Autism After Infection, Febrile Episodes, and Antibiotic Use During Pregnancy: An Exploratory Study

Departments of Public Health, Section of Epidemiology and.
PEDIATRICS (Impact Factor: 5.47). 11/2012; 130(6). DOI: 10.1542/peds.2012-1107
Source: PubMed


Results of animal studies suggest that maternal immune activation during pregnancy causes deficiencies in fetal neurodevelopment. Infectious disease is the most common path to maternal immune activation during pregnancy. The goal of this study was to determine the occurrence of common infections, febrile episodes, and use of antibiotics reported by the mother during pregnancy and the risk for autism spectrum disorder (ASD) and infantile autism in the offspring.

We used a population-based cohort consisting of 96 736 children aged 8 to 14 years and born from 1997 to 2003 in Denmark. Information on infection, febrile episodes, and use of antibiotics was self-reported through telephone interviews during pregnancy and early postpartum. Diagnoses of ASD and infantile autism were retrieved from the Danish Psychiatric Central Register; 976 children (1%) from the cohort were diagnosed with ASD.

Overall, we found little evidence that various types of mild common infectious diseases or febrile episodes during pregnancy were associated with ASD/infantile autism. However, our data suggest that maternal influenza infection was associated with a twofold increased risk of infantile autism, prolonged episodes of fever caused a threefold increased risk of infantile autism, and use of various antibiotics during pregnancy were potential risk factors for ASD/infantile autism.

Our results do not suggest that mild infections, febrile episodes, or use of antibiotics during pregnancy are strong risk factors for ASD/infantile autism. The results may be due to multiple testing; the few positive findings are potential chance findings.

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Available from: Hjördís Osk Atladóttir, Apr 12, 2014
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    • "Early life immune activation (e.g. infectious disease during pregnancy) is associated with a threefold increase in the risk of ASD (Atladóttir et al., 2012). Several studies have also described immune dysfunction in patients with ASD ranging from alterations of immune markers in blood to increased microglia activation in the central nervous system (CNS) (Hsiao, 2013). "
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    ABSTRACT: The pathogenesis of autism spectrum disorder (ASD) is unknown, and the immune system has been appointed to play an important role. The interleukin 33 (IL-33), a member of the IL-1, may act as an alarmin. This study aimed to evaluate plasma levels of IL-33, sST2, and IL-1β in 30 patients with ASD in comparison with 18 controls matched by gender, age and maternal age at childbirth. Patients did not differ from controls in IL-33, sST2, and IL-1β plasma levels. Alarmin levels were not correlated with age, and neither was influenced by clinical parameters. Our results undermine the role of IL-33/ST2 in ASD. Copyright © 2014 Elsevier B.V. All rights reserved.
    Journal of Neuroimmunology 01/2015; 278C:69-72. DOI:10.1016/j.jneuroim.2014.11.021 · 2.47 Impact Factor
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    • "Research studies indicate an association between viral or bacterial infections in expectant mothers and their ASD offspring (136, 137). Maternal antibodies cross the underdeveloped blood brain barrier of the fetus (138) leading to impaired fetal neurodevelopment and long-term neurodegeneration, neurobehavioral, and cognitive difficulties (139). "
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    ABSTRACT: Autism spectrum disorders (ASDs) are complex, heterogeneous disorders caused by an interaction between genetic vulnerability and environmental factors. In an effort to better target the underlying roots of ASD for diagnosis and treatment, efforts to identify reliable biomarkers in genetics, neuroimaging, gene expression, and measures of the body's metabolism are growing. For this article, we review the published studies of potential biomarkers in autism and conclude that while there is increasing promise of finding biomarkers that can help us target treatment, there are none with enough evidence to support routine clinical use unless medical illness is suspected. Promising biomarkers include those for mitochondrial function, oxidative stress, and immune function. Genetic clusters are also suggesting the potential for useful biomarkers.
    Frontiers in Psychiatry 08/2014; 5:100. DOI:10.3389/fpsyt.2014.00100
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    • "Based on a large Danish cohort (N = 1.6 million), Atladóttir et al., 2010 found that maternal viral and bacterial infection (specifically respiratory infection) during the first trimester increased the risk of ASD in the offspring by two and three-fold, respectively [12]. The same group also reported that a febrile episode lasting more than seven days increased the risk of infantile autism by three-fold in the first trimester and four-fold in the second trimester [13]. In a separate study based on a large Finnish cohort (N = 1.2 million), an increased level of maternal C-reactive protein, a biomarker for inflammation, was shown to be significantly associated with ASD diagnosis in the offspring [14]. "
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    ABSTRACT: Autism spectrum disorders are neurodevelopmental disorders characterized by two core symptoms; impaired social interactions and communication, and ritualistic or repetitive behaviors. Both epidemiological and biochemical evidence suggests that a subpopulation of autistics may be linked to immune perturbations that occurred during fetal development. These findings have given rise to an animal model, called the "maternal immune activation" model, whereby the offspring from female rodents who were subjected to an immune stimulus during early or mid-pregnancy are studied. Here, C57BL/6 mouse dams were treated mid-gestation with saline, lipopolysaccharide (LPS) to mimic a bacterial infection, or polyinosinic:polycytidylic acid (Poly IC) to mimic a viral infection. Autism-associated behaviors were examined in the adult offspring of the treated dams. Behavioral tests were conducted to assess motor activity, exploration in a novel environment, sociability, and repetitive behaviors, and data analyses were carried independently on male and female mice. We observed a main treatment effect whereby male offspring from Poly IC-treated dams showed reduced motor activity. In the marble burying test of repetitive behavior, male offspring but not female offspring from both LPS and Poly IC-treated mothers showed increased marble burying. Our findings indicate that offspring from mothers subjected to immune stimulation during gestation show a gender-specific increase in stereotyped repetitive behavior.
    PLoS ONE 08/2014; 9(8):e104433. DOI:10.1371/journal.pone.0104433 · 3.23 Impact Factor
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