IMPORTANCE Birth defects affect approximately 1 in 33 children. Some birth defects are known to be strongly associated with childhood cancer (eg, trisomy 21 and acute leukemia). However, comprehensive evaluations of childhood cancer risk in those with birth defects have been limited in previous studies by insufficient sample sizes. OBJECTIVES To identify specific birth defect-childhood cancer (BD-CC) associations and characterize cancer risk in children by increasing number of nonchromosomal birth defects. DESIGN, SETTING, AND PARTICIPANTS This multistate, population-based registry linkage study pooled statewide data on births, birth defects, and cancer from Texas,

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Background The Childhood Cancer Research Network (CCRN) was established by the Children's Oncology Group (COG) as a resource for epidemiologic studies of childhood cancer. The objective of this study was to evaluate the representativeness of CCRN and identify factors associated with enrollment. Method The number of US childhood patients with cancer diagnosed <20 years of age enrolled in CCRN (2008‐2015) was compared to expected counts, calculated from Surveillance, Epidemiology, and End Results incidence rates and US Census population estimates. Observed‐to‐expected ratios and corresponding 95% confidence intervals (CI) were estimated across sex, race, diagnosis age, calendar year, and cancer diagnosis groups. Multivariable linear regression models were generated to evaluate the association between open COG phase 3 therapeutic trials and CCRN enrollment rates. Result The 43,110 cases enrolled in CCRN represented 36% of the expected childhood cancers diagnosed from 2008 to 2015 (N = 120,118). CCRN enrollment ratios [95% CI] were highest among males (0.38 [95% CI, 0.37‐0.38]), non‐Hispanics (0.35 [95% CI, 0.35‐0.36]), and those diagnosed from 1 to 4 years of age (0.50 [95% CI, 0.50‐51]). Enrollment ratios varied by diagnosis group, with leukemia, myeloproliferative diseases, myelodysplastic diseases (0.55 [95% CI, 0.54‐0.55]), and renal tumors (0.55 [95% CI, 0.53‐0.58]) having the highest enrollment. After adjusting for year of diagnosis and cancer diagnosis, there was a 3.1% [95% CI, 0.6‐5.6%] increase in CCRN enrollment during windows of open COG therapeutic trials. Conclusions Despite enrolling only 36% of newly diagnosed cases, CCRN remains a valuable resource for investigators conducting childhood cancer etiology and survivorship research. The results of this study may inform efforts to improve enrollment on current and future COG nontherapeutic registry protocols.