The Interplay of Cesarean-Section Delivery and First-Birth Order as Risk Factors in Acute Lymphoblastic Leukemia

Area of Science:

• Pediatric Oncology
• Immunology
• Microbiome Research

Background:

• Childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is linked to early-life exposures like cesarean section (C-section) and being the first child.
• These exposures are thought to influence infant microbiome acquisition, crucial for immune system priming.
• Dysregulated immune responses in infancy may increase susceptibility to BCP-ALL.

Purpose of the Study:

• To investigate the association between immune-stimulating risk factors and BCP-ALL development.
• To examine the impact of birth mode (C-section vs. vaginal) and birth order on BCP-ALL risk.
• To explore potential interactions between birth exposures and BCP-ALL risk.

Main Methods:

• A case-control study involving 1,126 children with ALL (78.5% BCP-ALL) and 2,252 age- and sex-matched controls from Brazil (2002-2020).
• Data collected from the EMiLI study group and the National Placental and Umbilical Cord Blood Bank.
• Multiple logistic regression models were used, adjusted for relevant covariates.

Main Results:

• C-section delivery showed an increased risk for ALL (OR: 1.10) and BCP-ALL (OR: 1.09).
• Being the firstborn child was also associated with increased ALL risk.
• Firstborn children delivered via C-section had a significantly higher risk for ALL (OR: 2.33) compared to non-first, vaginally born children.
• Firstborns delivered by C-section and not breastfed had a further increased risk for ALL (OR: 2.32) and BCP-ALL (OR: 2.37).

Conclusions:

• Findings support the hypothesis that early-life exposures influencing microbiome composition and adrenal pathways contribute to BCP-ALL risk.
• These results highlight the importance of infant microbiome acquisition for immune system development and ALL prevention.
• The study encourages further research into preventive interventions for BCP-ALL.