Mode of Delivery, Birth Characteristics and Early-Onset Non-Hodgkin Lymphoma in a Population-Based Case-Control Study.

Background: The etiology of non-Hodgkin lymphoma (NHL) in children, adolescents, and young adults (AYA) is not well-understood. Methods: We evaluated potential associations between mode of delivery, birth characteristics and NHL risk in a population-based case-control study, which included 3,064 cases of NHL (490 with Burkitt lymphoma, 981 with diffuse large B-cell lymphoma [DLBCL], and 978 with T-cell NHL) diagnosed at the age of 0-37 years in California during 1988-2015 and 153,200 controls frequency-matched on year of birth. Odds ratios (OR) and 95% confidence intervals (CI) were estimated from an unconditional multivariable logistic regression model that included year of birth and birth characteristics. Results: Individuals born via cesarean section had a decreased risk of pediatric Burkitt lymphoma (age 0-14 years; OR=0.71, 95% CI: 0.51-0.99) and pediatric T-cell NHL (OR=0.73, 95% CI: 0.55-0.97) compared to those born vaginally. Having a birth order of 2nd (OR=0.73, 95% CI: 0.57-0.93) or 3rd or higher (OR=0.76, 95% CI: 0.58-0.99) was associated with a lower risk of pediatric T-cell NHL compared to first-borns. AYA (age 15-37 years) with a heavier birthweight had an elevated risk of DLBCL (OR for each kg = 1.16, 95% CI: 1.00-1.35). Associations between other birth characteristics including plurality, maternal age, maternal education, and NHL risk also exhibited variations across subgroups based on age of diagnosis and histologic subtype. Conclusions: These findings support a role of mode of delivery and birth characteristics in the etiology of early-onset NHL. Impact: This study underscores the etiological heterogeneity of early-onset NHL.