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  • Brief Communication
  • Published:

Impact of congenital heart disease and prematurity on brain injury from a national registry

Journal of Perinatology volume 45, pages 1005–1008 (2025)Cite this article

Subjects

There is a high prevalence of brain injury in term neonates with congenital heart disease (CHD) [1]. Preterm birth is associated with increased risk of neurological morbidities, specifically intraventricular hemorrhages (IVH), post-hemorrhagic hydrocephalus (PHH), and periventricular leukomalacia (PVL) [2]. While overall morbidity and mortality rates for neonates with CHD have declined over the past decade [3], there is less evidence about the influence of preterm birth on CHD and their combined impact on the development of IVH and PHH [4]. Furthermore, most of the current literature is from single institutions with a wide range of reported IVH rates in preterm infants with CHD. Accordingly, the objective of this brief communication is to define the incidence of IVH and PHH in premature infants with CHD from large national contemporary population-based dataset.

We performed a 12-year (2010–2022) multicenter descriptive cohort study of neonates with CHD in the Children’s Hospitals Neonatal Consortium (CHNC), a collaborative of 49 Level IV neonatal intensive care units in the United States and Canada. The CHNC prospectively collects data on all infants, including premature infants with CHD, admitted to the neonatal intensive care unit of participating CHNC centers. The patient-level data for 36,048 infants with CHD who received care at a CHNC were collected by trained personnel [5]. All infants with CHD were included in the analysis. For this analysis, the primary outcomes assessed were severe IVH, defined as grade III or IV, and PHH. Cardiac lesions were classified into four subtypes: compromised systemic output (hypoplastic left heart syndrome, coarctation of the aorta, interrupted or hypoplastic aortic arch, aortic or mitral valve stenosis), sustained cyanosis (Ebstein’s anomaly, Tetralogy of Fallot, hypoplastic right heart syndrome, pulmonary artery stenosis or atresia, pulmonary or tricuspid valve stenosis), congestive heart failure (double outlet right ventricle, truncus arteriosus, transposition of the great vessels, atrioventricular canal, arterial or ventricular septal defect), and arrhythmias. For statistical analysis, Chi-square or Fisher’s Exact test were used to comapre categorical variables, while Kruskal–Wallis was used compare continuous variables. All tests were two-sided and there were no adjustments for multiple comparisons. Medians were reported as center values. The Institutional Review Board of Emory University approved this study, and all CHNC centers obtained regulatory oversight to participate in the CHNC.

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Fig. 1: Brain injury among premature infants with congenital heart disease.

References

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Acknowledgements

The authors are grateful to the infants and their families for participating in this research study. The authors would also like to acknowledge 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, as 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). A full list of all participating centers is available in the Supplemental Document.

Author information

Author notes

  1. These authors contributed equally: Giulia P. Lima, Sarah U. Morton.

Authors and Affiliations

  1. Department of Pediatrics, Harvard Medical School and Division of Newborn Medicine, Boston Children’s Hospital, Boston, MA, USA

    Giulia P. Lima, Sarah U. Morton & Philip Levy

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

    Isabella Zaniletti

  3. Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of California San Diego and Rady Children’s Hospital, San Diego, CA, USA

    Nathaly Sweeney

  4. Division of Neonatology, The Ohio State University Wexner Medical Center, Columbus, OH, USA

    Leeann Pavlek & Molly K. Ball

  5. Division of Neonatology, Emory University and Children’s Healthcare of Atlanta, Atlanta, GA, USA

    Shannon E. G. Hamrick

  6. Division of Neonatology, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA

    Sharada H. Gowda

  7. Division of Neonatology, Department of Pediatrics, Washington University School of Medicine, St. Louis Children’s Hospital, St. Louis, MO, USA

    Rakesh Rao

  8. Division of Neonatology, Department of Pediatrics, Indiana University School of Medicine, Riley Hospital for Children, Indianapolis, IN, USA

    Paulomi M. Chaudhry

  9. Children’s Healthcare of Atlanta – Egleston, Atlanta, GA, USA

    Anthony Piazza

  10. Children’s Healthcare of Atlanta – Scottish Rite, Atlanta, GA, USA

    Gregory Sysyn

  11. Dell Children’s Medical Center, Austin, TX, USA

    Ashley Lucke & Molly Pont

  12. Children’s of Alabama, Birmingham, AL, USA

    Allison Black & Carl Coghill

  13. Boston Children’s Hospital, Boston, MA, USA

    Marth Sola Visner

  14. Levine Children’s Hospital, Charlotte, NC, USA

    Eugenia Pallotto

  15. Ann & Robert H. Lurie Children’s Hospital, Chicago, IL, USA

    Karna Murthy & Gustave Falciglia

  16. Cincinnati Children’s Hospital, Cincinnati, OH, USA

    Beth Haberman

  17. Cleveland Clinic, Cleveland, OH, USA

    Ceyda Acun

  18. Nationwide Children’s Hospital, Columbus, OH, USA

    Thomas Bartman

  19. Children’s Medical Center, Dallas, TX, USA

    Sushmita Yallapragada & Lina Chalak

  20. Children’s Hospital Colorado, Denver, CO, USA

    Danielle Smith & Stephanie Bourque

  21. Children’s Hospital Michigan, Detroit, MI, USA

    Girija Natarajan

  22. Cook Children’s Healthcare System, Fort Worth, TX, USA

    Annie Chi & Yvette Johnson

  23. Connecticut Children’s Medical Center, Hartford, CT, USA

    Annmarie Gotiolo

  24. Texas Children’s Hospital, Houston, TX, USA

    Lakshmi Katarkan & Kristina Reber

  25. Riley Children’s Health, Indianapolis, IN, USA

    Rebecca Rose

  26. University of Iowa Stead Family Children’s Hospital, Iowa City, IA, USA

    Julie Lindower

  27. The Children’s Mercy Hospital, Kansas City, MO, USA

    Julie Weiner

  28. Arkansas Children’s Hospital, Little Rock, AR, USA

    Laura Carroll

  29. Los Angeles Children’s Hospital, Los Angeles, CA, USA

    Rachel Chapman

  30. American Family Children’s Hospital, Madison, WI, USA

    Nina Menda

  31. Le Bonheur Children’s Hospital, Memphis, TN, USA

    Mark Weems

  32. Children’s Minnesota Hospital, Minneapolis, MN, USA

    Ann Downey

  33. Wisconsin Children’s Hospital, Milwaukee, WI, USA

    Joanne Lagatta

  34. UCSF Benioff Children’s Hospital, Oakland, CA, USA

    Priscilla Joe

  35. Oklahoma Children’s Hospital, Oklahoma City, OK, USA

    Trent Tipple & Patricia Williams

  36. Omaha Children’s Hospital, Omaha, NE, USA

    Nicole Birge

  37. Children’s Hospital of Orange County, Orange County, CA, USA

    Michel Mikhael

  38. AdventHealth for Children, Orlando, FL, USA

    Narendra Dereddy & Rajan Wadhawan

  39. Nemours Children’s Hospital, Orlando, FL, USA

    Aaron Weiss

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

    Michael Padula

  41. St. Christopher’s Hospital for Children, Philadelphia, PA, USA

    Vilarmis Quinones

  42. Phoenix Children’s Hospital, Phoenix, AZ, USA

    Pam Griffiths

  43. Pittsburgh Children’s Hospital, Pittsburgh, PA, USA

    Toby Yanowitz

  44. Mayo Clinic Children’s Center, Rochester, MN, USA

    Ellen Bendel-Stenzel

  45. Primary Children’s Hospital, Salt Lake City, UT, USA

    Con Yee Ling

  46. Rady Children’s Hospital, San Diego, CA, USA

    Mark Speziale

  47. Seattle Children’s Hospital, Seattle, WA, USA

    Robert DiGeronimo & Elizabeth Jacobsen

  48. St. Louis Children’s Hospital, St. Louis, MO, USA

    Beverly Brozanski & Rakesh Rao

  49. Children’s Minnesota Hospital, St. Paul, MN, USA

    Ann Downey

  50. All Children’s Hospital, St, Petersburg, FL, USA

    Linda Van Marter

  51. The Hospital for Sick Children, Toronto, ON, Canada

    Kyong-Soon Lee

  52. Children’s National Hospital, Washington, DC, USA

    Billie Lou Short

  53. Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA

    Kevin Sullivan

  54. Brenner Children’s Hospital, Winston-Salem, NC, USA

    Cherrie Welch

Authors
  1. Giulia P. Lima
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  2. Sarah U. Morton
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  3. Isabella Zaniletti
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  4. Philip Levy
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  5. Nathaly Sweeney
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  6. Leeann Pavlek
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  7. Shannon E. G. Hamrick
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  8. Sharada H. Gowda
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  9. Rakesh Rao
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  10. Molly K. Ball
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  11. Paulomi M. Chaudhry
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Consortia

on behalf of the CHNC Cardiology Focus Group

  • Anthony Piazza
  • , Gregory Sysyn
  • , Ashley Lucke
  • , Molly Pont
  • , Allison Black
  • , Carl Coghill
  • , Marth Sola Visner
  • , Eugenia Pallotto
  • , Karna Murthy
  • , Gustave Falciglia
  • , Beth Haberman
  • , Ceyda Acun
  • , Thomas Bartman
  • , Sushmita Yallapragada
  • , Lina Chalak
  • , Danielle Smith
  • , Stephanie Bourque
  • , Girija Natarajan
  • , Annie Chi
  • , Yvette Johnson
  • , Annmarie Gotiolo
  • , Lakshmi Katarkan
  • , Kristina Reber
  • , Rebecca Rose
  • , Julie Lindower
  • , Julie Weiner
  • , Laura Carroll
  • , Rachel Chapman
  • , Nina Menda
  • , Mark Weems
  • , Ann Downey
  • , Joanne Lagatta
  • , Priscilla Joe
  • , Trent Tipple
  • , Patricia Williams
  • , Nicole Birge
  • , Michel Mikhael
  • , Narendra Dereddy
  • , Rajan Wadhawan
  • , Aaron Weiss
  • , Michael Padula
  • , Vilarmis Quinones
  • , Pam Griffiths
  • , Toby Yanowitz
  • , Ellen Bendel-Stenzel
  • , Con Yee Ling
  • , Mark Speziale
  • , Robert DiGeronimo
  • , Elizabeth Jacobsen
  • , Beverly Brozanski
  • , Rakesh Rao
  • , Ann Downey
  • , Linda Van Marter
  • , Kyong-Soon Lee
  • , Billie Lou Short
  • , Kevin Sullivan
  •  & Cherrie Welch

Contributions

PMC, MKB, and NS conceptualized the study. SUM, PL, LP, RR, SEGH, and SHG assisted with study design and provided expert input. IZ carried out analyses. GPL, SUM, PL and PMC drafted the initial manuscript. All authors critically reviewed and revised the manuscript for important intellectual content. All authors approved the final manuscript as submitted.

Corresponding author

Correspondence to Sarah U. Morton.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics Approval and Consent to Participate

The study was approved by the Institutional Review Board of Emory, and all CHNC centers obtained regulatory oversight to participate. All study activities were performed in accordance with the relevant guidelines and regulations. As the study was retrospective in nature and the clinical data were analyzed anonymously, no extra cost was incurred for the patients. The IRB has waived the need for informed consent.

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Lima, G.P., Morton, S.U., Zaniletti, I. et al. Impact of congenital heart disease and prematurity on brain injury from a national registry. J Perinatol 45, 1005–1008 (2025). https://doi.org/10.1038/s41372-025-02281-6

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  • DOI: https://doi.org/10.1038/s41372-025-02281-6

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