Piazza), Atlanta, Children’s Healthcare of Atlanta—Scottish Rite (Gregory Sysyn), Austin, Dell Children’s (Ashley Lucke, Molly Pont), Birmingham, Children’s of Alabama (Allison Black, Carl Coghill), Boston Children’s Hospital (Anne Hansen), Charlotte, Levine Children’s Hospital (Eugenia Pallotto), Chicago, Ann & Robert H. Lurie Children’s Hospital (Karna Murthy, Gustave Falciglia), Cincinnati Children’s Hospital (Beth Haberman), Cleveland Clinic (Tetyana Nesterenko), Columbus, Nationwide Children’s Hospital (Thomas Bartman), Dallas, Children’s Medical Center (Sushmita Yallapragada, Lina Chalak), Denver, Children’s Hospital Colorado (Danielle Smith, Stephanie Bourque), Detroit, Children’s Hospital Michigan (Girija Natarjan),Ft. Worth, Cook Children’s Healthcare System (Annie Chi, Yvette Johnson), Hartford, Connecticut Children’s (Annmarie Gotiolo), Houston, Texas Children’s Hospital (Lakshmi Katarkan, Kristina Reber), Indianapolis, Riley Children’s Health (Rebecca Rose), Iowa City, University of Iowa Stead Family Children’s Hospital (Julie Lindower), Kansas City, The Children’s Mercy Hospital (Julie Weiner), Little Rock, Arkansas Children’s (Laura Carroll), Los Angeles Children’s Hospital (Rachel Chapman), Madison, American Family Children’s Hospital (Nina Menda), Memphis, Le Bonheur Children’s Hospital (Mark Weems), Minneapolis, Children’s Minnesota (Ann Downey), Milwaukee, Wisconsin Children’s Hospital (Joanne Lagatta), Oakland, UCSF Benioff Children’s Hospital (Priscilla Joe), Oklahoma Children’s Hospital (Trent Tipple, Patricia Williams), Omaha Children’s Hospital (Nicole Birge), Orange County, Children’s Hospital of Orange County (Michel Mikhael), Orlando, AdventHealth for Children (Narendra Dereddy, Rajan Wadhawan), Orlando, Nemours Children’s Hospital (Aaron Weiss), Philadelphia, Children’s Hospital of Philadelphia (Michael Padula), Philadelphia, St. Christopher’s Hospital for Children (Vilarmis Quinones), Phoenix Children’s Hospital (Pam Griffiths), Pittsburgh Children’s Hospital (Toby Yanowitz, Abeer Azzuqa), Rochester, MN, Mayo Clinic Children’s (Ellen Bendel-Stenzel), Salt Lake City, Primary Children’s Hospital (Con Yee Ling), San Diego, Rady Children’s Hospital (Mark Speziale), Seattle Children’s Hospital (Robert DiGeronimo, Elizabeth Jacobsen), St. Louis Children’s Hospital (Beverly Brozanski, Rakesh Rao), St Paul, Children’s Minnesota (Ann Downey), St. Petersburg, All Children’s Hospital (Linda Van Marter), Toronto, The Hospital for Sick Children (Kyong-Soon Lee), Washington, Children’s National Hospital (Billie Lou Short), Wilmington, Nemours/Alfred I. duPont Hospital for Children (Kevin Sullivan), Winston-Salem, Brenner Children’s Hospital (Cherrie Welch).

Author information

Authors and Affiliations

  1. Mayo Clinic, Rochester, MN, USA

    Whitney S. Thompson, Ellen M. Bendel-Stenzel & Queenie K. G. Tan

  2. Children’s Hospitals Neonatal Consortium, Dover, DE, USA

    Isabella Zaniletti, Theresa R. Grover, Karna Murthy & Michael A. Padula

  3. University of Colorado School of Medicine and Children’s Hospital Colorado, Aurora, CO, USA

    Theresa R. Grover

  4. Feinberg School of Medicine, Northwestern University, and Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, USA

    Karna Murthy

  5. Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Michael A. Padula

  6. Indiana University School of Medicine and Riley Children’s Hospital, Indianapolis, IN, USA

    Kristen R. Suhrie

Authors
  1. Whitney S. Thompson
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  2. Ellen M. Bendel-Stenzel
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  8. Kristen R. Suhrie
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Contributions

Whitney Thompson conceptualized and designed the study, performed data analysis, drafted the initial manuscript, and critically reviewed and revised the manuscript. Ellen Bendel-Stenzel and Kristen Suhrie conceptualized and designed the study, performed data analysis, and critically reviewed and revised the manuscript. Isabella Zaniletti contributed to the design of the study, collected data, performed the initial statistical analyses, and critically reviewed and revised the manuscript. Theresa Grover, Karna Murthy, and Michael Padula contributed to the design of the study, performed data analysis, and critically reviewed and revised the manuscript. Queenie Tan performed data analysis and critically reviewed and revised the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Whitney S. Thompson.

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Competing interests

KRS has received honoraria from Illumina for a speaking engagement. WST serves on the Clinical Advisory Board for Inflection Medicine and is engaged in a know-how agreement with the company. The other authors have no competing interests to disclose.

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Thompson, W.S., Bendel-Stenzel, E.M., Zaniletti, I. et al. A multicenter descriptive study of neonatal-onset urea cycle disorder patients hospitalized in level IV NICUs. J Perinatol (2026). https://doi.org/10.1038/s41372-025-02557-x

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