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Childcare in the first 2 years of life reduces the risk of childhood acute lymphoblastic leukemia

Leukemia volume 22, pages 189–193 (2008)Cite this article

Based on the two-hit hypothesis, exposure to infections early in life has been hypothesized to reduce the risk of childhood acute lymphoblastic leukemia (ALL).1 The first hit should occur prenatally, whereas the second hit is related to delayed or diminished exposure to infections in early childhood, accompanied by an abnormal immune response.1, 2 So far, no specific infectious agents affecting the risk of childhood ALL have been identified. Instead, established risk factors for infections early in life, such as attendance to childcare, have been commonly used as a proxy measure of an early high infection load. Previous studies on childcare attendance have presented conflicting results, which could reflect childcare facility differences or that the effect of childcare on childhood ALL is modified by other factors. To evaluate the association between childcare attendance and childhood ALL, we conducted a nationwide study using Danish register data. The study was carried out as a matched case–control study nested in the cohort of all Danish children in the period 1989–2004. All incident cases of ALL diagnosed in children aged 0–15 years in Denmark were identified. Ten population controls per case were individually matched on date of birth and sex. Data were retrieved from three population-based registries: The Nordic Society of Paediatric Haematology and Oncology (NOPHO) database,3 the Danish Civil Registration System4 and the Childcare Database.5

During the study period, 559 children were diagnosed with childhood ALL in Denmark. The immune phenotype of 467 cases (84%) was B-cell precursor ALL, 73 cases (13%) had T-lineage ALL, 7 cases (1%) had mature B-cell ALL and for 12 cases (2%) information about immune phenotype was lacking in the register. The leukemic karyotype classified 199 cases (36%) as common ALL (t(12;21)(q13;q22) translocation or a hyperdiploid karyotype), whereas the karyotype was lacking or consisted of other aberrations for the remaining 360 cases. A white blood cell count of <50 was found in 430 cases (77%), whereas 118 cases (21%) had a white blood cell count of ⩾50. White blood cell count was not available for 11 cases. Median age at diagnosis was 4.0 years. Ten cases (2%) were diagnosed with childhood ALL before the age of 1.0 year. In Table 1, characteristics of cases and controls are shown. Information on childcare attendance during the first 2 years of life was complete for 176 cases (32%) and 1571 controls (28%). Overall, ever attendance to childcare was associated with a rate ratio (RR) of 0.68 (95% CI 0.48; 0.95). Children with incomplete registration of childcare but with one or more registration of childcare had a RR of 0.59 (0.43; 0.81). Each additional month enrolled in childcare was associated with an insignificantly decreasing RR of 0.98 (95% CI 0.94; 1.03). There was no statistically significant difference between different types of childcare (P=0.57). Increased risks of childhood ALL, however not significant, were seen with increasing birth weight and increasing maternal and paternal age. No significant main effect of birth order or population density on ALL risk was observed. Significantly fewer cases than controls were born outside of Denmark (4 vs 10%, P<0.01). None of the covariates listed in Table 1 changed the estimated effect of ever attendance to childcare on ALL risk by 5% or more; thus, crude estimates are presented. The variable changing the estimated effect of ever attendance to childcare the most was birth weight. When adjusted for birth weight, the estimate for ever attendance to childcare decreased to 0.65 (95% CI 0.47; 0.92).

Table 1 Cases, controls and RR of childhood ALL according to childcare characteristics and covariates
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Acknowledgements

This study was supported by the Danish Foundation of Child Cancer, the Health Insurance Foundation, the Egmont Foundation and Mikael Goldschmidt Holding A/S.

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Author notes

  1. K Schmiegelow: The author holds the Danish Childhood Cancer Foundation professorship in Pediatric Oncology.

Authors and Affiliations

  1. Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark

    M Kamper-Jørgensen, J Wohlfahrt, J Simonsen & H Hjalgrim

  2. School of Population Health, University of Auckland, Auckland, New Zealand

    A Woodward

  3. Bandim Health Project, Statens Serum Institut, Copenhagen, Denmark

    C S Benn

  4. Pediatric Clinic, The University Hospital Rigshospitalet and The Medical Faculty, University of Copenhagen, Copenhagen, Denmark

    K Schmiegelow

Authors
  1. M Kamper-Jørgensen
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  2. A Woodward
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  3. J Wohlfahrt
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  4. C S Benn
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  5. J Simonsen
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  6. H Hjalgrim
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Correspondence to M Kamper-Jørgensen.

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Kamper-Jørgensen, M., Woodward, A., Wohlfahrt, J. et al. Childcare in the first 2 years of life reduces the risk of childhood acute lymphoblastic leukemia. Leukemia 22, 189–193 (2008). https://doi.org/10.1038/sj.leu.2404884

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