Skip to main content

Advertisement

Log in

Maternal Infection During Pregnancy and Autism Spectrum Disorders

Journal of Autism and Developmental Disorders Aims and scope Submit manuscript

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).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • 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.

    Article  PubMed  Google Scholar 

  • 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 

  • 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.

    Article  PubMed Central  PubMed  Google Scholar 

  • Arndt, T. L., Stodgell, C. J., & Rodier, P. M. (2005). The teratology of autism. International Journal of Developmental Neuroscience, 23(2–3), 189–199.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed Central  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Braunschweig, D., & Van de Water, J. (2012). Maternal autoantibodies in autism. Archives of Neurology, 69(6), 693–699.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Chess, S. (1971). Autism in children with congenital rubella. Journal of Autism and Childhood Schizophrenia, 1(1), 33–47.

    Article  PubMed  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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 

  • 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.

    Article  PubMed  Google Scholar 

  • Dammann, O., & O’Shea, T. M. (2008). Cytokines and perinatal brain damage. Clinics in Perinatology, 35(4), 643–663.

    Article  PubMed Central  PubMed  Google Scholar 

  • Deykin, E. Y., & MacMahon, B. (1979). Viral exposure and autism. American Journal of Epidemiology, 109(6), 628–638.

    PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed Central  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed Central  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Hertz-Picciotto, I., & Delwiche, L. (2009). The rise in autism and the role of age at diagnosis. Epidemiology, 20(1), 84–90.

    Article  PubMed Central  PubMed  Google Scholar 

  • 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.

    Article  PubMed Central  PubMed  Google Scholar 

  • Hsiao, E. Y., & Patterson, P. H. (2012). Placental regulation of maternal–fetal interactions and brain development. Developmental Neurobiology, 72, 1317–1326.

    Article  PubMed  Google Scholar 

  • Jonakait, G. M. (2007). The effects of maternal inflammation on neuronal development: Possible mechanisms. International Journal of Developmental Neuroscience, 25(7), 415–425.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed Central  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed Central  PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    Article  PubMed Central  PubMed  Google Scholar 

  • Patterson, P. H. (2011). Maternal infection and immune involvement in autism. Trends in Molecular Medicine, 17, 389–394.

    Article  PubMed Central  PubMed  Google Scholar 

  • 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.

    Article  PubMed Central  PubMed  Google Scholar 

  • Rostene, W., Kitabgi, P., & Parsadaniantz, S. M. (2007). Chemokines: A new class of neuromodulator? Nature Reviews Neuroscience, 8(11), 895–903.

    Article  PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    Article  PubMed Central  PubMed  Google Scholar 

  • 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.

    Article  PubMed Central  PubMed  Google Scholar 

  • 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.

    Article  PubMed Central  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Weinberg, C. R. (1993). Toward a clearer definition of confounding. American Journal of Epidemiology, 137(1), 1–8.

    PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  Google Scholar 

Download references

Acknowledgments

The authors would like to thank Dr. Kaht Dorward, MD, from the department of Obstetrics and Gynecology at Kaiser Permanente San Francisco for her input on maternal infections during pregnancy. This study was funded by grants from the Centers for Disease Control and Prevention, (U10/CCU920392), the Kaiser Foundation Research Institute, and Autism Speaks.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ousseny Zerbo.

Additional information

Judith K. Grether was formerly with Environmental Health Investigations Branch, California Department of Public Health, Richmond, CA, 94804, USA.

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

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zerbo, O., Qian, Y., Yoshida, C. et al. Maternal Infection During Pregnancy and Autism Spectrum Disorders. J Autism Dev Disord 45, 4015–4025 (2015). https://doi.org/10.1007/s10803-013-2016-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10803-013-2016-3

Keywords

Navigation