Cancer Causes & Control

, Volume 25, Issue 7, pp 905–913 | Cite as

Maternal and birth characteristics and childhood rhabdomyosarcoma: a report from the Children’s Oncology Group

  • Philip J. LupoEmail author
  • Heather E. Danysh
  • Stephen X. Skapek
  • Douglas S. Hawkins
  • Logan G. Spector
  • Renke Zhou
  • M. Fatih Okcu
  • Karin Papworth
  • Erik B. Erhardt
  • Seymour Grufferman
Original paper



Previous assessments of childhood rhabdomyosarcoma have indicated maternal and birth characteristics may be associated with tumor development; however, much work remains to identify novel and confirm suspected risk factors. Our objective was to evaluate the associations between maternal and birth characteristics and childhood rhabdomyosarcoma.


This case–control study included 322 cases and 322 pair-matched controls. Cases were enrolled in a trial run by the Intergroup Rhabdomyosarcoma Study Group. Population-based controls were identified using random digit dialing and were individually matched to cases on race, sex, and age. Families of the case and control subjects participated in a telephone interview, which captured information on maternal characteristics (birth control use, number of prenatal visits, anemia, and abnormal bleeding during pregnancy) and birth characteristics [birth weight, preterm birth, and type of delivery (vaginal vs. cesarean)]. Conditional logistic regression models were used to calculate an odds ratio (OR) and 95 % confidence interval (CI) for each exposure, adjusted for age, race, sex, household income, and parental education. As the two most common histologic types of rhabdomyosarcoma are embryonal (n = 215) and alveolar (n = 66), we evaluated effect heterogeneity of these exposures.


The only characteristic that was associated with childhood rhabdomyosarcoma, and statistically significant, was abnormal vaginal bleeding during pregnancy (OR 1.75, 95 % CI 1.12–2.74). Birth control use (OR 1.45, 95 % CI 0.96–2.18), anemia during pregnancy (OR 1.27, 95 % CI 0.81–1.99), and preterm birth (OR 2.51, 95 % CI 0.74–8.49) were positively associated with childhood rhabdomyosarcoma, but were not statistically significant. Low birth weight [adjusted odds ratios (aOR) 4.46, 95 % CI 1.41–14.1] and high birth weight (aOR 2.41, 95 % CI 1.09–5.35) were strongly associated with alveolar rhabdomyosarcoma. However, these factors did not display significant effect heterogeneity between histologic types (p > 0.15 for all characteristics).


Overall, we found little evidence that these maternal and birth characteristics are strongly associated with childhood rhabdomyosarcoma.


Abnormal vaginal bleeding Epidemiology Rhabdomyosarcoma Soft tissue sarcoma 



This work was supported by US National Cancer Institute grants CA21244, CA24507, CA30318, CA30969, CA29139, and CA13539, and in part by Kurt Groten Family Research Scholars Award (P. Lupo).

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Ognjanovic S, Linabery AM, Charbonneau B, Ross JA (2009) Trends in childhood rhabdomyosarcoma incidence and survival in the United States, 1975–2005. Cancer 115:4218–4226PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Ries L, Smith M, Gurney J et al (1999) Cancer incidence and survival among children and adolescents: United States SEER Program 1975–1995. NIH Pub. No. 99-4649. National Cancer Institute, SEER Program, Bethesda, MDGoogle Scholar
  3. 3.
    Gurney JG, Young JL Jr., Roffers SD, Smith MA, Bunin GR (1999) Soft tissue sarcomas. Cancer Incidence and Survival Among Children and Adolescents: United States SEER Program 1975–1995. National Cancer Institute SEER ProgramGoogle Scholar
  4. 4.
    Malempati S, Hawkins DS (2012) Rhabdomyosarcoma: review of the Children’s Oncology Group (COG) Soft-Tissue Sarcoma Committee experience and rationale for current COG studies. Pediatr Blood Cancer 59:5–10PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Ruymann FB, Maddux HR, Ragab A et al (1988) Congenital anomalies associated with rhabdomyosarcoma: an autopsy study of 115 cases. A report from the Intergroup Rhabdomyosarcoma Study Committee (representing the Children’s Cancer Study Group, the Pediatric Oncology Group, the United Kingdom Children’s Cancer Study Group, and the Pediatric Intergroup Statistical Center). Med Pediatr Oncol 16:33–39PubMedCrossRefGoogle Scholar
  6. 6.
    Li FP, Fraumeni JF Jr (1969) Soft-tissue sarcomas, breast cancer, and other neoplasms. A familial syndrome? Ann Intern Med 71:747–752PubMedCrossRefGoogle Scholar
  7. 7.
    Yang P, Grufferman S, Khoury MJ et al (1995) Association of childhood rhabdomyosarcoma with neurofibromatosis type I and birth defects. Genet Epidemiol 12:467–474PubMedCrossRefGoogle Scholar
  8. 8.
    Diller L, Sexsmith E, Gottlieb A, Li FP, Malkin D (1995) Germline p53 mutations are frequently detected in young children with rhabdomyosarcoma. J Clin Invest 95:1606–1611PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Von Behren J, Spector LG, Mueller BA et al (2011) Birth order and risk of childhood cancer: a pooled analysis from five US States. Int J Cancer 128:2709–2716CrossRefGoogle Scholar
  10. 10.
    Grufferman S, Schwartz AG, Ruymann FB, Maurer HM (1993) Parents’ use of cocaine and marijuana and increased risk of rhabdomyosarcoma in their children. Cancer Causes Control 4:217–224PubMedGoogle Scholar
  11. 11.
    Grufferman S, Ruymann F, Ognjanovic S, Erhardt EB, Maurer HM (2009) Prenatal X-ray exposure and rhabdomyosarcoma in children: a report from the children’s oncology group. Cancer Epidemiol Biomarkers Prev 18:1271–1276PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Lupo PJ, Zhou R, Skapek SX, Hawkins DS, Spector LG, Scheurer ME, Fatih Okcu M, Melin B, Papworth K, Erhardt EB, Grufferman S (2013) Allergies, atopy, immune-related factors and childhood rhabdomyosarcoma: a report from the children’s oncology group. Int J Cancer 134(2):431–436Google Scholar
  13. 13.
    Johnson KJ, Carozza SE, Chow EJ et al (2009) Parental age and risk of childhood cancer: a pooled analysis. Epidemiology 20:475–483PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Ma X, Metayer C, Does MB, Buffler PA (2005) Maternal pregnancy loss, birth characteristics, and childhood leukemia (United States). Cancer Causes Control 16:1075–1083PubMedCrossRefGoogle Scholar
  15. 15.
    Oksuzyan S, Crespi CM, Cockburn M, Mezei G, Kheifets L (2013) Birth weight and other perinatal factors and childhood CNS tumors: a case-control study in California. Cancer Epidemiol 37:402–409PubMedCrossRefGoogle Scholar
  16. 16.
    Partap S, MacLean J, Von Behren J, Reynolds P, Fisher PG (2011) Birth anomalies and obstetric history as risks for childhood tumors of the central nervous system. Pediatrics 128:e652–e657PubMedCentralPubMedGoogle Scholar
  17. 17.
    Schmidt LS, Schuz J, Lahteenmaki P et al (2010) Fetal growth, preterm birth, neonatal stress and risk for CNS tumors in children: a Nordic population- and register-based case-control study. Cancer Epidemiol Biomarkers Prev 19:1042–1052PubMedCrossRefGoogle Scholar
  18. 18.
    Spector LG, Puumala SE, Carozza SE et al (2009) Cancer risk among children with very low birth weights. Pediatrics 124:96–104PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Westergaard T, Andersen PK, Pedersen JB et al (1997) Birth characteristics, sibling patterns, and acute leukemia risk in childhood: a population-based cohort study. J Natl Cancer Inst 89:939–947PubMedCrossRefGoogle Scholar
  20. 20.
    Ognjanovic S, Carozza SE, Chow EJ et al (2010) Birth characteristics and the risk of childhood rhabdomyosarcoma based on histological subtype. Br J Cancer 102:227–231PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Grufferman S, Wang HH, DeLong ER, Kimm SY, Delzell ES, Falletta JM (1982) Environmental factors in the etiology of rhabdomyosarcoma in childhood. J Natl Cancer Inst 68:107–113PubMedGoogle Scholar
  22. 22.
    Shrestha A, Ritz B, Ognjanovic S, Lombardi CA, Wilhelm M, Heck JE (2013) Early life factors and risk of childhood rhabdomyosarcoma. Front Public Health 1:17PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Ghali MH, Yoo KY, Flannery JT, Dubrow R (1992) Association between childhood rhabdomyosarcoma and maternal history of stillbirths. Int J Cancer 50:365–368PubMedCrossRefGoogle Scholar
  24. 24.
    Hartley AL, Birch JM, McKinney PA et al (1988) The Inter-Regional Epidemiological Study of Childhood Cancer (IRESCC): case control study of children with bone and soft tissue sarcomas. Br J Cancer 58:838–842PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Puumala SE, Carozza SE, Chow EJ et al (2009) Childhood cancer among twins and higher order multiples. Cancer Epidemiol Biomarkers Prev 18:162–168PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Sprehe MR, Barahmani N, Cao Y et al (2010) Comparison of birth weight corrected for gestational age and birth weight alone in prediction of development of childhood leukemia and central nervous system tumors. Pediatr Blood Cancer 54:242–249PubMedCentralPubMedGoogle Scholar
  27. 27.
    Grufferman S, Delzell E, Delong ER (1984) An approach to conducting epidemiologic research within cooperative clinical trials groups. J Clin Oncol 2:670–675PubMedGoogle Scholar
  28. 28.
    Bunin GR, Spector LG, Olshan AF et al (2007) Secular trends in response rates for controls selected by random digit dialing in childhood cancer studies: a report from the Children’s Oncology Group. Am J Epidemiol 166:109–116PubMedCrossRefGoogle Scholar
  29. 29.
    Glynn RJ, Rosner B (2004) Methods to evaluate risks for composite end points and their individual components. J Clin Epidemiol 57:113–122PubMedCrossRefGoogle Scholar
  30. 30.
    Strobino B, Pantel-Silverman J (1989) Gestational vaginal bleeding and pregnancy outcome. Am J Epidemiol 129:806–815PubMedGoogle Scholar
  31. 31.
    Ognjanovic S, Puumala S, Spector LG et al (2009) Maternal health conditions during pregnancy and acute leukemia in children with Down syndrome: a Children’s Oncology Group study. Pediatr Blood Cancer 52:602–608PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Williams CL, Bunch KJ, Stiller CA et al (2013) Cancer risk among children born after assisted conception. N Engl J Med 369:1819–1827PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Philip J. Lupo
    • 1
    Email author
  • Heather E. Danysh
    • 1
  • Stephen X. Skapek
    • 2
  • Douglas S. Hawkins
    • 3
  • Logan G. Spector
    • 4
  • Renke Zhou
    • 1
  • M. Fatih Okcu
    • 1
  • Karin Papworth
    • 5
  • Erik B. Erhardt
    • 6
  • Seymour Grufferman
    • 7
  1. 1.Department of Pediatrics, Texas Children’s Cancer CenterBaylor College of MedicineHoustonUSA
  2. 2.Children’s Medical CenterUniversity of Texas Southwestern Medical CenterDallasUSA
  3. 3.Seattle Children’s Hospital, University of Washington, and Fred Hutchinson Cancer Research CenterSeattleUSA
  4. 4.Division of Pediatric Epidemiology and Clinical Research, Department of PediatricsUniversity of MinnesotaMinneapolisUSA
  5. 5.Department of Radiation Sciences, OncologyUmeå UniversityUmeåSweden
  6. 6.Department of Mathematics and StatisticsUniversity of New MexicoAlbuquerqueUSA
  7. 7.Division of Epidemiology and Biostatistics, Department of Internal MedicineUniversity of New MexicoAlbuquerqueUSA

Personalised recommendations