Neonatal chemokine markers predict subsequent diagnosis of autism spectrum disorder and delayed development

Abstract

Immune dysregulation has been found to be related to a diagnosis of autism spectrum disorder (ASD). However, investigations in very early childhood examining immunological abnormalities such as altered neonatal cytokine/chemokine profiles in association with an aberrant developmental trajectory, are sparse. We assessed neonatal blood spots from 398 children, including 171 with ASD, which were subdivided according to severity (121 severe, 50 mild/moderate) and cognitive/adaptive levels (144 low-functioning, 27 typical to high-functioning). The remainder were 69 children with developmental delay (DD), and 158 with typical development (TD), who served as controls in the Childhood Autism Risks from Genetics and the Environment (CHARGE) study. Exploratory analysis suggested that, in comparisons with TD and DD, CTACK (CCL27) and MPIF-1 (CCL23), respectively, were independently associated with ASD. Higher neonatal levels of CTACK were associated with decreased odds of ASD compared to TD (odds ratio [OR] = 0.40, 95% confidence interval [Cl] 0.21, 0.77), whereas higher levels of MPIF-1 were associated with increased odds of ASD (OR = 2.38, 95% Cl 1.42, 3.98) compared to DD but not to TD. MPIF-1 was positively associated with better scores in several developmental domains. Dysregulation of chemokine levels in early life can impede normal immune and neurobehavioral development, which can lead to diagnosis of ASD or DD. This study collectively suggests that certain peripheral chemokines at birth are associated with ASD progression during childhood and that children with ASD and DD have distinct neonatal chemokine profiles that can differentiate their diagnoses.

Keywords: Autism spectrum disorder; Delayed development; Neonatal blood spot; Neonatal chemokines; Neonatal cytokines; Neurodevelopment.