Journal of Autism and Developmental Disorders

, Volume 45, Issue 12, pp 4015–4025 | Cite as

Maternal Infection During Pregnancy and Autism Spectrum Disorders

  • Ousseny Zerbo
  • Yinge Qian
  • Cathleen Yoshida
  • Judith K. Grether
  • Judy Van de Water
  • Lisa A. Croen
Original Paper

Abstract

We conducted a nested case–control study including 407 cases and 2,075 frequency matched controls to investigate the association between maternal infections during pregnancy and risk of autism spectrum disorders (ASD). Cases, controls, and maternal infections were ascertained from Kaiser Permanente Northern California clinical databases. No overall association between diagnoses of any maternal infection during pregnancy and ASD was observed [adjusted odds ratio (ORadj) = 1.15, 95 % confidence interval (CI) 0.92–1.43]. However, women with infections diagnosed during a hospital admission (ORadj = 1.48, 95 % CI 1.07–2.04), particularly bacterial infections (ORadj = 1.58, 95 % CI 1.06–2.37), were at increased risk of delivering a child with ASD. Multiple infections during pregnancy were associated with ASD (ORadj = 1.36, 95 % CI 1.05–1.78).

Keywords

Maternal infection Pregnancy Autism spectrum disorder 

References

  1. Abdallah, M. W., Larsen, N., Grove, J., Norgaard-Pedersen, B., Thorsen, P., Mortensen, E. L., et al. (2012). Amniotic fluid chemokines and autism spectrum disorders: An exploratory study utilizing a Danish Historic Birth Cohort. Brain, Behavior, and Immunity, 26(1), 170–176.CrossRefPubMedGoogle Scholar
  2. Abdallah, M. W., Larsen, N., Grove, J., Norgaard-Pedersen, B., Thorsen, P., Mortensen, E. L., et al. (2013). Amniotic fluid inflammatory cytokines: Potential markers of immunologic dysfunction in autism spectrum disorders. The World Journal of Biological Psychiatry, 14(7), 528–538. doi:10.3109/15622975.2011.639803.Google Scholar
  3. Abrahams, B. S., & Geschwind, D. H. (2008). Advances in autism genetics: On the threshold of a new neurobiology. Nature Reviews Genetics, 9(5), 341–355.PubMedCentralCrossRefPubMedGoogle Scholar
  4. Arndt, T. L., Stodgell, C. J., & Rodier, P. M. (2005). The teratology of autism. International Journal of Developmental Neuroscience, 23(2–3), 189–199.CrossRefPubMedGoogle Scholar
  5. Aronsson, F., Lannebo, C., Paucar, M., Brask, J., Kristensson, K., & Karlsson, H. (2002). Persistence of viral RNA in the brain of offspring to mice infected with influenza A/WSN/33 virus during pregnancy. Journal of Neurovirology, 8(4), 353–357.CrossRefPubMedGoogle Scholar
  6. Ashdown, H., Dumont, Y., Ng, M., Poole, S., Boksa, P., & Luheshi, G. N. (2006). The role of cytokines in mediating effects of prenatal infection on the fetus: Implications for schizophrenia. Molecular Psychiatry, 11(1), 47–55.CrossRefPubMedGoogle Scholar
  7. Atladottir, H. O., Henriksen, T. B., Schendel, D. E., & Parner, E. T. (2012). Autism after infection, febrile episodes, and antibiotic use during pregnancy: An exploratory study. Pediatrics, 130, e1447–e1454.PubMedCentralCrossRefPubMedGoogle Scholar
  8. Atladottir, H. O., Thorsen, P., Ostergaard, L., Schendel, D. E., Lemcke, S., Abdallah, M., et al. (2010). Maternal infection requiring hospitalization during pregnancy and autism spectrum disorders. Journal of Autism and Developmental Disorders, 40(12), 1423–1430.CrossRefPubMedGoogle Scholar
  9. Bauer, S., Kerr, B. J., & Patterson, P. H. (2007). The neuropoietic cytokine family in development, plasticity, disease and injury. Nature Reviews Neuroscience, 8(3), 221–232.CrossRefPubMedGoogle Scholar
  10. Braunschweig, D., & Van de Water, J. (2012). Maternal autoantibodies in autism. Archives of Neurology, 69(6), 693–699.CrossRefPubMedGoogle Scholar
  11. Cheng, Y., Chou, K. H., Chen, I. Y., Fan, Y. T., Decety, J., & Lin, C. P. (2010). Atypical development of white matter microstructure in adolescents with autism spectrum disorders. Neuroimage, 50(3), 873–882.CrossRefPubMedGoogle Scholar
  12. Chess, S. (1971). Autism in children with congenital rubella. Journal of Autism and Childhood Schizophrenia, 1(1), 33–47.CrossRefPubMedGoogle Scholar
  13. 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(3), 193–201.CrossRefGoogle Scholar
  14. Cram, L. F., Zapata, M. I., Toy, E. C., & Baker, B., I. I. I. (2002). Genitourinary infections and their association with preterm labor. American Family Physician, 65(2), 241–248.PubMedGoogle Scholar
  15. Croen, L. A., Grether, J. K., Hoogstrate, J., & Selvin, S. (2002). The changing prevalence of autism in California. Journal of Autism and Developmental Disorders, 32(3), 207–215.CrossRefPubMedGoogle Scholar
  16. Croen, L. A., Grether, J. K., Yoshida, C. K., Odouli, R., & Van de Water, J. (2005). Maternal autoimmune diseases, asthma and allergies, and childhood autism spectrum disorders: A case-control study. Archives of Pediatrics and Adolescent Medicine, 159(2), 151–157.CrossRefPubMedGoogle Scholar
  17. Croen, L. A., Matevia, M., Yoshida, C. K., & Grether, J. K. (2008). Maternal Rh D status, anti-D immune globulin exposure during pregnancy, and risk of autism spectrum disorders. American Journal of Obstetrics and Gynecology, 199(3), 234.e1–234.e6.Google Scholar
  18. Dalton, P., Deacon, R., Blamire, A., Pike, M., McKinlay, I., Stein, J., et al. (2003). Maternal neuronal antibodies associated with autism and a language disorder. Annals of Neurology, 53(4), 533–537.CrossRefPubMedGoogle Scholar
  19. Dammann, O., & O’Shea, T. M. (2008). Cytokines and perinatal brain damage. Clinics in Perinatology, 35(4), 643–663.PubMedCentralCrossRefPubMedGoogle Scholar
  20. Deykin, E. Y., & MacMahon, B. (1979). Viral exposure and autism. American Journal of Epidemiology, 109(6), 628–638.PubMedGoogle Scholar
  21. Ghaziuddin, M., Tsai, L. Y., Eilers, L., & Ghaziuddin, N. (1992). Brief report: Autism and herpes simplex encephalitis. Journal of Autism and Developmental Disorders, 22(1), 107–113.CrossRefPubMedGoogle Scholar
  22. Goines, P. E., Croen, L. A., Braunschweig, D., Yoshida, C. K., Grether, J., Hansen, R., et al. (2011). Increased mid-gestational IFN-gamma, IL-4, and IL-5 in women giving birth to a child with autism: A case-control study. Molecular Autism, 2(1), 13.PubMedCentralCrossRefPubMedGoogle Scholar
  23. Grether, J. K., Croen, L. A., Anderson, M. C., Nelson, K. B., & Yolken, R. H. (2010). Neonatally measured immunoglobulins and risk of autism. Autism Research, 3(6), 323–332.CrossRefPubMedGoogle Scholar
  24. Guinchat, V., Thorsen, P., Laurent, C., Cans, C., Bodeau, N., & Cohen, D. (2012). Pre-, peri- and neonatal risk factors for autism. Acta Obstetricia et Gynecologica Scandinavica, 91(3), 287–300.CrossRefPubMedGoogle Scholar
  25. Hallmayer, J., Cleveland, S., Torres, A., Phillips, J., Cohen, B., Torigoe, T., et al. (2011). Genetic heritability and shared environmental factors among twin pairs with autism. Archives of General Psychiatry, 68, 1095–1102.PubMedCentralCrossRefPubMedGoogle Scholar
  26. Hernan, M. A., Hernandez-Diaz, S., Werler, M. M., & Mitchell, A. A. (2002). Causal knowledge as a prerequisite for confounding evaluation: An application to birth defects epidemiology. American Journal of Epidemiology, 155(2), 176–184.CrossRefPubMedGoogle Scholar
  27. Hertz-Picciotto, I., & Delwiche, L. (2009). The rise in autism and the role of age at diagnosis. Epidemiology, 20(1), 84–90.PubMedCentralCrossRefPubMedGoogle Scholar
  28. Hsiao, E. Y., McBride, S. W., Chow, J., Mazmanian, S. K., & Patterson, P. H. (2012). Modeling an autism risk factor in mice leads to permanent immune dysregulation. Proceedings of the National Academy of Sciences of the United States of America, 109(31), 12776–12781.PubMedCentralCrossRefPubMedGoogle Scholar
  29. Hsiao, E. Y., & Patterson, P. H. (2012). Placental regulation of maternal–fetal interactions and brain development. Developmental Neurobiology, 72, 1317–1326.CrossRefPubMedGoogle Scholar
  30. Jonakait, G. M. (2007). The effects of maternal inflammation on neuronal development: Possible mechanisms. International Journal of Developmental Neuroscience, 25(7), 415–425.CrossRefPubMedGoogle Scholar
  31. Krieger, N. (1992). Overcoming the absence of socioeconomic data in medical records: Validation and application of a census-based methodology. American Journal of Public Health, 82(5), 703–710.PubMedCentralCrossRefPubMedGoogle Scholar
  32. Lord, C., Risi, S., Lambrecht, L., Cook, E. H., Jr, Leventhal, B. L., DiLavore, P. C., et al. (2000). The autism diagnostic observation schedule-generic: A standard measure of social and communication deficits associated with the spectrum of autism. Journal of Autism and Developmental Disorders, 30(3), 205–223.CrossRefPubMedGoogle Scholar
  33. Lord, C., Rutter, M., & Le Couteur, A. (1994). Autism Diagnostic Interview-Revised: A revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. Journal of Autism and Developmental Disorders, 24(5), 659–685.CrossRefPubMedGoogle Scholar
  34. Malkova, N. V., Yu, C. Z., Hsiao, E. Y., Moore, M. J., & Patterson, P. H. (2012). Maternal immune activation yields offspring displaying mouse versions of the three core symptoms of autism. Brain, Behavior, and Immunity, 26(4), 607–616.PubMedCentralCrossRefPubMedGoogle Scholar
  35. Mason-Brothers, A., Ritvo, E. R., Pingree, C., Petersen, P. B., Jenson, W. R., McMahon, W. M., et al. (1990). The UCLA-University of Utah epidemiologic survey of autism: Prenatal, perinatal, and postnatal factors. Pediatrics, 86(4), 514–519.PubMedGoogle Scholar
  36. Parker-Athill, E. C., & Tan, J. (2010). Maternal immune activation and autism spectrum disorder: Interleukin-6 signaling as a key mechanistic pathway. Neurosignals, 18(2), 113–128.PubMedCentralCrossRefPubMedGoogle Scholar
  37. Patterson, P. H. (2011). Maternal infection and immune involvement in autism. Trends in Molecular Medicine, 17, 389–394.PubMedCentralCrossRefPubMedGoogle Scholar
  38. Pinto-Martin, J. A., Levy, S. E., Feldman, J. F., Lorenz, J. M., Paneth, N., & Whitaker, A. H. (2011). Prevalence of autism spectrum disorder in adolescents born weighing <2000 grams. Pediatrics, 128(5), 883–891.PubMedCentralCrossRefPubMedGoogle Scholar
  39. Rostene, W., Kitabgi, P., & Parsadaniantz, S. M. (2007). Chemokines: A new class of neuromodulator? Nature Reviews Neuroscience, 8(11), 895–903.CrossRefPubMedGoogle Scholar
  40. 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(1), 297–302.PubMedGoogle Scholar
  41. Shi, L., Smith, S. E., Malkova, N., Tse, D., Su, Y., & Patterson, P. H. (2009). Activation of the maternal immune system alters cerebellar development in the offspring. Brain, Behavior, and Immunity, 23(1), 116–123.PubMedCentralCrossRefPubMedGoogle Scholar
  42. Short, S. J., Lubach, G. R., Karasin, A. I., Olsen, C. W., Styner, M., Knickmeyer, R. C., et al. (2010). Maternal influenza infection during pregnancy impacts postnatal brain development in the rhesus monkey. Biological Psychiatry, 67(10), 965–973.PubMedCentralCrossRefPubMedGoogle Scholar
  43. 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(40), 10695–10702.PubMedCentralCrossRefPubMedGoogle Scholar
  44. Soumiya, H., Fukumitsu, H., & Furukawa, S. (2011). Prenatal immune challenge compromises the normal course of neurogenesis during development of the mouse cerebral cortex. Journal of Neuroscience Research, 89(10), 1575–1585.CrossRefPubMedGoogle Scholar
  45. Weinberg, C. R. (1993). Toward a clearer definition of confounding. American Journal of Epidemiology, 137(1), 1–8.PubMedGoogle Scholar
  46. 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(4), 455–459.CrossRefPubMedGoogle Scholar
  47. Zerbo, O., Iosif, A. M., Walker, C., Ozonoff, S., Hansen, R. L., & Hertz-Picciotto, I. (2012). Is maternal influenza or fever during pregnancy associated with autism or developmental delays? Results from the CHARGE (CHildhood Autism Risks from Genetics and Environment) Study. Journal of Autism and Developmental Disorders, 43, 25–33.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Ousseny Zerbo
    • 1
  • Yinge Qian
    • 1
  • Cathleen Yoshida
    • 1
  • Judith K. Grether
    • 2
  • Judy Van de Water
    • 3
    • 4
    • 5
  • Lisa A. Croen
    • 1
  1. 1.Division of ResearchKaiser Permanente Northern CaliforniaOaklandUSA
  2. 2.RichmondUSA
  3. 3.Division of Rheumatology, Allergy and Clinical ImmunologyUniversity of California, DavisDavisUSA
  4. 4.The M.I.N.D. InstituteUniversity of California, DavisDavisUSA
  5. 5.The NIEHS Center for Children’s Environmental HealthUniversity of California, DavisDavisUSA

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