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      Infections in children with autism spectrum disorder: Study to Explore Early Development (SEED) : Autism Spectrum Disorder and Infection

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          Abstract

          Immune system abnormalities have been widely reported among children with autism spectrum disorder (ASD), which may increase the risk of childhood infections. The Study to Explore Early Development (SEED) is a multisite case-control study of children aged 30-69 months, born in 2003-2006. Cases are children previously diagnosed and newly identified with ASD enrolled from education and clinical settings. Children with a previously diagnosed non-ASD developmental condition were included in the developmental delay/disorder (DD) control group. The population (POP) control group included children randomly sampled from birth certificates. Clinical illness from infection during the first 28 days ("neonatal," from medical records) and first three years of life (caregiver report) in cases was compared to DD and POP controls; and between cases with and without regression. Children with ASD had greater odds of neonatal (OR = 1.8; 95%CI: 1.1, 2.9) and early childhood infection (OR = 1.7; 95%CI: 1.5, 1.9) compared to POP children, and greater odds of neonatal infection (OR = 1.5; 95%CI: 1.1, 2.0) compared to DD children. Cases with regression had 1.6 times the odds (95%CI: 1.1, 2.3) of caregiver-reported infection during the first year of life compared to cases without regression, but neonatal infection risk and overall early childhood infection risk did not differ. Our results support the hypothesis that children with ASD are more likely to have infection early in life compared to the general population and to children with other developmental conditions. Future studies should examine the contributions of different causes, timing, frequency, and severity of infection to ASD risk. Autism Research 2019, 12: 136-146. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: We looked at infections during early childhood in relation to autism spectrum disorder (ASD). We found that children with ASD were more likely to have an infection in the first 28 days of life and before age three compared to children with typical development. Children with ASD were also more likely than children with other developmental delays or disorders to have an infection in the first 28 days of life.

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          Most cited references32

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          The Changing Epidemiology of Autism Spectrum Disorders

          Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with lifelong impacts. Genetic and environmental factors contribute to ASD etiology, which remains incompletely understood. Research on ASD epidemiology has made significant advances in the past decade. Current prevalence is estimated to be at least 1.5% in developed countries, with recent increases primarily among those without comorbid intellectual disability. Genetic studies have identified a number of rare de novo mutations and gained footing in the areas of polygenic risk, epigenetics, and gene-by-environment interaction. Epidemiologic investigations focused on nongenetic factors have established advanced parental age and preterm birth as ASD risk factors, indicated that prenatal exposure to air pollution and short interpregnancy interval are potential risk factors, and suggested the need for further exploration of certain prenatal nutrients, metabolic conditions, and exposure to endocrine-disrupting chemicals. We discuss future challenges and goals for ASD epidemiology as well as public health implications.
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            Immune mediators in the brain and peripheral tissues in autism spectrum disorder.

            Increasing evidence points to a central role for immune dysregulation in autism spectrum disorder (ASD). Several ASD risk genes encode components of the immune system and many maternal immune system-related risk factors--including autoimmunity, infection and fetal reactive antibodies--are associated with ASD. In addition, there is evidence of ongoing immune dysregulation in individuals with ASD and in animal models of this disorder. Recently, several molecular signalling pathways--including pathways downstream of cytokines, the receptor MET, major histocompatibility complex class I molecules, microglia and complement factors--have been identified that link immune activation to ASD phenotypes. Together, these findings indicate that the immune system is a point of convergence for multiple ASD-related genetic and environmental risk factors.
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              Maternal Infection During Pregnancy and Autism Spectrum Disorders.

              We conducted a nested case-control study including 407 cases and 2,075 frequency matched controls to investigate the association between maternal infections during pregnancy and risk of autism spectrum disorders (ASD). Cases, controls, and maternal infections were ascertained from Kaiser Permanente Northern California clinical databases. No overall association between diagnoses of any maternal infection during pregnancy and ASD was observed [adjusted odds ratio (ORadj) = 1.15, 95 % confidence interval (CI) 0.92-1.43]. However, women with infections diagnosed during a hospital admission (ORadj = 1.48, 95 % CI 1.07-2.04), particularly bacterial infections (ORadj = 1.58, 95 % CI 1.06-2.37), were at increased risk of delivering a child with ASD. Multiple infections during pregnancy were associated with ASD (ORadj = 1.36, 95 % CI 1.05-1.78).
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                Author and article information

                Journal
                Autism Research
                Autism Research
                Wiley
                19393792
                January 2019
                January 2019
                November 26 2018
                : 12
                : 1
                : 136-146
                Affiliations
                [1 ]Department of Epidemiology, Colorado School of Public Health; University of Colorado Anschutz Medical Campus; Aurora Colorado
                [2 ]Department of Pediatrics, School of Medicine; University of Colorado Anschutz Medical Campus; Aurora Colorado
                [3 ]Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH; National Centre for Register-based Research; Section for Epidemiology, Department of Public Health; Aarhus University; Aarhus Denmark
                [4 ]Department of Psychiatry, School of Medicine; University of Colorado Anschutz Medical Campus; Aurora Colorado
                [5 ]Kaiser Permanente Division of Research; Oakland California
                [6 ]University of Pennsylvania School of Nursing and Perelman School of Medicine; Philadelphia Pennsylvania
                [7 ]National Center on Birth Defects and Developmental Disabilities; Centers for Disease Control and Prevention; Atlanta Georgia
                [8 ]AJ Drexel Autism Institute; Drexel University; Philadelphia Pennsylvania
                [9 ]Department of Epidemiology; Johns Hopkins Bloomberg School of Public Health; Baltimore Maryland
                Article
                10.1002/aur.2012
                7197040
                30475448
                882ab694-50e0-4029-8a76-c79f394a55dd
                © 2018

                http://doi.wiley.com/10.1002/tdm_license_1.1

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