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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    • "Maternal infectious or inflammatory insults during pregnancy have been repeatedly implicated in the etiology of developmental neuropsychiatric disorders, including schizophrenia (Brown and Derkits, 2010; Canetta et al., 2014b), autism (Atladóttir et al., 2012; Brown et al., 2014), and bipolar disorder (Canetta et al., 2014a; Parboosing et al., 2013). Preclinical support for these epidemiological associations has been obtained by various translational rodent models demonstrating multiple brain and behavioral abnormalities following prenatal exposure to infection and/or immune activation (reviewed in Boksa (2010), Harvey and Boksa (2012), Meyer (2014), Meyer and Feldon (2010)). "
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    ABSTRACT: Prenatal exposure to infectious or inflammatory insults can increase the risk of developing neuropsychiatric disorder in later life, including schizophrenia, bipolar disorder, and autism. These brain disorders are also characterized by pre- and postsynaptic deficits. Using a well-established mouse model of maternal exposure to the viral mimetic polyriboinosinic-polyribocytidilic acid [poly(I:C)], we examined whether prenatal immune activation might cause synaptic deficits in the hippocampal formation of pubescent and adult offspring. Based on the widely appreciated role of microglia in synaptic pruning, we further explored possible associations between synaptic deficits and microglia anomalies in offspring of poly(I:C)-exposed and control mothers. We found that prenatal immune activation induced adult onset of presynaptic hippocampal deficits (as evaluated by synaptophysin and bassoon density). The early-life insult further caused postsynaptic hippocampal deficits in pubescence (as evaluated by PSD95 and SynGAP density), some of which persisted into adulthood. In contrast, prenatal immune activation did not change microglia (or astrocyte) density, nor did it alter their activation phenotypes. The prenatal manipulation did also not cause signs of persistent systemic inflammation. Despite the absence of overt glial anomalies or systemic inflammation, adult offspring exposed to prenatal immune activation displayed increased hippocampal IL-1β levels. Taken together, our findings demonstrate that age-dependent synaptic deficits and abnormal pro-inflammatory cytokine expression can occur during postnatal brain maturation in the absence of microglial anomalies or systemic inflammation.
    Brain Behavior and Immunity 09/2015; DOI:10.1016/j.bbi.2015.09.015 · 5.89 Impact Factor
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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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