Mode of delivery and the risk of lymphoblastic leukemia during childhood-A Swedish population-based cohort study

Cesarean section (CS) rates have been increasing beyond medically warranted thresholds, despite potential long-term adverse outcomes. Previous research on CS delivery and childhood leukemia is conflicting but suggests an increased acute lymphoblastic leukemia (ALL) risk in children delivered by planned CS. It has been suggested that maternal and pregnancy conditions predisposing to pregnancy complications might confound such an association; therefore, we aimed to elucidate the relationship between delivery mode and ALL in Swedish children. To this end, we studied all children born in Sweden between 1982-1989 and 1999-2014, when comprehensive information on delivery mode was available (n = 2,442,330). Pregnancy conditions, delivery mode, and childhood ALL diagnoses (<20 years) were retrieved from nationwide registers. Cox proportional hazards regression was used to assess the association between delivery mode and childhood ALL, adjusting for maternal and pregnancy conditions. We observed an increased ALL risk among children delivered by planned CS (HR = 1.21, 95% CI 0.96-1.54), driven by B-cell precursor ALL (HR = 1.29, 95% CI 1.01-1.67). The associations were concentrated among boys and at peak ages of ALL incidence (≤5 years) and persisted after accounting for potential confounders, including maternal and perinatal factors. Unplanned CS was not associated with increased risk of childhood ALL. Our nationwide study supports an association between planned CS and an increased B-cell precursor ALL risk in Swedish children, irrespective of maternal and pregnancy conditions. Possible underlying mechanisms, such as lack of exposure to maternal vaginal microbiota or decreased stress hormones at birth, require further exploration.