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A meta-analysis of the association between day-care attendance and childhood acute lymphoblastic leukaemia
Kevin Y Urayama1, Patricia A Buffler, Emily R Gallagher
1School of Public Health, University of California, Berkeley, CA 94720, USA. urayamak@fellows.iarc.fr
Insights
Attending daycare in early childhood is linked to a lower risk of childhood acute lymphoblastic leukaemia (ALL). This suggests early exposure to common infections may be protective against ALL.
Area of Science:
- Pediatric Oncology
- Epidemiology
- Infectious Disease
Background:
- Childhood acute lymphoblastic leukaemia (ALL) may arise from unusual responses to common infections.
- Early-life exposure to infections is hypothesized to be protective against ALL.
- Daycare attendance facilitates exposure to common childhood infections.
Purpose of the Study:
- To meta-analyze the association between daycare attendance and childhood ALL risk.
- To investigate if early-life infection exposure is protective against ALL.
Main Methods:
- A meta-analysis of 14 case-control studies was conducted.
- Searches included PubMed and bibliographies of relevant publications.
- Studies were observational, of any size/location, and in English.
Main Results:
- Daycare attendance was associated with a reduced risk of ALL (OR = 0.76).
- Reduced risk was observed for early-life daycare (<2 years) (OR = 0.79) and unspecified timing (OR = 0.81).
- Findings were consistent in subgroup and sensitivity analyses.
Conclusions:
- Strong evidence supports an association between early childhood infection exposure and reduced ALL risk.
- A 'hygiene hypothesis' may explain the observed association.
- Prophylactic interventions in infancy could be a future possibility.
Background:
Childhood acute lymphoblastic leukaemia (ALL) may be the result of a rare response to common infection(s) acquired by personal contact with infected individuals. A meta-analysis was conducted to examine the relationship between day-care attendance and risk of childhood ALL, specifically to address whether early-life exposure to infection is protective against ALL.
Methods:
Searches of the PubMed database and bibliographies of publications on childhood leukaemia and infections were conducted. Observational studies of any size or location and published in English resulted in the inclusion of 14 case-control studies.
Results:
The combined odds ratio (OR) based on the random effects model indicated that day-care attendance is associated with a reduced risk of ALL [OR = 0.76, 95% confidence interval (CI): 0.67, 0.87]. In subgroup analyses evaluating the influence of timing of exposure, a similarly reduced effect was observed for both day-care attendance occurring early in life (< or =2 years of age) (OR = 0.79, 95% CI: 0.65, 0.95) and day-care attendance with unspecified timing (anytime prior to diagnosis) (OR = 0.81, 95% CI: 0.70, 0.94). Similar findings were observed with seven studies in which common ALL were analysed separately. The reduced risk estimates persisted in sensitivity analyses that examined the sources of study heterogeneity.
Conclusions:
This analysis provides strong support for an association between exposure to common infections in early childhood and a reduced risk of ALL. Implications of a 'hygiene'-related aetiology suggest that some form of prophylactic intervention in infancy may be possible.
