An Exploratory Examination of Neonatal Cytokines and Chemokines as Predictors of Autism Risk: The Early Markers for Autism Study

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 to earlier intervention and improved outcomes. Methods Data were generated from the Early Markers for Autism (EMA) study, a population-based case-control study of prenatal and neonatal biomarkers of ASD. Newborn bloodspots of children with ASD (N=370), developmental delay (DD, N=140), and general population (GP, N=378) controls 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 IL-6 and IL-8 compared to GP controls. An increase in IL-8 was especially significant in the ASD group with early onset compared to the GP group with an adjusted odds ratio of 1.97 (95%CI 1.39-2.83 p=0.00014). In addition, children with ASD had significantly elevated levels of Eotaxin-1, IFN-γ, and IL-12p70 relative to children with developmental delay (DD). We observed no significant differences in levels of immune markers between the DD and GP groups. Conclusion 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.