Cancer Causes & Control

, Volume 13, Issue 1, pp 15–25 | Cite as

Birth characteristics, maternal reproductive history, hormone use during pregnancy, and risk of childhood acute lymphocytic leukemia by immunophenotype (United States)

  • Xiao Ou Shu
  • Dehui Han
  • Richard K. Severson
  • Zhi Chen
  • Joseph P. Neglia
  • Gregory H. Reaman
  • Jonathan D. Buckley
  • Leslie L. Robison


Objective: To investigate the associations of birth characteristics and maternal reproductive factors with risk of childhood acute lymphoblastic leukemia (ALL) by immunophenotypic subtypes. Methods: Data collected from a case–control study including 1842 ALL cases (age < 15 years) and 1986 individually matched controls were analyzed. Exposure information was obtained through telephone interviews of parents. Results: Factors associated with risk of ALL from all subgroups combined included high birth weight (OR = 1.4, 95% CI = 1.1–1.8), high birth order (OR = 2.0, 95% CI = 1.3–3.0 for fourth-born child compared to first-born child), young maternal age (<20 compared to 25–29, OR = 1.4, 95% CI = 1.1–1.9), advanced paternal age ( > 39 compared to 25–29, OR = 1.4, 95% CI = 1.0–1.9), induced abortion prior to the index pregnancy (OR = 1.2, 95% CI = 1.0–1.4), and oral contraceptive use during the index pregnancy (OR = 1.5, 95% CI = 1.0–2.2) with children under the age of 2 (OR = 5.1, 95% CI = 1.0–24.7) being the predominantly affected group. Risk of early pre-B-cell ALL increased with advanced paternal age (OR = 1.7, 95% CI = 1.1–2.7) and high birth order (OR = 2.0, 95% CI = 1.1–3.6), while risk of pre-B-cell ALL increased with both younger (OR = 3.4, 95% CI = 1.4–8.4) and advanced maternal age (OR = 2.6, 95% CI = 1.1–5.9). T-cell ALL was associated with high birth weight (OR = 2.4, 95% CI = 1.1–5.5) and history of induced abortion (OR = 2.4, 95% CI = 1.3–4.5). Conclusion: This study suggests that the association of ALL with birth characteristics and maternal reproductive factors varies with the immunophenotype of the ALL. Future studies are needed to better understand the effect of maternal hormone in the development of subtype of childhood ALL.

ALL birth characteristics oral contraceptive 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Buckley JD, Buckley CM, Ruccione K, et al. (1994) Epidemiological characteristics of childhood acute lymphocytic leukemia. Analysis by immunophenotype. Leukemia 8: 856-864.Google Scholar
  2. 2.
    Westergaard T, Anderson 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: 939-947.Google Scholar
  3. 3.
    Van Steensel-Moll HA, Valkenburg HA, Vandenbroucke JP, van Zanen GE (1985) Are maternal fertility problems related to childhood leukaemia? Int J Epidemiology 14: 555-559.Google Scholar
  4. 4.
    Robison LL, Codd M, Gunderson P, Neglia JP, Smithson WA, King FL (1987) Birth weight as a risk factor for childhood acute lymphoblastic leukemia. Pediatr Hematol Oncol 4: 63-72.Google Scholar
  5. 5.
    Shu XO, Gao YT, Brinton LA, et al. (1988) A population-based case-control study of childhood leukemia in Shanghai. Cancer 62: 635-644.Google Scholar
  6. 6.
    Fasal E, Jackson EW, Klauber MR (1971) Birth characteristics and leukemia in childhood. J Natl Cancer Inst 47: 501-509.Google Scholar
  7. 7.
    Kaye SA, Robison LL, Smithson WA, Gunderson P, King FL, Neglia JP (1991) Maternal reproductive history and birth characteristics in childhood acute lymphoblastic leukemia. Cancer 68: 1351-1355.Google Scholar
  8. 8.
    Yeazel MW, Buckley JD, Woods WG, Ruccione K, Robison LL (1995) History of maternal fetal loss and increased risk of childhood acute leukemia at an early age. A report from the Children's Cancer Group. Cancer 75: 1718-1727.Google Scholar
  9. 9.
    Daling JR, Starzyk P, Olshan AF, Weiss NS (1984) Birth weight and the incidence of childhood cancer. J Natl Cancer Inst 72: 1039-1041.Google Scholar
  10. 10.
    Yeazel MW, Ross JA, Buckley JD, Woods WG, Ruccione K, Robison LL (1997) High birth weight and risk of specific childhood cancers: a report from the Children's Cancer Group. J Pediatr 131: 671-677.Google Scholar
  11. 11.
    Ross JA, Potter JD, Shu XO, Reaman GH, Lampkin B, Robison LL (1997) Evaluating the relationships among reproductive history, birth characteristics, and infant leukemia: a report from the Children's Cancer Group. Ann Epidemiol 7: 172-179.Google Scholar
  12. 12.
    Petridou E, Trichopoulos D, Kalapothaki V, et al. (1997) The risk profile of childhood leukaemia in Greece: a nationwide case-control study. Br J Cancer 76: 1241-1247.Google Scholar
  13. 13.
    Eisenberg DE, Sorahan T (1987) Birth weight and childhood cancer deaths. J Natl Cancer Inst 78: 1095-1100.Google Scholar
  14. 14.
    Forsberg JG, Ka¨ lle´ n B (1990) Pregnancy and delivery characteristics of women whose infants develop child cancer. A study based on registry information. APMIS 98: 37-42.Google Scholar
  15. 15.
    Roman E, Ansell P, Bull D (1997) Leukaemia and non-Hodgkin's lymphoma in children and young adults: are prenatal and neonatal factors important determinants of disease? Br J Cancer 76: 406-415.Google Scholar
  16. 16.
    Shaw G, Lavey R, Jackson R, Austin D (1984) Association of childhood leukemia with maternal age, birth order, and paternal occupation. A case-control study. Am J Epidemiol 119: 788-795.Google Scholar
  17. 17.
    Cnattingius S, Zack MM, Ekbom A, et al. (1995) Prenatal and neonatal risk factors for childhood lymphatic leukemia. J Natl Cancer Inst 87: 908-914.Google Scholar
  18. 18.
    Greaves MF (1990) Etiology of childhood acute lymphoblastic leukemia: A soluble problem? In: Gale RP, Hoelzer D, eds. Acute Lymphoblastic Leukemia: Proceedings of a Wyeth-Ayerst-UCLA Western Workshop in ALL. Held at Tapatio Springs, Texas, 29 November-2 December 1988. New York: Alan R. Liss, pp. 1-14.Google Scholar
  19. 19.
    Pui C-H, Behm FG, Crist WM (1993) Clinical and biologic relevance of immunologic marker studies in childhood acute lymphoblastic leukemia. Blood 82: 343-362.Google Scholar
  20. 20.
    Robison LL, Buckley JD, Bunin G (1995) Assessment of environmental and genetic factors in the etiology of childhood cancers: the Children's Cancer Group epidemiology program. Environ Health Perspect 103: 111-116.Google Scholar
  21. 21.
    Ross JA, Severson RK, Pollock BH, Robison LL (1996) Childhood cancer in the United States: a geographical analysis of cases from the Pediatric Cooperative Clinical Trials groups. Cancer 77: 201-207.Google Scholar
  22. 22.
    Robison LL, Daigle AE (1984) Control selection using random digit dialing for cases of childhood cancer. Am J Epidemiol 120: 164-166.Google Scholar
  23. 23.
    Breslow NE, Day NE (1980) The Analysis of Case-Control Studies. Statistical Methods in Cancer Research, vol. I. Lyon: International Agency for Research on Cancer. IARC Scientific Publications No. 32.Google Scholar
  24. 24.
    Adams MM, Erickson JD, Layde PM, Oakley GP (1981) Down's syndrome: recent trend in the United States. JAMA 246: 758-760.Google Scholar
  25. 25.
    Swan SH (2000) Intrauterine exposure to diethylstilbestrol: longterm effects in humans. APMIS 108: 793-804.Google Scholar
  26. 26.
    Depue RH, Pike MC, Henderson BE (1983) Estrogen exposure during gestation and risk of testicular cancer. J Natl Cancer Inst 71: 1151-1155.Google Scholar
  27. 27.
    Henderson BE, Benton B, Jing J, Yu MC, Pike MC (1979) Risk factors for cancer of the testis in young men. Int J Cancer 23: 598-602.Google Scholar
  28. 28.
    Ross JA, Perentesis JP, Robison LL, Davies SM (1996) Big babies and infant leukemia: a role for insulin-like growth factor-1? Cancer Causes Control 7: 553-559.Google Scholar
  29. 29.
    Petridou E, Panagiotopoulou K, Katsouyanni K, Spanos E, Trichopoulos D (1990) Tobacco smoking, pregnancy estrogens, and birth weight. Epidemiology 1: 247-250.Google Scholar
  30. 30.
    Olson JE, Shu XO, Ross JA, Pendergrass T, Robison LL (1997) Medical record validation of maternally reported birth characteristics and pregnancy-related events. A report from the Children's Cancer Group. Am J Epidemiol 145: 58-67.Google Scholar
  31. 31.
    Tilley BC, Barnes AB, Bergstralh E, et al. (1985) A comparison of pregnancy history recall and medical records. Implications for retrospective studies. Am J Epidemol 121: 269-281.Google Scholar

Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • Xiao Ou Shu
    • 1
    • 2
  • Dehui Han
    • 1
  • Richard K. Severson
    • 3
  • Zhi Chen
    • 1
  • Joseph P. Neglia
    • 1
  • Gregory H. Reaman
    • 4
  • Jonathan D. Buckley
    • 5
  • Leslie L. Robison
    • 1
  1. 1.Department of PediatricsUniversity of MinnesotaMinneapolisUSA
  2. 2.Children's Oncology GroupArcadiaUSA
  3. 3.Division of EpidemiologyKarmanos Cancer InstituteDetroitUSA
  4. 4.Department of Pediatric Hematology/OncologyChildren's National Medical CenterWashington DCUSA
  5. 5.Department of Preventive MedicineUniversity of Southern CaliforniaLos AngelesUSA

Personalised recommendations