Risk of Childhood Leukemia

Objective. To conduct a systematic review to evaluate the evidence for the effect of breastfeeding on the risk of developing childhood leukemia. Review Methods. We sought studies providing data regarding the association of breastfeeding and occurrence of childhood leukemia. Studies were identified by using Medline, HHS Blueprint for Action on Breastfeeding, US Department of Health and Human Services Office on Women’s Health, Cochrane Database of Systematic Reviews, National Centre for Reviews and Dissemination, reference lists, and national experts. Methodologic quality was evaluated for each study by using criteria from the US Preventive Services Task Force and the National Health Service Centre for Reviews and Dissemination. Results. We reviewed 111 citations to identify 32 potentially eligible full-text articles. Of the 10 studies reviewed, only 4 were sufficient to provide at least fairquality evidence regarding the association between maternal breastfeeding and childhood leukemia. Studies conflicted regarding the protective effect of breastfeeding on childhood leukemia. In the 2 largest and highest quality studies, breastfeeding was associated with a significant risk reduction in one study with longer breastfeeding duration, reflecting greater protection, and a nonsignificant but suggestive difference in the other. Taken together, half of the studies associated breastfeeding with a lower risk of acute lymphocytic leukemia. Conclusions. There are few high-quality studies that examine the potential for a protective effect of breastfeeding for childhood leukemia. Furthermore, the few studies that exist disagree regarding the association. It is estimated that the United States spends $1.4 billion annually on the treatment of childhood leukemia. Patients, clinicians, and policy makers do not have the data that they need to make decisions regarding this important potential preventive measure. Pediatrics 2005; 116:e724–e731. URL: www.pediatrics.org/cgi/doi/10.1542/ peds.2005-0636; breastfeeding, human milk, leukemia, case-control studies, childhood malignancy, evidence review, review, evidence-based medicine, risk assessment, human, infant, female, pregnancy. ABBREVIATIONS. ALL, acute lymphocytic leukemia; SES, socioeconomic status; OR, odds ratio; CI, confidence interval; UKCCS, United Kingdom Childhood Cancer Study; AML, acute myelogenous leukemia. Leukemia is the most common malignancy in childhood, with an average annual incidence of 3.8 to 4.8 cases per 100 000 children aged 0 to 14 years.1 Leukemia accounts for 30% of all childhood malignancies, with 75% being diagnosed as acute lymphocytic leukemia (ALL). The incidence is slightly higher among males than females and 50% higher among white children than among black children.2 Although the etiology of childhood leukemia has been studied for a half of a century, causal factors associated with leukemia are largely unidentified. Certain conditions such as Down syndrome, other genetic abnormalities, and ionizing radiation exposures are thought to explain a small percentage of cases of leukemia.1,3 The infectious etiology of leukemia continues to be explored, with potential for bacterial and viral sources. After viruses were identified as the cause of some leukemias in animals,4 1 popular etiological hypothesis for human leukemia, especially that occurring in childhood, has been the result of a viral infection. Two additional observations suggest that immunologic factors may play a role in the development of childhood leukemia. The first factor originates from epidemiologic observations of geographic clusters of leukemia cases, suggesting that a common exposure (such as infectious exposure) may play a role.5 The second factor arises from observations that children with leukemia are less commonly found to be exposed very early in infancy to common infections compared with children without leukemia, promoting an aberrant response to future exposures.6 Because breastfeeding is noted for providing the newborn with passive immunity, protecting from some early infections, investigators have hypothesized that breastfeeding could reduce the risk of childhood leukemia.7 This review was conducted for the US Department of Health and Human Services Office on Women’s Health to evaluate the evidence for the effect of breastfeeding on the risk of developing childhood leukemia.