Skip to main content

Maternal Immune-Mediated Conditions, Autism Spectrum Disorders, and Developmental Delay


The maternal immune system may play a role in offspring neurodevelopment. We examined whether maternal autoimmune disease, asthma, and allergy were associated with child autism spectrum disorder (ASD) and developmental delay without autism (DD) using 560 ASD cases, 391 typically developing controls, and 168 DD cases from the CHildhood Autism Risk from Genetics and the Environment (CHARGE) study. Results from conditional logistic regression demonstrated few significant associations overall. Maternal autoimmune disease was significantly associated with a modest increase in odds of developmental disorders (combined ASD + DD; OR = 1.46, 95 % CI 1.01, 2.09) but not of ASD alone. Associations with certain allergens and onset periods were also suggested. These findings suggest maternal autoimmune disease may modestly influence childhood developmental disorders (ASD + DD).

This is a preview of subscription content, access via your institution.


  • An, B. A. (2002). Performing logistic regression on survey data with the new surveylogistic procedure. SUGI 27, SAS Institute, Inc., Cary, North Carolina, USA. Paper 258–27.

  • Atladottir, H. O., Pedersen, M. G., Thorsen, P., et al. (2009). Association of family history of autoimmune diseases and autism spectrum disorders. Pediatrics, 124(2), 687–694.

    PubMed  Article  Google Scholar 

  • Bandini, L. G., Anderson, S. E., Curtin, C., et al. (2010). Food selectivity in children with autism spectrum disorders and typically developing children. J Pediatr, 157(2), 259–264.

    PubMed Central  PubMed  Article  Google Scholar 

  • Blalock, J. E., & Smith, E. M. (2007). Conceptual development of the immune system as a sixth sense. Brain, Behavior, and Immunity, 21(1), 23–33.

    PubMed  Article  Google Scholar 

  • Boksa, P. (2010). Effects of prenatal infection on brain development and behavior: A review of findings from animal models. Brain, Behavior, and Immunity, 24(6), 881–897.

    PubMed  Article  Google Scholar 

  • Boyce, G. C., Smith, T. B., & Casto, G. (1999). Health and educational outcomes of children who experienced severe neonatal medical complications. The Journal of Genetic Psychology, 160(3), 261–269.

    PubMed  Article  Google Scholar 

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

    PubMed  Article  Google Scholar 

  • Braunschweig, D., Ashwood, P., Krakowiak, P., Hertz-Picciotto, I., Hansen, R., Croen, L. A., et al. (2008). Autism: Maternally derived antibodies specific for fetal brain proteins. Neurotoxicology, 29(2), 226–231.

    PubMed Central  PubMed  Google Scholar 

  • Braunschweig, D., Duncanson, P., Boyce, R., et al. (2012). Behavioral correlates of maternal antibody status among children with autism. Journal of Autism and Developmental Disorders, 42(7), 1435–1445.

    PubMed  Article  Google Scholar 

  • Carvalheiras, G., Faria, R., Braga, J., et al. (2012). Fetal outcome in autoimmune diseases. Autoimmunity Reviews, 11(6–7), A520–530.

    PubMed  Article  Google Scholar 

  • Comi, A. M., Zimmerman, A. W., Frye, V. H., et al. (1999). Familial clustering of autoimmune disorders and evaluation of medical risk factors in autism. Journal of Child Neurology, 14(6), 384–388.

    Article  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.

    PubMed  Article  Google Scholar 

  • Gardener, H., Spiegelman, D., & Buka, S. L. (2011). Perinatal and neonatal risk factors for autism: A comprehensive meta-analysis. Pediatrics, 128(2), 344–355.

    PubMed Central  PubMed  Article  Google Scholar 

  • Hertzmark, E., Pazaris, M., & Spiegelman, D. (2009). The SAS mediate macro. Brigham and Women’s Hospital. Boston: Channing Laboratory.

    Google Scholar 

  • Hertz-Picciotto, I., Croen, L. A., Hansen, R., Jones, C. R., van de Water, J., & Pessah, I. N. (2006). The CHARGE study: An epidemiologic investigation of genetic and environmental factors contributing to autism. Environmental Health Perspectives, 114(7), 1119–1125.

    PubMed Central  PubMed  Article  Google Scholar 

  • Jones, W. R. (1994). Autoimmune disease and pregnancy. The Australian and New Zealand Journal of Obstetrics Gynaecology, 34(3), 251–258.

    Article  Google Scholar 

  • Keil, A., Daniels, J. L., Forssen, U., et al. (2010). Parental autoimmune diseases associated with autism spectrum disorders in offspring. Epidemiology, 21(6), 805–808.

    PubMed Central  PubMed  Article  Google Scholar 

  • Kerstjens, J. M., de Winter, A. F., Bocca-Tjeertes, I. F., et al. (2012). Risk of developmental delay increases exponentially as gestational age of preterm infants decreases: A cohort study at age 4 years. Developmental Medicine and Child Neurology, 54(12), 1096–1101.

    PubMed  Article  Google Scholar 

  • Lahita, R. G. (1988). Systemic lupus erythematosus: Learning disability in the male offspring of female patients and relationship to laterality. Psychoneuroendocrinology, 13(5), 385–396.

    Google Scholar 

  • Lin, D. Y., Fleming, T. R., & De Gruttola, V. (1997). Estimating the proportion of treatment effect explained by a surrogate marker. Statistics in Medicine, 16(13), 1515–1527.

    PubMed  Article  Google Scholar 

  • Lord, C., Rutter, M., Goode, S., Heemsbergen, J., Jordan, H., Mawhood, L., et al. (1989). Autism diagnostic observation schedule: A standardized observation of communicative and social behavior. Journal of Autism and Developmental Disorders, 19(2), 185–212.

    PubMed  Article  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.

    PubMed  Article  Google Scholar 

  • McAllister, D. L., Kaplan, B. J., Edworthy, S. M., et al. (1997). The influence of systemic lupus erythematosus on fetal development: Cognitive, behavioral, and health trends. J Int Neuropsychol Soc, 3(4), 370–376.

    Google Scholar 

  • Money, J., Bobrow, N. A., & Clarke, F. C. (1971). Autism and autoimmune disease: A family study. Journal of Autism and Childhood Schizophrenia, 1(2), 146–160.

    PubMed  Article  Google Scholar 

  • Mouridsen, S. E., Rich, B., Isager, T., et al. (2007). Autoimmune diseases in parents of children with infantile autism: A case-control study. Developmental Medicine and Child Neurology, 49(6), 429–432.

    PubMed  Article  Google Scholar 

  • Mullen, E. M. (1995). The mullen scales of early learning. Circle Pines, MN: American Guidance Service Inc.

    Google Scholar 

  • Ross, G., Sammaritano, L., Nass, R., Lockshin, M. (2003). Effects of mothers' autoimmune disease during pregnancy on learning disabilities and hand preference in their children. Arch Pediatr Adolesc Med, 157(4), 397–402.

    Google Scholar 

  • Rutter, M., Bailey, A., & Lord, C. (2003). The social communication questionnaire. Los Angeles, CA: Western Psychological Services.

    Google Scholar 

  • Song, Y. W., & Kang, E. H. (2010). Autoantibodies in rheumatoid arthritis: Rheumatoid factors and anticitrullinated protein antibodies. QJM, 103(3), 139–146.

    PubMed Central  PubMed  Article  Google Scholar 

  • Sparrow, S. S., Balla, D. A., & Cicchetti, D. V. (1984). Vineland adaptive behavior scales. Bloomington, MN: Pearson Assessments.

    Google Scholar 

  • Sweeten, T. L., Bowyer, S. L., Posey, D. J., et al. (2003). Increased prevalence of familial autoimmunity in probands with pervasive developmental disorders. Pediatrics, 112(5), e420.

    PubMed  Article  Google Scholar 

  • Wootla, B., Lacroix-Desmazes, S., Warrington, A. E., et al. (2011). Autoantibodies with enzymatic properties in human autoimmune diseases. Journal of Autoimmunity, 37(2), 144–150.

    PubMed Central  PubMed  Article  Google Scholar 

  • Zaretsky, M. V., Alexander, J. M., Byrd, W., et al. (2004). Transfer of inflammatory cytokines across the placenta. Obstetrics and Gynecology, 103(3), 546–550.

    PubMed  Article  Google Scholar 

  • Zimmerman, A. W., Connors, S. L., Matteson, K. J., et al. (2007). Maternal antibrain antibodies in autism. Brain Behavior Immunity, 21(3), 351–357.

    Article  Google Scholar 

Download references


This work was supported by the following grants: National Institute of Environmental Health Sciences R01 ES015359, National Institute of Environmental Health Sciences P01 ES11269, Environmental Protection Agency STAR #R829388 & R833292, and 5-T32MH073124. The authors have no financial relationships relevant to this article or conflicts of interest to disclose.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Kristen Lyall.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 42 kb)

Appendix: List of Included Maternal Autoimmune Conditions

Appendix: List of Included Maternal Autoimmune Conditions

  1. 1.

    Addison’s disease

  2. 2.

    Adult Still’s disease

  3. 3.

    Alopecia areata

  4. 4.

    Amyotrophic lateral sclerosis (ALS)

  5. 5.

    Ankylosing spondylitis

  6. 6.

    Antiphospholipid antibody syndrome

  7. 7.

    Aplastic anemia

  8. 8.

    Autoimmune hepatitis

  9. 9.

    Autoimmune thyroid disease

  10. 10.

    Autoimmune thyroiditis

  11. 11.

    Behcet’s syndrome

  12. 12.

    Celiac disease

  13. 13.

    CREST syndrome/Scleroderma/Progressive systemic sclerosis

  14. 14.

    Crohn’s disease

  15. 15.

    Dermatitis herpetiformis

  16. 16.

    Diabetes-Type I

  17. 17.

    Discoid lupus

  18. 18.


  19. 19.

    Giant cell arteritis

  20. 20.

    Grave’s disease

  21. 21.

    Guillain–Barre syndrome

  22. 22.

    Hashimoto’s thyroiditis

  23. 23.

    Hemolytic anemia

  24. 24.

    Inflammatory bowel disease (IBD)

  25. 25.

    Idiopathic thrombocytopenic purpura (ITP)

  26. 26.

    Kawasaki syndrome

  27. 27.

    Meniere’s disease

  28. 28.

    Mixed connective tissue disease

  29. 29.

    Multiple sclerosis

  30. 30.

    Myasthenia gravis

  31. 31.

    Multiple sclerosis

  32. 32.

    Optic neuritis

  33. 33.

    Pemphigus/Pemphigus vulgaris

  34. 34.

    Pernicious anemia

  35. 35.


  36. 36.

    Primary biliary cirrhosis

  37. 37.

    Primary Sjogren’s syndrome

  38. 38.


  39. 39.

    Raynaud’s disease/phenomenon

  40. 40.

    Reiter’s syndrome/Reiter’s arthritis

  41. 41.

    Rheumatic carditis/Rheumatic heart disease

  42. 42.

    Rheumatoid arthritis (RA)

  43. 43.


  44. 44.

    Sjogren’s syndrome

  45. 45.

    Stevens-Johnson syndrome

  46. 46.

    Sydenham’s chorea

  47. 47.

    Systemic lupus erythematosus (SLE)

  48. 48.

    Systemic sclerosis/Scleroderma

  49. 49.


  50. 50.

    Thyroid disease

  51. 51.

    Tourette syndrome

  52. 52.

    Ulcerative colitis

  53. 53.


  54. 54.


Note: The most common autoimmune conditions in the study population were thyroid diseases, psoriasis, and rheumatoid arthritis; other conditions were rare and accounted for 5 % or less of autoimmune diseases reported.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Lyall, K., Ashwood, P., Van de Water, J. et al. Maternal Immune-Mediated Conditions, Autism Spectrum Disorders, and Developmental Delay. J Autism Dev Disord 44, 1546–1555 (2014).

Download citation

  • Published:

  • Issue Date:

  • DOI:


  • Autoimmune disease
  • Asthma
  • Allergy
  • Autism
  • Developmental delay
  • Maternal risk factors