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 and in 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 to 37 years in California during 1988 to 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 with those born vaginally. Having a birth order of second (OR = 0.73, 95% CI: 0.57-0.93) or third or higher (OR = 0.76, 95% CI: 0.58-0.99) was associated with a lower risk of pediatric T-cell NHL compared with 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 etiologic heterogeneity of early-onset NHL.