Co-occurrence of congenital anomalies and childhood brain tumors in 22 million live births

Thanh T Hoang^{1

2

3}, Jeremy M Schraw^{1

2

3}, Charles Shumate⁴, Tania A Desrosiers⁵, Wendy N Nembhard⁶, Mahsa Yazdy⁷, Eirini Nestoridi⁷, Amanda E Janitz⁸, Russell S Kirby⁹, Jason L Salemi⁹, Jean Paul Tanner⁹, Tiffany M Chambers^{1

2}, Michael D Taylor^{1

2

3}, Chad D Huff¹⁰, Sharon E Plon^{1

2

3

11

12}, Philip J Lupo^{1

2

3}, Michael E Scheurer^{1

2

3}

Affiliations

¹ Department of Pediatrics, Division of Hematology and Oncology, Baylor College of Medicine, Houston, Texas, USA.
² Texas Children's Cancer and Hematology Center, Texas Children's Hospital, Houston, Texas, USA.
³ The Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas, USA.
⁴ Birth Defects Epidemiology and Surveillance Branch, Texas Department of State Health Services, Austin, Texas, USA.
⁵ Department of Epidemiology, Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
⁶ Department of Epidemiology, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences and Arkansas Center for Birth Defects Research and Prevention, Little Rock, Arkansas, USA.
⁷ Massachusetts Center for Birth Defects Research and Prevention, Division for Surveillance, Research, and Promotion of Perinatal Health, Massachusetts Department of Public Health, Boston, Massachusetts, USA.
⁸ Department of Biostatistics and Epidemiology, Hudson College of Public Health, University of Oklahoma Health Sciences, Oklahoma City, Oklahoma, USA.
⁹ Chiles Center, College of Public Health, University of South Florida, Tampa, Florida, USA.
¹⁰ Division of Cancer Prevention and Population Sciences, Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
¹¹ Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.
¹² Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.

PMID: 40138258
PMCID: PMC12417818 (available on 2026-03-26)
DOI: 10.1093/neuonc/noaf087

Co-occurrence of congenital anomalies and childhood brain tumors in 22 million live births

Thanh T Hoang et al. Neuro Oncol. 2025.

. 2025 Sep 8;27(7):1910-1922.

doi: 10.1093/neuonc/noaf087.

Authors

Affiliations

¹ Department of Pediatrics, Division of Hematology and Oncology, Baylor College of Medicine, Houston, Texas, USA.
² Texas Children's Cancer and Hematology Center, Texas Children's Hospital, Houston, Texas, USA.
³ The Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas, USA.
⁴ Birth Defects Epidemiology and Surveillance Branch, Texas Department of State Health Services, Austin, Texas, USA.
⁵ Department of Epidemiology, Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
⁶ Department of Epidemiology, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences and Arkansas Center for Birth Defects Research and Prevention, Little Rock, Arkansas, USA.
⁷ Massachusetts Center for Birth Defects Research and Prevention, Division for Surveillance, Research, and Promotion of Perinatal Health, Massachusetts Department of Public Health, Boston, Massachusetts, USA.
⁸ Department of Biostatistics and Epidemiology, Hudson College of Public Health, University of Oklahoma Health Sciences, Oklahoma City, Oklahoma, USA.
⁹ Chiles Center, College of Public Health, University of South Florida, Tampa, Florida, USA.
¹⁰ Division of Cancer Prevention and Population Sciences, Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
¹¹ Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.
¹² Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.

PMID: 40138258
PMCID: PMC12417818 (available on 2026-03-26)
DOI: 10.1093/neuonc/noaf087

Abstract

Background: Children born with a congenital anomaly have a higher risk of developing a brain tumor during childhood or adolescence, but the co-occurrence between specific types of congenital anomalies and specific types of childhood brain tumors (CBTs) is not well described. This study characterized the associations between specific congenital anomalies and CBTs.

Methods: We leveraged a population-based registry linkage study of births (1990-2018), congenital anomalies, and cancer from 9 states (n = 22,599,099 births). Congenital anomalies were classified as major structural without a known chromosomal or genetic syndrome, chromosomal, neurofibromatosis, and/or tuberous sclerosis complex. CBT classification was based on the International Classification of Childhood Cancer for children diagnosed < 20 years. Cox regression analyses were conducted separately by congenital anomaly for anomaly-CBT combinations with at least 5 co-occurring cases. We conducted analyses for any CBT and separately for astrocytoma, atypical teratoid/rhabdoid tumor, ependymoma, medulloblastoma, mixed and unspecified gliomas, and primitive neuroectodermal tumors.

Results: There were 6,247 children diagnosed with a CBT. Having any major structural anomaly was associated with risk of any CBT and across all subgroups (aHR range: 1.48-3.69) except ependymoma, particularly among children diagnosed with a tumor by 1 year of age. Of the 66 anomaly-CBT combinations analyzed, 42 were significant (P < .05), including 25 in an earlier version of this study and 16 novel associations (aHR range: 1.46-525). Anomaly-CBT associations also differed by astrocytoma histology.

Conclusions: We observed consistent evidence that having a structural congenital anomaly increases risk of developing a CBT, particularly in infancy, which may provide insights into etiology.

Keywords: birth defects; childhood cancer; congenital malformations; epidemiology; pediatric brain tumor.

© The Author(s) 2025. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.

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Conflict of interest statement

None declared.

References

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Co-occurrence of congenital anomalies and childhood brain tumors in 22 million live births

Affiliations

Co-occurrence of congenital anomalies and childhood brain tumors in 22 million live births

Authors

Affiliations

Abstract

Conflict of interest statement

References

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Research Materials