Identification, Evaluation, and Management of Children With Autism Spectrum Disorder

Marcio Leyser, MD, MSc, PhD*, Fernanda JP Marques, MD, Osvaldo JM Nascimento, MD, MSc, PhD

Address correspondence to: Marcio Leyser, Division of Developmental and Behavioral Pediatrics, University of Iowa Stead Family Department of Pediatrics, 100 Hawkins Dr, 209B CDD, Iowa City, IA, USA [marcio-leyser@uiowa.edu], 319-356-8284.

We read with a strong enthusiasm the recent clinical report entitled “Identification, Evaluation, and Management of Children with Autism Spectrum Disorder”, a guidance for the Clinician in Rendering Pediatric Care, from the AAP. Developmental disabilities comprise about 15% of pediatric outpatient consults and continues to be an everyday challenge for providers working in all levels of health care1. Early diagnosis is fundamental for early intervention as it positively impacts developmental and behavioral trajectories. The etiology involved in the pathogenesis of autism is said to be multifactorial, complex and highly heterogeneous, therefore, the possibility of novel acquired causative agents for ASD in the modern era likely remains high. This warrants continuous efforts to further identify new risk factors at both clinical and research levels.

Recently, Brazil has faced an unprecedented Zika virus epidemics, followed by the observation of a new nosological category: congenital Zika syndrome2. Based on a continuous need of further advance with the knowledge about this novel congenital infectious disease, including how Zika virus exposure during the gestational period may lead to developmental disabilities, possibly including ASD, we would like to add a few points below.

Zika virus triggers a neuroimmune network, involving pro-inflammatory cytokines TNF-α and IL-6, previously related to impaired fetal brain lesions and behavioral outcomes, some of which linked to ASD3. With that in mind, infants with milder, or no symptoms of congenital Zika syndrome, but exposed to the virus during the gestational period, may be considered at risk for behavioral disorders. In brief, Zika virus may be considered a new etiological factor for communication and behavioral disorders in early child development, including autism4. However, the lack of previous epidemiological studies is one barrier in establishing this causal relationship.

Much has been learned about motor and cognitive impairments in Zika virus congenital infection5. In that regard, continuous research that also encompass multidisciplinary levels related to the social-emotional and social-communication domains and associated behavioral symptoms in infants exposed to Zika virus4 remains warranted. In theory, the resultant clinical and epidemiological findings could be translated into clinical practice, further empowering providers and families to better identify early red flags of autism in individuals exposed to Zika virus in utero or born the full-blown CZS. In conclusion, like with CMV and others congenital infectious diseases, the authors suggest that prenatal exposure to Zika virus should be also considered a prenatal risk factor for ASD.

References
1. Olusanya, B. O., Davis, A. C., Wertlieb, D., Boo, N. Y., Nair, M. K. C., Halpern, R., ... & Halfon, N. (2018). Developmental disabilities among children younger than 5 years in 195 countries and territories, 1990–2016: a systematic analysis for the global burden of disease study 2016. The Lancet Global Health, 6(10), e1100-e1121.
2. Leyser, M., Marques, F. J., & Nascimento, O. J. (2019). A multilevel-based research framework on congenital Zika syndrome. Pediatric research, 1.
3. Vianna, P., do Amaral Gomes, J., Boquett, J. A., Fraga, L. R., Schuch, J. B., Vianna, F. S. L., & Schuler-Faccini, L. (2018). Zika virus as a possible risk factor for autism spectrum disorder: neuroimmunological aspects. Neuroimmunomodulation, 25(5-6), 320-327.
4. Wheeler, A. C. (2018). Development of infants with congenital Zika syndrome: what do we know and what can we expect? Pediatrics, 141(Supplement 2), S154-S160.
5. Marques, F. J., Teixeira, M. C., Barra, R. R., de Lima, F. M., Dias, B. L. S., Pupe, C., ... & Leyser, M. (2018). Children Born with Congenital Zika Syndrome Display Atypical Gross Motor Development and a Higher Risk for Cerebral Palsy. Journal of child neurology, 0883073818811234.