Journal of Autism and Developmental Disorders

, Volume 40, Issue 12, pp 1423–1430 | Cite as

Maternal Infection Requiring Hospitalization During Pregnancy and Autism Spectrum Disorders

  • Hjördis Ó. AtladóttirEmail author
  • Poul Thorsen
  • Lars Østergaard
  • Diana E. Schendel
  • Sanne Lemcke
  • Morsi Abdallah
  • Erik T. Parner
Original Paper


Exposure to prenatal infection has been suggested to cause deficiencies in fetal neurodevelopment. In this study we included all children born in Denmark from 1980, through 2005. Diagnoses of autism spectrum disorders (ASDs) and maternal infection were obtained through nationwide registers. Data was analyzed using Cox proportional hazards regression. No association was found between any maternal infection and diagnosis of ASDs in the child when looking at the total period of pregnancy: adjusted hazard ratio = 1.14 (CI: 0.96–1.34). However, admission to hospital due to maternal viral infection in the first trimester and maternal bacterial infection in the second trimester were found to be associated with diagnosis of ASDs in the offspring, adjusted hazard ratio = 2.98 (CI: 1.29–7.15) and adjusted hazard ratio = 1.42 (CI: 1.08–1.87), respectively. Our results support prior hypotheses concerning early prenatal viral infection increasing the risk of ASDs.


Autism spectrum disorder Autism Infection Influenza Prenatal infection Maternal infection 



Funding was provided by the Aarhus University Research Foundation, the Aase and Ejnar Danielsens Foundation, the Augustinus Foundation, and the Familien Hede Nielsens Foundation. The funding sources did not participate in any part of the performance of the study. The authors thank the Aarhus University Hospital, Skejby for their assistance during the validation process.


The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.


  1. Andersen, T. F., Madsen, M., Jorgensen, J., Mellemkjoer, L., & Olsen, J. H. (1999). The Danish national hospital register. A valuable source of data for modern health sciences. Danish Medical Bulletin, 46, 263–268.PubMedGoogle Scholar
  2. Atladottir, H. O., Parner, E. T., Schendel, D., Dalsgaard, S., Thomsen, P. H., & Thorsen, P. (2007). Variation in incidence of neurodevelopmental disorders with season of birth. Epidemiology, 18, 240–245.CrossRefPubMedGoogle Scholar
  3. Autism Developmental Disabilities Monitoring Network. (2009). Prevalence of autism spectrum disorders. Morbidity and Mortality Weekly report (MMWR), 58, 1–20.Google Scholar
  4. Barak, Y., Ring, A., Sulkes, J., Gabbay, U., & Elizur, A. (1995). Season of birth and autistic disorder in Israel. American Journal of Psychiatry, 152, 798–800.PubMedGoogle Scholar
  5. Blaxill, M. F. (2004). What’s going on? The question of time trends in autism. Public Health Reports, 119, 536–551.CrossRefPubMedGoogle Scholar
  6. Brown, A. S., Begg, M. D., Gravenstein, S., Schaefer, C. A., Wyatt, R. J., Bresnahan, M., et al. (2004a). Serologic evidence of prenatal influenza in the etiology of schizophrenia. Archives of General Psychiatry, 61, 774–780.CrossRefPubMedGoogle Scholar
  7. Brown, A. S., Hooton, J., Schaefer, C. A., Zhang, H., Petkova, E., Babulas, V., et al. (2004b). Elevated maternal interleukin-8 levels and risk of schizophrenia in adult offspring. American Journal of Psychiatry, 161, 889–895.CrossRefPubMedGoogle Scholar
  8. Chess, S. (1977). Follow-up report on autism in congenital rubella. Journal of Autism and Childhood Schizophrenia, 7, 69–81.CrossRefPubMedGoogle Scholar
  9. Collier, S. A., Rasmussen, S. A., Feldkamp, M. L., & Honein, M. A. (2009). Prevalence of self-reported infection during pregnancy among control mothers in the national birth defects prevention study. Birth Defects Research. Part A, Clinical and Molecular Teratology, 85, 193–201.CrossRefPubMedGoogle Scholar
  10. Deykin, E. Y., & MacMahon, B. (1979). Viral exposure and autism. American Journal of Epidemiology, 109, 628–638.PubMedGoogle Scholar
  11. Djeu, J. Y., Matsushima, K., Oppenheim, J. J., Shiotsuki, K., & Blanchard, D. K. (1990). Functional activation of human neutrophils by recombinant monocyte-derived neutrophil chemotactic factor/IL-8. Journal of Immunology, 144, 2205–2210.Google Scholar
  12. Gillberg, C. (1990). Do children with autism have March birthdays? Acta Psychiatrica Scandinavica, 82, 152–156.CrossRefPubMedGoogle Scholar
  13. Knudsen, L. B., & Olsen, J. (1998). The Danish medical birth registry. Danish Medical Bulletin, 45, 320–323.PubMedGoogle Scholar
  14. Landau, E. C., Cicchetti, D. V., Klin, A., & Volkmar, F. R. (1999). Season of birth in autism: A fiction revisited. Journal of Autism and Developmental Disorders, 29, 385–393.CrossRefPubMedGoogle Scholar
  15. Lauritsen, M. B., Jorgensen, M., Madsen, K. M., Lemcke, S., Toft, S., Grove, J., et al. (2010). Validity of childhood autism in the Danish psychiatric central register: Findings from a cohort sample born 1990–1999. Journal of Autism and Developmental Disorders, 40, 139–148.CrossRefPubMedGoogle Scholar
  16. Libbey, J. E., Sweeten, T. L., McMahon, W. M., & Fujinami, R. S. (2005). Autistic disorder and viral infections. Journal of Neurovirology, 11, 1–10.CrossRefPubMedGoogle Scholar
  17. Mosbech, J., Jorgensen, J., Madsen, M., Rostgaard, K., Thornberg, K., & Poulsen, T. D. (1995). The national patient registry. Evaluation of data quality. Ugeskrift for Laeger, 157, 3741–3745.PubMedGoogle Scholar
  18. Munk-Jorgensen, P., & Mortensen, P. B. (1997). The Danish psychiatric central register. Danish Medical Bulletin, 44, 82–84.PubMedGoogle Scholar
  19. Nahmias, A. J., Nahmias, S. B., & Danielsson, D. (2006). The possible role of transplacentally-acquired antibodies to infectious agents, with molecular mimicry to nervous system sialic acid epitopes, as causes of neuromental disorders: Prevention and vaccine implications. Clinical & Developmental Immunology, 13, 167–183.CrossRefGoogle Scholar
  20. Parner, E. T., Schendel, D. E., & Thorsen, P. (2008). Autism prevalence trends over time in Denmark: Changes in prevalence and age at diagnosis. Archives of Pediatrics and Adolescent Medicine, 162, 1150–1156.CrossRefPubMedGoogle Scholar
  21. Patterson, P. H. (2009). Immune involvement in schizophrenia and autism: Etiology, pathology and animal models. Behavioural Brain Research, 204(2), 313–321.CrossRefPubMedGoogle Scholar
  22. Pedersen, C. B., Gotzsche, H., Moller, J. O., & Mortensen, P. B. (2006). The Danish civil registration system. A cohort of eight million persons. Danish Medical Bulletin, 53, 441–449.PubMedGoogle Scholar
  23. Ponzio, N. M., Servatius, R., Beck, K., Marzouk, A., & Kreider, T. (2007). Cytokine levels during pregnancy influence immunological profiles and neurobehavioral patterns of the offspring. Annals of the New York Academy of Sciences, 1107, 118–128.CrossRefPubMedGoogle Scholar
  24. Shi, L., Fatemi, S. H., Sidwell, R. W., & Patterson, P. H. (2003). Maternal influenza infection causes marked behavioral and pharmacological changes in the offspring. Journal of Neuroscience, 23, 297–302.PubMedGoogle Scholar
  25. Smith, S. E., Li, J., Garbett, K., Mirnics, K., & Patterson, P. H. (2007). Maternal immune activation alters fetal brain development through interleukin-6. Journal of Neuroscience, 27, 10695–10702.CrossRefPubMedGoogle Scholar
  26. Sorensen, H. J., Mortensen, E. L., Reinisch, J. M., & Mednick, S. A. (2009). Association between prenatal exposure to bacterial infection and risk of schizophrenia. Schizophrenia Bulletin, 35(3), 631–637.CrossRefPubMedGoogle Scholar
  27. Sweeten, T. L., Posey, D. J., & McDougle, C. J. (2004). Brief report: autistic disorder in three children with cytomegalovirus infection. Journal of Autism and Developmental Disorders, 34, 583–586.CrossRefPubMedGoogle Scholar
  28. World Health Organization. (1965). International classification of diseases, Revision 8.Google Scholar
  29. World Health Organization. (1993). International classification of diseases, 10th revision.Google Scholar
  30. Yamashita, Y., Fujimoto, C., Nakajima, E., Isagai, T., & Matsuishi, T. (2003). Possible association between congenital cytomegalovirus infection and autistic disorder. Journal of Autism and Developmental Disorders, 33, 455–459.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Hjördis Ó. Atladóttir
    • 1
    Email author
  • Poul Thorsen
    • 2
  • Lars Østergaard
    • 3
  • Diana E. Schendel
    • 4
  • Sanne Lemcke
    • 1
  • Morsi Abdallah
    • 1
  • Erik T. Parner
    • 5
  1. 1.Department of Epidemiology, Institute of Public HealthUniversity of AarhusÅrhus CDenmark
  2. 2.AtlantaUSA
  3. 3.Department of Infectious Diseases, Research Unit QAarhus University HospitalSkejbyDenmark
  4. 4.National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and PreventionAtlantaUSA
  5. 5.Department of Biostatistics, Institute of Public HealthUniversity of AarhusÅrhusDenmark

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