A meta-analysis of the association between day-care attendance and childhood acute lymphoblastic leukaemia

Abstract

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.

Figure 1

Forest plot displaying ORs and 95% CIs of studies examining the association between day-care attendance and risk of childhood ALL. The risk estimates are plotted with boxes and the area of each box is inversely proportional to the variance of the estimated effect. The horizontal lines represent the 95% CIs of the risk estimate for each study. The solid vertical line at 1.0 represents a risk estimate of no effect. The dashed vertical line represents the combined risk estimate (OR = 0.76), and the width of the diamond is the 95% CI for this risk estimate (0.67–0.87).

Figure 2

Plot showing results of sensitivity meta-analyses evaluating the influence of potential biases within individual studies on combined risk estimates. RDD, random digit dialing.