Acetaminophen (paracetamol) use, measles-mumps-rubella vaccination, and autistic disorder: The results of a parent survey
University of California San Diego, USA. Autism
(Impact Factor: 3.5).
06/2008; 12(3):293-307. DOI: 10.1177/1362361307089518
The present study was performed to determine whether acetaminophen (paracetamol) use after the measles-mumps-rubella vaccination could be associated with autistic disorder. This case-control study used the results of an online parental survey conducted from 16 July 2005 to 30 January 2006, consisting of 83 children with autistic disorder and 80 control children. Acetaminophen use after measles-mumps-rubella vaccination was significantly associated with autistic disorder when considering children 5 years of age or less (OR 6.11, 95% CI 1.42-26.3), after limiting cases to children with regression in development (OR 3.97, 95% CI 1.11-14.3), and when considering only children who had post-vaccination sequelae (OR 8.23, 95% CI 1.56-43.3), adjusting for age, gender, mother's ethnicity, and the presence of illness concurrent with measles-mumps-rubella vaccination. Ibuprofen use after measles-mumps-rubella vaccination was not associated with autistic disorder. This preliminary study found that acetaminophen use after measles-mumps-rubella vaccination was associated with autistic disorder.
Available from: N. V. C. Ralston
- "As a result, thimerosal was removed from all pediatric vaccines, except for some influenza vaccines, in the United States starting in 2001, but the incidence of autism continued to rise , furthering the doubts that vaccine-derived Hg exposures contributes to autism incidence. While a number of epidemiological studies do not indicate an association between thimerosal exposure and ASD [158, 159], possible associations between developmental disorders with Hg-containing vaccines  and delayed or even transgenerational influence of epigenetic changes have been suggested . Such genetic or epigenetic defects of the antioxidant enzyme system could cooperatively interact with other environmental electrophiles and make vulnerable individuals more sensitive to exposure levels that would otherwise be harmless. "
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ABSTRACT: Autism and autism spectrum disorders (ASDs) are behaviorally defined, but the biochemical pathogenesis of the underlying disease process remains uncharacterized. Studies indicate that antioxidant status is diminished in autistic subjects, suggesting its pathology is associated with augmented production of oxidative species and/or compromised antioxidant metabolism. This suggests ASD may result from defects in the metabolism of cellular antioxidants which maintain intracellular redox status by quenching reactive oxygen species (ROS). Selenium-dependent enzymes (selenoenzymes) are important in maintaining intercellular reducing conditions, particularly in the brain. Selenoenzymes are a family of ~25 genetically unique proteins, several of which have roles in preventing and reversing oxidative damage in brain and endocrine tissues. Since the brain's high rate of oxygen consumption is accompanied by high ROS production, selenoenzyme activities are particularly important in this tissue. Because selenoenzymes can be irreversibly inhibited by many electrophiles, exposure to these organic and inorganic agents can diminish selenoenzyme-dependent antioxidant functions. This can impair brain development, particularly via the adverse influence of oxidative stress on epigenetic regulation. Here we review the physiological roles of selenoproteins in relation to potential biochemical mechanisms of ASD etiology and pathology.
Available from: PubMed Central
- "Of particular interest is the evidence of genetic and acquired impairments in glutathione-associated pathways in patients with ASDs (150–152), suggesting a plausible mechanism for altered sensitivity to a wide range of environmental agents (metals, pesticides, drugs) proposed in ASDs (46, 47). Of note, acetaminophen, when given for common pediatric illnesses, may overwhelm glutathione metabolism and has been proposed as a possible trigger for ASDs (153–155). Furthermore, even brief exposures to agents that alter redox levels in cells early in development may change cellular developmental trajectory and ultimate cell fate, which may provide a plausible mechanism for neurodevelopmental alterations in ASDs (156). Overall, PPA-induced metabolic abnormalities and oxidative stress are consistent with findings from ASDs and ASD-related disorders. "
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ABSTRACT: Recent evidence suggests potential, but unproven, links between dietary, metabolic, infective, and gastrointestinal factors and the behavioral exacerbations and remissions of autism spectrum disorders (ASDs). Propionic acid (PPA) and its related short-chain fatty acids (SCFAs) are fermentation products of ASD-associated bacteria (Clostridia, Bacteriodetes, Desulfovibrio). SCFAs represent a group of compounds derived from the host microbiome that are plausibly linked to ASDs and can induce widespread effects on gut, brain, and behavior. Intraventricular administration of PPA and SCFAs in rats induces abnormal motor movements, repetitive interests, electrographic changes, cognitive deficits, perseveration, and impaired social interactions. The brain tissue of PPA-treated rats shows a number of ASD-linked neurochemical changes, including innate neuroinflammation, increased oxidative stress, glutathione depletion, and altered phospholipid/acylcarnitine profiles. These directly or indirectly contribute to acquired mitochondrial dysfunction via impairment in carnitine-dependent pathways, consistent with findings in patients with ASDs. Of note, common antibiotics may impair carnitine-dependent processes by altering gut flora favoring PPA-producing bacteria and by directly inhibiting carnitine transport across the gut. Human populations that are partial metabolizers of PPA are more common than previously thought. PPA has further bioactive effects on neurotransmitter systems, intracellular acidification/calcium release, fatty acid metabolism, gap junction gating, immune function, and alteration of gene expression that warrant further exploration. These findings are consistent with the symptoms and proposed underlying mechanisms of ASDs and support the use of PPA infusions in rats as a valid animal model of the condition. Collectively, this offers further support that gut-derived factors, such as dietary or enteric bacterially produced SCFAs, may be plausible environmental agents that can trigger ASDs or ASD-related behaviors and deserve further exploration in basic science, agriculture, and clinical medicine.
Available from: Rodney R Dietert
- "Additionally, Becker and Schultz (17) pointed out that early life acetaminophen use is a risk factor for asthma, and that a similar concern may exist for some populations of children relative to risk of autism. In a preliminary study using parental surveys, Schultz et al. (74) found that acetaminophen use, but not ibruprofen use, was associated with an elevated risk of autistic disorder. "
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ABSTRACT: Autism is a devastating childhood condition that has emerged as an increasing social concern just as it has increased in prevalence in recent decades. Autism and the broader category of autism spectrum disorders are among the increasingly seen examples in which there is a fetal basis for later disease or disorder. Environmental, genetic, and epigenetic factors all play a role in determining the risk of autism and some of these effects appear to be transgenerational. Identification of the most critical windows of developmental vulnerability is paramount to understanding when and under what circumstances a child is at elevated risk for autism. No single environmental factor explains the increased prevalence of autism. While a handful of environmental risk factors have been suggested based on data from human studies and animal research, it is clear that many more, and perhaps the most significant risk factors, remain to be identified. The most promising risk factors identified to date fall within the categories of drugs, environmental chemicals, infectious agents, dietary factors, and other physical/psychological stressors. However, the rate at which environmental risk factors for autism have been identified via research and safety testing has not kept pace with the emerging health threat posed by this condition. For the way forward, it seems clear that additional focused research is needed. But more importantly, successful risk reduction strategies for autism will require more extensive and relevant developmental safety testing of drugs and chemicals.
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