Risk of carcinomas among children and adolescents with birth defects.

Background: Birth defects are associated with childhood cancer, but little is known regarding pediatric carcinomas, a group of especially rare tumors.

Methods: We used Cox proportional hazards regression to estimate the hazard ratio (HR) and 95 % confidence interval (CI) for any carcinoma, as well as thyroid, hepatocellular, and renal carcinoma specifically, up to 18 years of age among children with major, non-syndromic anomalies or chromosomal/genetic syndromes, relative to unaffected children.

Results: Our registry-linkage study included nine states and 21,933,476 children between 1990 and 2018: 641,827 with non-syndromic anomalies, and 49,619 with syndromes. Carcinomas were diagnosed in 833 children, including 35 with non-syndromic anomalies and eight with syndromes. The hazard of carcinoma was increased both among children with non-syndromic anomalies (HR: 1.7, CI: 1.2-2.4; N = 35) and syndromes (HR: 4.7, CI: 2.3-9.5; N = 7). Hepatocellular carcinoma was associated with non-syndromic anomalies (HR: 4.6, CI: 2.2-9.7; N = 8) and syndromes (HR: 8.0, CI: 1.1-58.1; N < 5). The hazard of renal carcinoma was markedly increased in children with tuberous sclerosis (HR 59.6, CI: 23.7-149.5; N = 5), a known cause of renal cancer. Thyroid carcinoma was not associated with non-syndromic anomalies or syndromes.

Conclusion: Birth defects are associated with hepatocellular and renal carcinoma in children.