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Neonatal Cytokine Profiles Associated With Autism Spectrum Disorder

  • Author Footnotes
    * PK and PEG contributed equally to this work.
    Paula Krakowiak
    Footnotes
    * PK and PEG contributed equally to this work.
    Affiliations
    Divisions of Epidemiology and of Environmental and Occupational Health, University of California, Davis, Davis, California

    School of Medicine, and MIND (Medical Investigations of Neurodevelopmental Disorders) Institute, University of California, Davis, Davis, California
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  • Author Footnotes
    * PK and PEG contributed equally to this work.
    Paula E. Goines
    Footnotes
    * PK and PEG contributed equally to this work.
    Affiliations
    Department of Public Health Sciences, Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, Davis, California
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  • Daniel J. Tancredi
    Affiliations
    Department of Internal Medicine, Department of Pediatrics, University of California, Davis, Davis, California
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  • Paul Ashwood
    Affiliations
    Department of Medical Microbiology and Immunology, University of California, Davis, Davis, California

    School of Medicine, and MIND (Medical Investigations of Neurodevelopmental Disorders) Institute, University of California, Davis, Davis, California
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  • Robin L. Hansen
    Affiliations
    School of Medicine, and MIND (Medical Investigations of Neurodevelopmental Disorders) Institute, University of California, Davis, Davis, California
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  • Irva Hertz-Picciotto
    Affiliations
    Divisions of Epidemiology and of Environmental and Occupational Health, University of California, Davis, Davis, California

    School of Medicine, and MIND (Medical Investigations of Neurodevelopmental Disorders) Institute, University of California, Davis, Davis, California
    Search for articles by this author
  • Judy Van de Water
    Correspondence
    Address correspondence to Judy Van de Water, Ph.D., Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, 451 Health Sciences Drive, Suite 6510, Davis, CA 95616-5270
    Affiliations
    Department of Public Health Sciences, Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, Davis, California

    School of Medicine, and MIND (Medical Investigations of Neurodevelopmental Disorders) Institute, University of California, Davis, Davis, California
    Search for articles by this author
  • Author Footnotes
    * PK and PEG contributed equally to this work.

      Abstract

      Background

      Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that can be reliably diagnosed at age 24 months. Immunological phenomena, including skewed cytokine production, have been observed among children with ASD. Little is known about whether immune dysregulation is present before diagnosis of ASD.

      Methods

      We examined neonatal blood spots from 214 children with ASD (141 severe, 73 mild/moderate), 62 children with typical development, and 27 children with developmental delay as control subjects who participated in the Childhood Autism Risks from Genetics and the Environment study, a population-based case-control study. Levels of 17 cytokines and chemokines were compared across groups and in relation to developmental and behavioral domains.

      Results

      Interleukin (IL)-1β and IL-4 were independently associated with ASD compared with typical development, although these relationships varied by ASD symptom intensity. Elevated IL-4 was associated with increased odds of severe ASD (odds ratio [OR] = 1.40, 95% confidence interval [CI], 1.03, 1.91), whereas IL-1β was associated with increased odds of mild/moderate ASD (OR = 3.02, 95% CI, 1.43, 6.38). Additionally, IL-4 was associated with a higher likelihood of severe ASD versus mild/moderate ASD (OR = 1.35, 95% CI, 1.04, 1.75). In male subjects with ASD, IL-4 was negatively associated with nonverbal cognitive ability (β = −3.63, SE = 1.33, p = .04).

      Conclusions

      This study is part of a growing effort to identify early biological markers for ASD. We demonstrate that peripheral cytokine profiles at birth are associated with ASD later in childhood and that cytokine profiles vary depending on ASD severity. Cytokines have complex roles in neurodevelopment, and dysregulated levels may be indicative of genetic differences and environmental exposures or their interactions that relate to ASD.

      Keywords

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