Language

English

Publication Date

8-1-2026

Journal

Pediatric Blood & Cancer

DOI

10.1002/1545-5017.70415

PMID

42170858

PMCID

PMC13629186

PubMedCentral® Posted Date

10-2-2026

PubMedCentral® Full Text Version

Author MSS

Abstract

Background: Pediatric sarcomas are a heterogeneous group of tumors that contribute disproportionately to cancer mortality in children. Although congenital anomalies are among the strongest known risk factors for childhood cancer, the risk of specific sarcoma subtypes among affected individuals has not yet been thoroughly evaluated.

Procedure: We obtained data on maternal and perinatal characteristics, congenital anomalies, and pediatric sarcoma diagnoses for all live births in nine states. We used Cox proportional hazards regression to estimate the hazard ratio (HR) and 95% confidence interval (CI) of sarcoma (overall and by subtype) among children with non-syndromic congenital anomalies. We considered all non-syndromic anomalies collectively, and when sample size allowed, we also evaluated specific anomaly-sarcoma associations.

Results: We evaluated 21,933,884 children, including 641,770 (2.9%) with major non-syndromic congenital anomalies. Compared to children without a congenital anomaly, children with a non-syndromic anomaly had a two-fold higher hazard for any soft tissue sarcoma (95% CI: 1.7-2.5), including rhabdomyosarcoma (HR 2.2, 95% CI: 1.7-3.0) and embryonal rhabdomyosarcoma (HR 2.5, 95% CI: 1.8-3.6), as well as non-rhabdomyosarcoma soft tissue sarcoma (HR 1.8, 95% CI: 1.3-2.5). The hazard of embryonal rhabdomyosarcoma was markedly increased in children with central nervous system anomalies (HR 7.9, 95% CI: 3.9-15.9), obstructive genitourinary defects (HR 4.6, 95% CI: 2.2-9.7), and limb reduction deformities (HR 3.8, 95% CI: 1.6-9.3).

Conclusions: Children with non-syndromic congenital anomalies are at increased risk of sarcomas, especially soft tissue sarcomas. Future studies should clarify shared developmental pathways and evaluate implications for sarcoma risk prediction and surveillance.

Keywords

Registries, Information Storage and Retrieval, Sarcoma, Congenital Abnormalities, United States, Proportional Hazards Models, Humans, Male, Female, Infant, Newborn, Infant, Child, Preschool, Child, Risk Factors

Published Open-Access

yes

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