An Exploratory Examination of Neonatal Cytokines and Chemokines as Predictors of Autism Risk

The Early Markers for Autism Study

Luke S. Heuer, Lisa A. Croen, Karen L. Jones, Cathleen K. Yoshida, Robin L Hansen, Robert Yolken, Ousseny Zerbo, Gerald DeLorenze, Martin Kharrazi, Paul Ashwood, Judith A Van de Water

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: The identification of an early biomarker for autism spectrum disorder (ASD) would improve the determination of risk, leading to earlier diagnosis and, potentially, earlier intervention and improved outcomes. Methods: Data were generated from the Early Markers for Autism study, a population-based case-control study of prenatal and neonatal biomarkers of ASD. Newborn bloodspots of children with ASD (n = 370), children with developmental delay (n = 140), and general population (GP) controls (n = 378) were analyzed for 42 different immune markers using a Luminex multiplex platform. Comparisons of immune marker concentrations between groups were examined using logistic regression and partial least squares discriminant analysis. Results: Children with ASD had significantly increased neonatal levels of interleukin-6 (IL-6) and IL-8 compared with GP controls. An increase in IL-8 was especially significant in the ASD group with early onset compared with the GP group, with an adjusted odds ratio of 1.97 (95% confidence interval, 1.39–2.83; p = .00014). In addition, children with ASD had significantly elevated levels of eotaxin-1, interferon-γ, and IL-12p70 relative to children with developmental delay. We observed no significant differences in levels of immune markers between the developmental delay and GP groups. Conclusions: Elevated levels of some inflammatory markers in newborn bloodspots indicated a higher degree of immune activation at birth in children who were subsequently diagnosed with ASD. The data from this exploratory study suggest that with further expansion, the development of neonatal bloodspot testing for cytokine/chemokine levels might lead to the identification of biomarkers that provide an accurate assessment of ASD risk at birth.

Original languageEnglish (US)
JournalBiological Psychiatry
DOIs
StatePublished - Jan 1 2019

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Autistic Disorder
Chemokines
Cytokines
Biomarkers
Population Control
Interleukin-8
Population Groups
Chemokine CCL11
Parturition
Newborn Infant
Autism Spectrum Disorder
Discriminant Analysis
Least-Squares Analysis
Interferons
Case-Control Studies
Early Diagnosis
Interleukin-6
Logistic Models
Odds Ratio
Confidence Intervals

Keywords

  • Autism
  • Bloodspot
  • Chemokine
  • Cytokine
  • Developmental delay
  • Neonatal

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

An Exploratory Examination of Neonatal Cytokines and Chemokines as Predictors of Autism Risk : The Early Markers for Autism Study. / Heuer, Luke S.; Croen, Lisa A.; Jones, Karen L.; Yoshida, Cathleen K.; Hansen, Robin L; Yolken, Robert; Zerbo, Ousseny; DeLorenze, Gerald; Kharrazi, Martin; Ashwood, Paul; Van de Water, Judith A.

In: Biological Psychiatry, 01.01.2019.

Research output: Contribution to journalArticle

Heuer, Luke S. ; Croen, Lisa A. ; Jones, Karen L. ; Yoshida, Cathleen K. ; Hansen, Robin L ; Yolken, Robert ; Zerbo, Ousseny ; DeLorenze, Gerald ; Kharrazi, Martin ; Ashwood, Paul ; Van de Water, Judith A. / An Exploratory Examination of Neonatal Cytokines and Chemokines as Predictors of Autism Risk : The Early Markers for Autism Study. In: Biological Psychiatry. 2019.
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abstract = "Background: The identification of an early biomarker for autism spectrum disorder (ASD) would improve the determination of risk, leading to earlier diagnosis and, potentially, earlier intervention and improved outcomes. Methods: Data were generated from the Early Markers for Autism study, a population-based case-control study of prenatal and neonatal biomarkers of ASD. Newborn bloodspots of children with ASD (n = 370), children with developmental delay (n = 140), and general population (GP) controls (n = 378) were analyzed for 42 different immune markers using a Luminex multiplex platform. Comparisons of immune marker concentrations between groups were examined using logistic regression and partial least squares discriminant analysis. Results: Children with ASD had significantly increased neonatal levels of interleukin-6 (IL-6) and IL-8 compared with GP controls. An increase in IL-8 was especially significant in the ASD group with early onset compared with the GP group, with an adjusted odds ratio of 1.97 (95{\%} confidence interval, 1.39–2.83; p = .00014). In addition, children with ASD had significantly elevated levels of eotaxin-1, interferon-γ, and IL-12p70 relative to children with developmental delay. We observed no significant differences in levels of immune markers between the developmental delay and GP groups. Conclusions: Elevated levels of some inflammatory markers in newborn bloodspots indicated a higher degree of immune activation at birth in children who were subsequently diagnosed with ASD. The data from this exploratory study suggest that with further expansion, the development of neonatal bloodspot testing for cytokine/chemokine levels might lead to the identification of biomarkers that provide an accurate assessment of ASD risk at birth.",
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T1 - An Exploratory Examination of Neonatal Cytokines and Chemokines as Predictors of Autism Risk

T2 - The Early Markers for Autism Study

AU - Heuer, Luke S.

AU - Croen, Lisa A.

AU - Jones, Karen L.

AU - Yoshida, Cathleen K.

AU - Hansen, Robin L

AU - Yolken, Robert

AU - Zerbo, Ousseny

AU - DeLorenze, Gerald

AU - Kharrazi, Martin

AU - Ashwood, Paul

AU - Van de Water, Judith A

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: The identification of an early biomarker for autism spectrum disorder (ASD) would improve the determination of risk, leading to earlier diagnosis and, potentially, earlier intervention and improved outcomes. Methods: Data were generated from the Early Markers for Autism study, a population-based case-control study of prenatal and neonatal biomarkers of ASD. Newborn bloodspots of children with ASD (n = 370), children with developmental delay (n = 140), and general population (GP) controls (n = 378) were analyzed for 42 different immune markers using a Luminex multiplex platform. Comparisons of immune marker concentrations between groups were examined using logistic regression and partial least squares discriminant analysis. Results: Children with ASD had significantly increased neonatal levels of interleukin-6 (IL-6) and IL-8 compared with GP controls. An increase in IL-8 was especially significant in the ASD group with early onset compared with the GP group, with an adjusted odds ratio of 1.97 (95% confidence interval, 1.39–2.83; p = .00014). In addition, children with ASD had significantly elevated levels of eotaxin-1, interferon-γ, and IL-12p70 relative to children with developmental delay. We observed no significant differences in levels of immune markers between the developmental delay and GP groups. Conclusions: Elevated levels of some inflammatory markers in newborn bloodspots indicated a higher degree of immune activation at birth in children who were subsequently diagnosed with ASD. The data from this exploratory study suggest that with further expansion, the development of neonatal bloodspot testing for cytokine/chemokine levels might lead to the identification of biomarkers that provide an accurate assessment of ASD risk at birth.

AB - Background: The identification of an early biomarker for autism spectrum disorder (ASD) would improve the determination of risk, leading to earlier diagnosis and, potentially, earlier intervention and improved outcomes. Methods: Data were generated from the Early Markers for Autism study, a population-based case-control study of prenatal and neonatal biomarkers of ASD. Newborn bloodspots of children with ASD (n = 370), children with developmental delay (n = 140), and general population (GP) controls (n = 378) were analyzed for 42 different immune markers using a Luminex multiplex platform. Comparisons of immune marker concentrations between groups were examined using logistic regression and partial least squares discriminant analysis. Results: Children with ASD had significantly increased neonatal levels of interleukin-6 (IL-6) and IL-8 compared with GP controls. An increase in IL-8 was especially significant in the ASD group with early onset compared with the GP group, with an adjusted odds ratio of 1.97 (95% confidence interval, 1.39–2.83; p = .00014). In addition, children with ASD had significantly elevated levels of eotaxin-1, interferon-γ, and IL-12p70 relative to children with developmental delay. We observed no significant differences in levels of immune markers between the developmental delay and GP groups. Conclusions: Elevated levels of some inflammatory markers in newborn bloodspots indicated a higher degree of immune activation at birth in children who were subsequently diagnosed with ASD. The data from this exploratory study suggest that with further expansion, the development of neonatal bloodspot testing for cytokine/chemokine levels might lead to the identification of biomarkers that provide an accurate assessment of ASD risk at birth.

KW - Autism

KW - Bloodspot

KW - Chemokine

KW - Cytokine

KW - Developmental delay

KW - Neonatal

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U2 - 10.1016/j.biopsych.2019.04.037

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