Maternal Early Life Factors Associated with Hormone Levels and the Risk of Having a Child with an Autism Spectrum Disorder in the Nurses Health Study II

  • Kristen Lyall
  • David L. Pauls
  • Susan Santangelo
  • Donna Spiegelman
  • Alberto Ascherio
Original Paper


It is not known whether reproductive factors early in the mother’s life influence risk of autism spectrum disorders (ASD). We assessed maternal age at menarche, menstrual cycle characteristics during adolescence, oral contraceptive use prior to first birth, body shape, and body mass index (BMI) in association with ASD using binomial regression in a cohort study of 61,596 women, including 743 cases. Overall, early life factors were not associated with ASD, though early age at menarche (RR for age 10 or less = 1.54, 95% CI 1.18, 2.02, p = 0.0002) and BMI at age 18 of ≥30 (RR 2.03, 95% CI 1.34, 3.08, p = 0.0008) were significantly associated with increased risk of ASD. Further work should investigate the potential influence of these factors.


Autism spectrum disorders Reproductive risk factors Hormonal factors 


  1. Baer, H., Colditz, G. A., Rosner, B., Michels, K. B., Rich-Edwards, J. W., Hunter, D. J., et al. (2005). Body fatness during childhood and adolescence and incidence of breast cancer in premenopausal women: A prospective cohort study. Breast Cancer Research, 7(3), R314–R325.PubMedCrossRefGoogle Scholar
  2. Baron-Cohen, S., Lutchmaya, S., & Knickmeyer, R. (2004). Prenatal testosterone in mind. Cambridge: MIT Press.Google Scholar
  3. Bolton, P. F., Murphy, M., MacDonald, H., Whitlock, B., Pickles, A., & Rutter, M. (1997). Obstetric complications in autism: Consequences or causes of the condition? Journal of the American Academy of Child and Adolescent Psychiatry, 36(2), 272–281.PubMedCrossRefGoogle Scholar
  4. Bos, E. H., Bouhuys, A. L., Geerts, E., Van Os, T. W., Van der Spoel, I. D., Brouwer, W. H., et al. (2005). Cognitive, physiological, and personality correlates of recurrence of depression. Journal of Affective Disorders, 87(2–3), 221–229.PubMedCrossRefGoogle Scholar
  5. Brimacombe, M., Ming, X., & Lamendola, M. (2007). Prenatal and birth complications in autism. Maternal and Child Health Journal, 11, 73–79.PubMedCrossRefGoogle Scholar
  6. Carlsen, S., Jacobsen, G., & Romundstad, P. (2006). Maternal testosterone levels during pregnancy are associated with offspring size at birth. European Journal of Endocrinology, 155(2), 365–370.PubMedCrossRefGoogle Scholar
  7. Carmichael, A. R., & Bates, T. (2004). Obesity and breast cancer: A review of the literature. Breast, 13, 85–92.PubMedCrossRefGoogle Scholar
  8. CDC. (2006). Mental health in the United States: parental report of diagnosed autism in children aged 4–17 years–United States, 2003–2004. Mmwr. Morbidity and Mortality Weekly Report, 55(17), 481–486.Google Scholar
  9. Chapman, D., & Nam, J. M. (1968). Asymptotic power of chi square tests for linear trends in proportions. Biometrics, 24, 315–327.PubMedCrossRefGoogle Scholar
  10. Colditz, G. A., Manson, J. E., & Hankinson, S. E. (1997). The Nurses’ Health Study: 20-year contribution to the understanding of health among women. Journal of Womens Health, 6(1), 49–62.CrossRefGoogle Scholar
  11. Colditz, G., Martin, P., Stampfer, M. J., Willett, W. C., Sampson, L., Rosner, B., et al. (1986). Validation of questionnaire information on risk factors and disease outcomes in a prospective cohort study of women. American Journal of Epidemiology, 123(5), 894–900.PubMedGoogle Scholar
  12. Durrleman, S., & Simon, R. (1989). Flexible regression models with cubic splines. Statistics in Medicine, 8, 551–561.PubMedCrossRefGoogle Scholar
  13. Faraone, S. V., Biederman, J., & Milberger, S. (1995). How reliable are maternal reports of their children’s psychopathology? One-year recall of psychiatric diagnoses of ADHD children. Journal of the American Academy of Child and Adolescent Psychiatry, 34(8), 1001–1008.PubMedCrossRefGoogle Scholar
  14. Feskanich, D., Cho, E., Schaumberg, D. A., Colditz, G. A., & Hankinson, S. E. (2008). Menopausal and reproductive factors and risk of age-related macular degeneration. Archives of Ophthalmology, 126(4), 519–524.PubMedCrossRefGoogle Scholar
  15. Fombonne, E. (2005). The changing epidemiology of autism. Journal of Applied Research in Intellectual Disabilities, 18, 281–294.CrossRefGoogle Scholar
  16. Gardener, H., Spiegelman, D., & Buka, S. (2009). Prenatal risk factors for autism: Comprehensive meta-analysis. The British Journal of Psychiatry, 195, 7–14.PubMedCrossRefGoogle Scholar
  17. Golub, M., Collman, G. W., Foster, P. M., Kimmel, C. A., Rajpert-De Meyts, E., Reiter, E. O., et al. (2008). Public health implications of altered puberty timing. Pediatrics, 121(Suppl 3), S218–S230.PubMedCrossRefGoogle Scholar
  18. Govindarajulu, U., Spiegelman, D., Thurston, S. W., Ganguli, B., & Eisen, E. A. (2007). Comparing smoothing techniques in Cox models for exposure-response relationships. Statistics in Medicine, 26(20), 3735–3752.PubMedCrossRefGoogle Scholar
  19. Harris, M., Prior, J. C., & Koehoorn, M. (2008). Age at menarche in the Canadian population: Secular trends and relationship to adulthood BMI. Journal of Adolescent Health, 43(6), 548–554.PubMedCrossRefGoogle Scholar
  20. Hines, M. (2006). Prenatal testosterone and gender-related behaviour. European Journal of Endocrinology, 155(Suppl 1), S115–S121.PubMedCrossRefGoogle Scholar
  21. Juul-Dam, N., Townsend, J., & Courchesne, E. (2001). Prenatal, perinatal, and neonatal factors in autism, pervasive developmental disorder-not otherwise specified, and the general population. Pediatrics, 107(4), E63.PubMedCrossRefGoogle Scholar
  22. Laitinen, J., Power, C., & Järvelin, M. R. (2001). Family social class, maternal body mass index, childhood body mass index, and age at menarche as predictors of adult obesity. American Journal of Clinical Nutrition, 74(3), 287–294.PubMedGoogle Scholar
  23. Larsson, H. J., Eaton, W. W., Madsen, K. M., Vestergaard, M., Olesen, A. V., Agerbo, E., et al. (2005). Risk factors for autism: perinatal factors, parental psychiatric history, and socioeconomic status. American Journal of Epidemiology, 161(10), 916–925. discussion 926-8.PubMedCrossRefGoogle Scholar
  24. Lauritsen, M. B., Pedersen, C. B., & Mortensen, P. B. (2005). Effects of familial risk factors and place of birth on the risk of autism: A nationwide register-based study. Journal of Child Psychology and Psychiatry, 46(9), 963–971.PubMedCrossRefGoogle Scholar
  25. London, E. A., & Etzel, R. A. (2000). The environment as an etiologic factor in autism: A new direction for research. Environmental Health Perspectives, 108 Suppl 3, 401–404.PubMedCrossRefGoogle Scholar
  26. Lyall, K., Pauls D. L., Santangelo S., Speigelman D., & Ascherio A. (2010). Association between ovulation inducing drug use, infertility, and autism spectrum disorders in the Nurses’ Health Study II. Manuscript submitted for publication.Google Scholar
  27. Lyall, K., Pauls D. L., Speigelman D., Ascherio A., & Santangelo, S. (2009). Pregnancy complications and obstetric suboptimality as risk factors for autism spectrum disorders in children of the Nurses’ Health Study II. Manuscript submitted for publication.Google Scholar
  28. Mather, A., Cox, B. J., Enns, M. W., & Sareen, J. (2009). Associations of obesity with psychiatric disorders and suicidal behaviors in a nationally representative sample. Journal of Psychosomatic Research, 66(4), 277–285.PubMedCrossRefGoogle Scholar
  29. Mucci, L. A., Lagiou, P., Hsieh, C. C., Tamimi, R., Hellerstein, S., Vatten, L., et al. (2004). A prospective study of pregravid oral contraceptive use in relation to fetal growth. BJOG: An International Journal of Obstetrics and Gynaecology, 111(9), 989–995.CrossRefGoogle Scholar
  30. Must, A., Willett, W. C., & Dietz, W. H. (1993). Remote recall of childhood height, weight, and body build by elderly subjects. American Journal of Epidemiology, 138, 56–64.PubMedGoogle Scholar
  31. Rothman, K. J. (1977). Fetal loss, twinning and birth weight after oral contraceptive use. New England Journal of Medicine, 297, 468–471.PubMedCrossRefGoogle Scholar
  32. Spiegelman, D., & Hertzmark, E. (2005). Easy SAS calculations for risk or prevalence ratios and differences. American Journal of Epidemiology, 162(3), 199–200.PubMedCrossRefGoogle Scholar
  33. Terry, K., Willett, W. C., Rich-Edwards, J. W., Hunter, D. J., & Michels, K. B. (2005). Menstrual cycle characteristics and incidence of premenopausal breast cancer. Cancer Epidemiology, Biomarkers and Prevention, 14(6), 1509–1513.PubMedCrossRefGoogle Scholar
  34. Tomeo, C. A., Rich-Edwards, J. W., Michels, K. B., Berkey, C. S., Hunter, D. J., Frazier, A. L., et al. (1999). Reproducibility and validity of maternal recall of pregnancy-related events. Epidemiology, 10(6), 774–777.PubMedCrossRefGoogle Scholar
  35. Torloni, M., Betrán, A. P., Horta, B. L., Nakamura, M. U., Atallah, A. N., Moron, A. F., et al. (2009). Prepregnancy BMI and the risk of gestational diabetes: A systematic review of the literature with meta-analysis. Obesity Reviews, 10(4), 487–488.CrossRefGoogle Scholar
  36. Torrey, E., Hersh, S. P., & McCabe, K. D. (1975). Early childhood psychosis and bleeding during pregnancy. A prospective study of gravid women and their offspring. Journal of Autism and Childhood Schizophrenia, 5(4), 287–297.PubMedCrossRefGoogle Scholar
  37. Troisi, R., Potischman, N., Roberts, J. M., Harger, G., Markovic, N., Cole, B., et al. (2003). Correlation of serum hormone concentrations in maternal and umbilical cord samples. Cancer Epidemiology, Biomarkers and Prevention, 12(5), 452–456.PubMedGoogle Scholar
  38. Troy, L. M., Hunter, D. J., Manson, J. E., Colditz, G. A., Stampfer, M. J., & Willett, W. C. (1995). The validity of recalled weight among younger women. International Journal of Obesity and Related Metabolic Disorders, 19(8), 570–572.PubMedGoogle Scholar
  39. Tworoger, S., Eliassen, A. H., Missmer, S. A., Baer, H., Rich-Edwards, J., Michels, K. B., et al. (2006). Birthweight and body size throughout life in relation to sex hormones and prolactin concentrations in premenopausal women. Cancer Epidemiology, Biomarkers and Prevention, 15(12), 2494–2501.PubMedCrossRefGoogle Scholar
  40. van de Beek, C., van Goozen, S. H., Buitelaar, J. K., & Cohen-Kettenis, P. T. (2009). Prenatal sex hormones (maternal and amniotic fluid) and gender-related play behavior in 13-month-old Infants. Archives of Sexual Behavior, 38(1), 6–15.PubMedCrossRefGoogle Scholar
  41. Vessey, M., Meisler, L., Flavel, R., & Yeates, D. (1979). Outcome of pregnancy in women using different methods of contraception. British Journal of Obstetrics and Gynaecology, 86, 548–556.PubMedCrossRefGoogle Scholar
  42. Wacholder, S. (1986). Binomial regression in GLIM: Estimating risk ratios and risk differences. American Journal of Epidemiology, 123(1), 174–182.PubMedGoogle Scholar
  43. Wilkerson, D., Volpe, A. G., Dean, R. S., & Titus, J. B. (2002). Perinatal complications as predictors of infantile autism. International Journal of Neuroscience, 112(9), 1085–1098.PubMedCrossRefGoogle Scholar
  44. Zhang, Y., Graubard, B. I., Longnecker, M. P., Stanczyk, F. Z., Klebanoff, M. A., & McGlynn, K. A. (2007). Maternal hormone levels and perinatal characteristics: Implications for testicular cancer. Annals of Epidemiology, 17(2), 85–92.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Kristen Lyall
    • 1
  • David L. Pauls
    • 1
    • 2
    • 3
  • Susan Santangelo
    • 1
    • 2
    • 3
  • Donna Spiegelman
    • 4
  • Alberto Ascherio
    • 5
    • 6
  1. 1.Department of EpidemiologyHarvard School of Public HealthBostonUSA
  2. 2.Department of PsychiatryHarvard Medical SchoolBostonUSA
  3. 3.The Neurodevelopmental Genetics Unit, Center for Human Genetic ResearchMassachusetts General HospitalBostonUSA
  4. 4.Departments of Epidemiology and BiostatisticsSan FranciscoUSA
  5. 5.Departments of Epidemiology and NutritionHarvard School of Public HealthBostonUSA
  6. 6.Channing Laboratory, Department of MedicineThe Brigham and Women’s Hospital and Harvard Medical SchoolBostonUSA

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