The Role of Prenatal, Obstetric and Neonatal Factors in the Development of Autism

  • Linda Dodds
  • Deshayne B. Fell
  • Sarah Shea
  • B. Anthony Armson
  • Alexander C. Allen
  • Susan Bryson
Original Paper


We conducted a linked database cohort study of infants born between 1990 and 2002 in Nova Scotia, Canada. Diagnoses of autism were identified from administrative databases with relevant diagnostic information to 2005. A factor representing genetic susceptibility was defined as having an affected sibling or a mother with a history of a psychiatric or neurologic condition. Among 129,733 children, there were 924 children with an autism diagnosis. The results suggest that among those with low genetic susceptibility, some maternal and obstetric factors may have an independent role in autism etiology whereas among genetically susceptible children, these factors appear to play a lesser role. The role of pre-pregnancy obesity and excessive weight gain during pregnancy on autism risk require further investigation.


Autism Cohort Prenatal Pregnancy Neonatal Epidemiology 



The authors thank the Reproductive Care Program of Nova Scotia and the Population Health Research Unit at Dalhousie University for facilitating access to the data and Anne Spencer for help with data analysis. This study was funded by a grant from the Cure Autism Now Foundation (now Autism Speaks). Although this research is based in part on data obtained from the Population Health Research Unit, the observations and opinions expressed are those of the authors and do not represent those of the Population Health Research Unit.


  1. Ashwood, P., Kwong, C., Hansen, R., Hertz-Picciotto, I., Croen, L., Krakowiak, P., et al. (2008). Brief report: Plasma leptin levels are elevated in autism: Association with early onset phenotype? Journal of Autism and Developmental Disorders, 38(1), 169–175. doi: 10.1007/s10803-006-0353-1.PubMedCrossRefGoogle Scholar
  2. Bienvenu, T., Philippe, C., De Roux, N., Raynaud, M., Bonnefond, J. P., Pasquier, L., et al. (2006). The incidence of Rett syndrome in France. Pediatric Neurology, 34(5), 372–375. doi: 10.1016/j.pediatrneurol.2005.10.013.PubMedCrossRefGoogle 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. Bryson, S. E., & Smith, I. M. (1998). Epidemiology of autism: Prevalence, associated characteristics, and implications for research and service delivery. MRDD Research Reviews, 4, 97–103.Google Scholar
  5. Bryson, S. E., Smith, I. M., & Eastwood, D. (1988). Obstetrical suboptimality in autistic children. Journal of the American Academy of Child and Adolescent Psychiatry, 27(4), 418–422.PubMedCrossRefGoogle Scholar
  6. Burd, L., Fisher, W., Kerbeshian, J., Vesely, B., Durgin, B., & Reep, P. (1988). A comparison of breastfeeding rates among children with pervasive developmental disorder, and controls. Journal of Developmental and Behavioral Pediatrics: JDBP, 9(5), 247–251.PubMedCrossRefGoogle Scholar
  7. Burd, L., Severud, R., Kerbeshian, J., & Klug, M. G. (1999). Prenatal and perinatal risk factors for autism. Journal of Perinatal Medicine, 27(6), 441–450.PubMedCrossRefGoogle Scholar
  8. Chappell, L. C., Seed, P. T., Briley, A., Kelly, F. J., Hunt, B. J., Charnock-Jones, D. S., et al. (2002). A longitudinal study of biochemical variables in women at risk of preeclampsia. American Journal of Obstetrics and Gynecology, 187(1), 127–136.PubMedCrossRefGoogle Scholar
  9. Considine, R. V., Sinha, M. K., Heiman, M. L., Kriauciunas, A., Stephens, T. W., Nyce, M. R., et al. (1996). Serum immunoreactive-leptin concentrations in normal-weight and obese humans. The New England Journal of Medicine, 334(5), 292–295.PubMedCrossRefGoogle Scholar
  10. Croen, L. A., Grether, J. K., & Selvin, S. (2002). Descriptive epidemiology of autism in a california population: Who is at risk? Journal of Autism and Developmental Disorders, 32(3), 217–224.PubMedCrossRefGoogle Scholar
  11. Curtin, C., Bandini, L. G., Perrin, E. C., Tybor, D. J., & Must, A. (2005). Prevalence of overweight in children and adolescents with attention deficit hyperactivity disorder and autism spectrum disorders: A chart review. BMC Pediatrics, 5, 48. doi: 10.1186/1471-2431-5-48.PubMedCrossRefGoogle Scholar
  12. Deykin, E. Y., & MacMahon, B. (1980). Pregnancy, delivery, and neonatal complications among autistic children. American Journal of Diseases of Children (1960), 134(9), 860–864.Google Scholar
  13. Dodds, L., Spencer, A., Shea, S., Fell, D., Armson, B. A., Allen, A. C., et al. (2009). Validity of autism diagnoses using administrative health data. Chronic Diseases in Canada, 29(3), 102–107.PubMedGoogle Scholar
  14. Fair, M., Cyr, M., Allen, A., Wen, S., Guyon, G., & Macdonald, R. (1999). Validation study for a record linkage of births and infant deaths in Canada (Catalogue No) (84F0013XIE ed.). Ottawa: Statistics Canada.Google Scholar
  15. Fair, M., Cyr, M., Allen, A. C., Wen, S. W., Guyon, G., & MacDonald, R. C. (2000). An assessment of the validity of a computer system for probabilistic record linkage of birth and infant death records in Canada the fetal and infant health study group. Chronic Diseases in Canada, 21(1), 8–13.PubMedGoogle Scholar
  16. Filipek, P. A., Accardo, P. J., Baranek, G. T., Cook, E. H., Jr, Dawson, G., Gordon, B., et al. (1999). The screening and diagnosis of autistic spectrum disorders. Journal of Autism and Developmental Disorders, 29(6), 439–484.PubMedCrossRefGoogle Scholar
  17. Fombone, E. (2002). Prevalence of childhood disintegrative disorder. Autism, 6(2), 149–157.PubMedCrossRefGoogle Scholar
  18. Fombonne, E. (2003). The prevalence of autism. JAMA: The Journal of the American Medical Association, 289(1), 87–89CrossRefGoogle Scholar
  19. Gillberg, C., & Gillberg, I. C. (1983). Infantile autism: A total population study of reduced optimality in the pre-, peri-, and neonatal period. Journal of Autism and Developmental Disorders, 13(2), 153–166.PubMedCrossRefGoogle Scholar
  20. Glasson, E. J., Bower, C., Petterson, B., de Klerk, N., Chaney, G., & Hallmayer, J. F. (2004). Perinatal factors and the development of autism: A population study. Archives of General Psychiatry, 61(6), 618–627. doi: 10.1001/archpsyc.61.6.618.PubMedCrossRefGoogle Scholar
  21. Hauguel-de Mouzon, S., Lepercq, J., & Catalano, P. (2006). The known and unknown of leptin in pregnancy. American Journal of Obstetrics and Gynecology, 194(6), 1537–1545. doi: 10.1016/j.ajog.2005.06.064.PubMedCrossRefGoogle Scholar
  22. Hultman, C. M., Sparen, P., & Cnattingius, S. (2002). Perinatal risk factors for infantile autism. Epidemiology (Cambridge, Mass), 13(4), 417–423.Google Scholar
  23. Jones, M. B., & Szatmari, P. (1988). Stoppage rules and genetic studies of autism. Journal of Autism and Developmental Disorders, 18(1), 31–40.PubMedCrossRefGoogle Scholar
  24. 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
  25. Larsson, H. J., Eaton, W. W., Madsen, K. M., Vestergaard, M., Olesen, A. V., Agerbo, E., Schendel, D., Thorsen, P., & Mortensen, P. B. (2005). Risk factors for autism: Perinatal factors, parental psychiatric history, and socioeconomic status. American Journal of Epidemiology, 161(10), 916–925; discussion 926–928. doi: 10.1093/aje/kwi123.Google Scholar
  26. Lauritsen, M., & Ewald, H. (2001). The genetics of autism. Acta Psychiatrica Scandinavica, 103(6), 411–427PubMedCrossRefGoogle Scholar
  27. Laurvick, C. L., de Klerk, N., Bower, C., Christodoulou, J., Ravine, D., Ellaway, C., et al. (2006). Rett syndrome in Australia: A review of the epidemiology. The Journal of Pediatrics, 148(3), 347–352. doi: 10.1016/j.jpeds.2005.10.037.PubMedCrossRefGoogle Scholar
  28. Leonard, H., Bower, C., & English, D. (1997). The prevalence and incidence of Rett Syndrome in Australia. European Child and Adolescent Psychiatry, 6(Suppl 1), 8–10.PubMedGoogle Scholar
  29. Leonard, H., de Klerk, N., Bourke, J., & Bower, C. (2005). Maternal health in pregnancy and intellectual disability in the offspring: A population-based study. Annals of Epidemiology. doi: 10.1016/j.annepidem.2005.05.002.
  30. Mouridsen, S. E. (2003). Childhood disintegrative disorder. Brain and Development, 25(4), 225–228PubMedCrossRefGoogle Scholar
  31. Piven, J., Simon, J., Chase, G. A., Wzorek, M., Landa, R., Gayle, J., et al. (1993). The etiology of autism: Pre-, peri- and neonatal factors. Journal of the American Academy of Child and Adolescent Psychiatry, 32(6), 1256–1263.PubMedCrossRefGoogle Scholar
  32. Reichenberg, A., Gross, R., Weiser, M., Bresnahan, M., Silverman, J., Harlap, S., et al. (2006). Advancing paternal age and autism. Archives of General Psychiatry, 63(9), 1026–1032. doi: 10.1001/archpsyc.63.9.1026.PubMedCrossRefGoogle Scholar
  33. Ritvo, E. R., Jorde, L. B., Mason-Brothers, A., Freeman, B. J., Pingree, C., Jones, M. B., et al. (1989). The UCLA-University of Utah epidemiologic survey of autism: Recurrence risk estimates and genetic counseling. The American Journal of Psychiatry, 146(8), 1032–1036.PubMedGoogle Scholar
  34. Robinson, H. E., O’Connell, C. M., Joseph, K. S., & McLeod, N. L. (2005). Maternal outcomes in pregnancies complicated by obesity. Obstetrics and Gynecology, 106(6), 1357–1364. doi: 10.1097/01.AOG.0000188387.88032.41.PubMedCrossRefGoogle Scholar
  35. Schultz, S. T., Klonoff-Cohen, H. S., Wingard, D. L., Akshoomoff, N. A., Macera, C. A., Ji, M., et al. (2006). Breastfeeding, infant formula supplementation, and autistic disorder: The results of a parent survey. International Breastfeeding Journal, 1, 16. doi: 10.1186/1746-4358-1-16.PubMedCrossRefGoogle Scholar
  36. Stein, D., Weizman, A., Ring, A., & Barak, Y. (2006). Obstetric complications in individuals diagnosed with autism and in healthy controls. Comprehensive Psychiatry, 47(1), 69–75. doi: 10.1016/j.comppsych.2005.01.001.PubMedCrossRefGoogle Scholar
  37. Sutera, S., et al. (2007). Predictors of optimal outcome in toddlers diagnosed with autism spectrum disorders. Journal of Autism and Developmental Disorders, 37(1), 98–107.PubMedCrossRefGoogle Scholar
  38. Tanoue, Y., & Oda, S. (1989). Weaning time of children with infantile autism. Journal of Autism and Developmental Disorders, 19(3), 425–434.PubMedCrossRefGoogle Scholar
  39. Turner, L. M., & Stone, W. L. (2007). Variability in outcome for children with an ASD diagnosis at age 2. Journal of Child Psychology and Psychiatry, 48, 793–802. doi: 10.1111/j.1469-7610.2007.01744.x.PubMedCrossRefGoogle Scholar
  40. Vanasse, A., Demers, M., Hemiari, A., & Courteau, J. (2006). Obesity in Canada: Where and how many? International Journal of Obesity (2005), 30(4), 677–683. doi: 10.1038/sj.ijo.0803168.
  41. Wetherby, A. M., Woods, J., Allen, L., Cleary, J., Dickinson, H., & Lord, C. (2004). Early indicators of autism spectrum disorders in the second year of life. Journal of Autism and Developmental Disorders, 34(5), 473–493.PubMedCrossRefGoogle Scholar
  42. Wier, M. L., Yoshida, C. K., Odouli, R., Grether, J. K., & Croen, L. A. (2006). Congenital anomalies associated with autism spectrum disorders. Developmental Medicine and Child Neurology, 48(6), 500–507. doi: 10.1017/S001216220600106X.PubMedCrossRefGoogle Scholar
  43. Williams, J. G., Higgins, J. P. T., & Brayne, C. E. G. (2006). Systematic review of prevalence studies of autism spectrum disorders. Archives of Disease in Childhood, 91, 8–15.PubMedCrossRefGoogle Scholar
  44. Yeargin-Allsopp, M., Rice, C., Karapurkar, T., Doernberg, N., Boyle, C., & Murphy, C. (2003). Prevalence of autism in a US metropolitan area. JAMA: The Journal of the American Medical Association, 289(1), 49–55CrossRefGoogle Scholar
  45. Zwaigenbaum, L., Szatmari, P., Jones, M. B., Bryson, S. E., MacLean, J. E., Mahoney, W. J., et al. (2002). Pregnancy and birth complications in autism and liability to the broader autism phenotype. Journal of the American Academy of Child and Adolescent Psychiatry, 41(5), 572–579.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Linda Dodds
    • 1
    • 2
    • 3
  • Deshayne B. Fell
    • 1
    • 4
  • Sarah Shea
    • 2
  • B. Anthony Armson
    • 3
  • Alexander C. Allen
    • 1
    • 2
    • 3
  • Susan Bryson
    • 2
  1. 1.Perinatal Epidemiology Research Unit, Departments of Obstetrics and Gynaecology and PediatricsDalhousie UniversityHalifaxCanada
  2. 2.Department of PediatricsDalhousie UniversityHalifaxCanada
  3. 3.Department of Obstetrics and GynaecologyDalhousie UniversityHalifaxCanada
  4. 4.University of Ottawa HospitalOttawaCanada

Personalised recommendations