Cesarean Section Is Associated with an Increased Risk of Acute Lymphoblastic Leukemia and Hepatoblastoma in Children from Minnesota.

Background In recent decades, Cesarean section (C-section) rates have increased. C-section is hypothesized to negatively impact the developing immune system by altering activation of the hypothalamic-pituitary-adrenal axis and the infant microbiome, among other mechanisms, thereby potentially modulating childhood cancer risk. Methods Using linked birth and cancer registry data from Minnesota (1976-2014), we included individuals aged 0-14 at diagnosis with one of 19 cancers. Cases and controls were frequency matched by birth year. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (95% CI) as the measure of association between C-section and cancer. We assessed sex-C-section interactions for each cancer and conducted stratified analyses in ALL for birth year, age at diagnosis, and maternal race. Results There were 3,166 cases and 20,589 controls. One third (n=1,174) of controls born during 2004-2014 were delivered via C-section compared to 42.2% of cases (n=285). C-section was associated with ALL (n=819) (OR: 1.20; 95% CI: 1.01-1.43) and hepatoblastoma (n=50) (OR: 1.89; 95% CI: 1.03-3.48), particularly among females (ALL OR: 1.34; 95% CI: 1.04-1.72; hepatoblastoma OR: 3.87; 95% CI: 1.30-11.57). The risk of ALL was highest during 2005-2014 (OR: 1.62; 95% CI: 1.11-2.34) and among children aged 1-5 years (OR: 1.28; 95% CI: 1.02-1.61). Conclusions C-section was associated with and increased risk of ALL and hepatoblastoma. Impact These associations require investigation to determine causality and rule out confounding by indication or reverse causality. The mechanisms underlying these associations may depend on neonatal immune system processes altered during C-section deliveries.