European Journal of Epidemiology

, Volume 30, Issue 12, pp 1229–1261 | Cite as

Risk for childhood leukemia associated with maternal and paternal age

  • Theodoros N. Sergentanis
  • Thomas P. Thomopoulos
  • Spyros P. Gialamas
  • Maria A. Karalexi
  • Stylianos-Iason Biniaris-Georgallis
  • Evangelia Kontogeorgi
  • Paraskevi Papathoma
  • Gerasimos Tsilimidos
  • Alkistis Skalkidou
  • Anastasia N. Iliadou
  • Eleni T. Petridou


The role of reproductive factors, such as parental age, in the pathogenesis of childhood leukemias is being intensively examined; the results of individual studies are controversial. This meta-analysis aims to quantitatively synthesize the published data on the association between parental age and risk of two major distinct childhood leukemia types in the offspring. Eligible studies were identified and pooled relative risk (RR) estimates were calculated using random-effects models, separately for childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Subgroup analyses were performed by study design, geographical region, adjustment factors; sensitivity analyses and meta-regression analyses were also undertaken. 77 studies (69 case–control and eight cohort) were deemed eligible. Older maternal and paternal age were associated with increased risk for childhood ALL (pooled RR = 1.05, 95 % CI 1.01–1.10; pooled RR = 1.04, 95 % CI 1.00–1.08, per 5 year increments, respectively). The association between maternal age and risk of childhood AML showed a U-shaped pattern, with symmetrically associated increased risk in the oldest (pooled RR = 1.23, 95 % CI 1.06–1.43) and the youngest (pooled RR = 1.23, 95 % CI 1.07–1.40) extremes. Lastly, only younger fathers were at increased risk of having a child with AML (pooled RR = 1.28, 95 % CI 1.04–1.59). In conclusion, maternal and paternal age represents a meaningful risk factor for childhood leukemia, albeit of different effect size by leukemia subtype. Genetic and socio-economic factors may underlie the observed associations. Well-adjusted studies, scheduled by large consortia, are anticipated to satisfactorily address methodological issues, whereas the potential underlying genetic mechanisms should be elucidated by basic research studies.


Childhood leukemia Parental age Meta-analysis Meta-regression Risk factor 



The authors would like to thank Dr. Jie Song, Karolinska Institutet, for the translation of Chinese articles on the field, as well as the corresponding authors of studies who replied to our Letters, as detailed in the Supplemental Results section.

Supplementary material

10654_2015_89_MOESM1_ESM.docx (648 kb)
Supplementary material 1 (DOCX 647 kb)
10654_2015_89_MOESM2_ESM.docx (309 kb)
Supplementary material 2 (DOCX 308 kb)
10654_2015_89_MOESM3_ESM.docx (56 kb)
Supplementary material 3 (DOCX 56 kb)


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Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  • Theodoros N. Sergentanis
    • 1
    • 2
  • Thomas P. Thomopoulos
    • 1
  • Spyros P. Gialamas
    • 1
  • Maria A. Karalexi
    • 1
  • Stylianos-Iason Biniaris-Georgallis
    • 1
  • Evangelia Kontogeorgi
    • 1
  • Paraskevi Papathoma
    • 1
  • Gerasimos Tsilimidos
    • 1
  • Alkistis Skalkidou
    • 3
  • Anastasia N. Iliadou
    • 2
  • Eleni T. Petridou
    • 1
  1. 1.Department of Hygiene, Epidemiology and Medical Statistics, Medical SchoolNational University of AthensAthensGreece
  2. 2.Department of Medical Epidemiology and BiostatisticsKarolinska InstitutetStockholmSweden
  3. 3.Department of Women’s and Children’s HealthUppsala UniversityUppsalaSweden

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