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, access via your institution.
Buy single article
Instant access to the full article PDF.
Price excludes VAT (USA)
Tax calculation will be finalised during checkout.
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.
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.
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.
Arndt, T. L., Stodgell, C. J., & Rodier, P. M. (2005). The teratology of autism. International Journal of Developmental Neuroscience, 23(2–3), 189–199.
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.
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.
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.
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.
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.
Braunschweig, D., & Van de Water, J. (2012). Maternal autoantibodies in autism. Archives of Neurology, 69(6), 693–699.
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.
Chess, S. (1971). Autism in children with congenital rubella. Journal of Autism and Childhood Schizophrenia, 1(1), 33–47.
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.
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.
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.
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.
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.
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.
Dammann, O., & O’Shea, T. M. (2008). Cytokines and perinatal brain damage. Clinics in Perinatology, 35(4), 643–663.
Deykin, E. Y., & MacMahon, B. (1979). Viral exposure and autism. American Journal of Epidemiology, 109(6), 628–638.
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.
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.
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.
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.
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.
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.
Hertz-Picciotto, I., & Delwiche, L. (2009). The rise in autism and the role of age at diagnosis. Epidemiology, 20(1), 84–90.
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.
Hsiao, E. Y., & Patterson, P. H. (2012). Placental regulation of maternal–fetal interactions and brain development. Developmental Neurobiology, 72, 1317–1326.
Jonakait, G. M. (2007). The effects of maternal inflammation on neuronal development: Possible mechanisms. International Journal of Developmental Neuroscience, 25(7), 415–425.
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.
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.
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.
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.
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.
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.
Patterson, P. H. (2011). Maternal infection and immune involvement in autism. Trends in Molecular Medicine, 17, 389–394.
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.
Rostene, W., Kitabgi, P., & Parsadaniantz, S. M. (2007). Chemokines: A new class of neuromodulator? Nature Reviews Neuroscience, 8(11), 895–903.
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.
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.
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.
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.
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.
Weinberg, C. R. (1993). Toward a clearer definition of confounding. American Journal of Epidemiology, 137(1), 1–8.
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.
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.
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.
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
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
- Maternal infection
- Autism spectrum disorder