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Published on: March 2, 2018
Neonatal Cytokine Profiles Associated With Autism Spectrum Disorder
Paula Krakowiak1,2, Paula E Goines3, Daniel J Tancredi4
1Divisions of Epidemiology and of Environmental and Occupational Health, Department of Public Health Sciences, School of Medicine, University of California, Davis.
Insights
Neonatal blood tests reveal immune system differences in children later diagnosed with autism spectrum disorder (ASD). Specific cytokine profiles at birth are linked to ASD severity and nonverbal cognitive ability in males.
Area of Science:
- Neuroscience
- Immunology
- Developmental Pediatrics
Background:
- Autism spectrum disorder (ASD) is a neurodevelopmental condition diagnosed around 24 months.
- Immune system dysregulation, including altered cytokine production, is observed in children with ASD.
- Early immune markers for ASD remain largely uncharacterized.
Purpose of the Study:
- To investigate if immune dysregulation is present at birth in individuals who later develop ASD.
- To explore the association between neonatal cytokine profiles and ASD diagnosis, severity, and developmental outcomes.
Main Methods:
- Analysis of neonatal blood spots from a population-based case-control study.
- Quantification of 17 cytokines and chemokines in 214 children with ASD, 62 typically developing children, and 27 with developmental delay.
- Comparison of cytokine levels across groups and correlation with ASD symptom intensity and cognitive abilities.
Main Results:
- Elevated Interleukin (IL)-4 associated with increased odds of severe ASD.
- Elevated IL-1β associated with increased odds of mild/moderate ASD.
- In males with ASD, IL-4 negatively correlated with nonverbal cognitive ability.
Conclusions:
- Peripheral cytokine profiles at birth are associated with later ASD diagnosis and vary by ASD severity.
- Cytokine dysregulation may indicate genetic or environmental factors contributing to ASD.
- This research supports the identification of early biological markers for ASD.
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.

