Children born by planned cesarean section had a higher risk of developing B-cell precursor acute lymphoblastic leukemia in childhood compared with those born by vaginal delivery, according to a large Swedish cohort study of 2,429,405 births.
Researchers analyzed data from children born in Sweden during two periods—1982 to 1989 and 1999 to 2015—when comprehensive delivery mode data were available. Using national registries, they tracked delivery method and cancer outcomes through age 20. Among the children studied, 1,495 developed leukemia, including 1,183 cases of acute lymphoblastic leukemia. Of these, 952 were B-cell precursor acute lymphoblastic leukemia (ALL).
Planned cesarean delivery was associated with an increased risk of B-cell precursor ALL, while the association with overall ALL did not reach statistical significance. Children born via planned cesarean section (CS) had a hazard ratio (HR) of 1.21 (95% confidence interval [CI], 0.96–1.54) for ALL and 1.29 (95% CI, 1.01–1.67) for B-cell precursor ALL compared with those born vaginally. These estimates remained elevated after adjustment for maternal age, diabetes, preeclampsia, infections, and perinatal factors including birth weight, birth defects, and sex.
The association appeared strongest among children diagnosed with leukemia at ages 0 to 5 years and among boys, although these subgroup analyses were exploratory and not supported by formal interaction tests. In children aged 0 to 5 years, those delivered by planned CS had an adjusted HR of 1.37 (95% CI, 1.05–1.78) for ALL and 1.35 (95% CI, 1.02–1.80) for B-cell precursor ALL. Among boys, the adjusted HR for B-cell precursor ALL after planned CS was 1.41 (95% CI, 1.00–1.99), while no significant increase in risk was observed in girls.
The association was also more pronounced among children diagnosed before age six with common subtypes of B-cell precursor ALL, including those with ETV6::RUNX1 rearrangements and high hyperdiploidy. Among children diagnosed before age 6 with these subtypes, the adjusted HR following planned CS was 1.57 (95% CI, 1.00–2.33).
Unplanned CS was not associated with increased risk. For example, children delivered by unplanned pre-labor CS had an adjusted HR of 0.89 (95% CI, 0.61–1.29) for ALL and 0.71 (95% CI, 0.44–1.14) for B-cell precursor ALL, compared with vaginal delivery.
In total, 375,841 children in the cohort were delivered by CS, including 136,342 by planned CS. Children born by CS were more likely to be small or large for gestational age and had higher rates of birth defects. Their mothers were more often older and more likely to have diabetes (3.6% vs 1.3%), preeclampsia (7.3% vs 2.2%), or elevated body mass index (34.4% vs 28.9%).
According to lead author Christina-Evmorfia Kampitsi of the Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, and colleagues, “Adjusted and unadjusted estimates were largely similar, supporting the notion that confounding by indication does not explain the increased ALL risk associated with planned CS.”
Children were followed from birth until cancer diagnosis, death, emigration, their 20th birthday, or the end of follow-up in December 2015.
Researchers concluded that planned CS was associated with an increased risk of B-cell precursor ALL, particularly in boys and in early childhood. The association was not explained by maternal or perinatal health factors.
The authors reported no conflicts of interest.
Source: International Journal of Cancer