The role of oxidative stress, inflammation and acetaminophen exposure from birth to early childhood in the induction of autism

Parker, William; Hornik, Chi Dang; Bilbo, Staci D.; Holzknecht, Zoie E.; Gentry, Lauren; Rao, Rasika; Lin, Song; Herbert, Martha R.; Nevison, C. D.

doi:10.1177/0300060517693423

Cited by 71 publications

(111 citation statements)

References 196 publications

(255 reference statements)

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“…It is reported that one of the most significant co morbidities associated with ASD that causes significant disability is epilepsy [28] and a number of studies have suggested that epilepsy affects a high proportion of individuals with ASD [28]. In addition, a number of risk factors for autism can be categorized as risk factors for inflammation or indicators of inflammation [28] which seems to be similar to the factors suggested in the etiology of nodding syndrome.…”

Section: Introductionmentioning

confidence: 74%

“…Although ASD is behaviorally defined, children with ASD also have many co-occurring medical conditions such as gastrointestinal abnormalities [23], seizures and epilepsy [24], attention deficits [25], anxiety disorders [26] and allergies [27]. It is reported that one of the most significant co morbidities associated with ASD that causes significant disability is epilepsy [28] and a number of studies have suggested that epilepsy affects a high proportion of individuals with ASD [28]. In addition, a number of risk factors for autism can be categorized as risk factors for inflammation or indicators of inflammation [28] which seems to be similar to the factors suggested in the etiology of nodding syndrome.…”

Section: Introductionmentioning

confidence: 99%

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Nodding Syndrome and Autism Spectrum Disorder

Kitara¹,

Arony²,

Gazda³

2019

Autism Spectrum Disorders - Advances at the End of the Second Decade of the 21st Century

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Nodding syndrome (NS) is a devastating childhood neurological disorder seen in clusters in Eastern Africa but of uncertain nosology. It is characterized by repetitive head nodding, atonic seizures, cognitive decline, and school dropout, wasting and stunted growth and it occurs in children subject to internal displacement, food insecurity, and exposure to infectious diseases, contaminated environment and with a number of repetitive behavioral abnormalities. On the other hand autism spectrum disorders (ASD) is a group of behaviorally defined neurodevelopmental disorders with lifelong consequences. They are defined by impairments in communication and social interaction along with restrictive and repetitive behaviors. It is a complex disorder associated with a wide range of disparate and seemingly unrelated factors such as; maternal exposure to various chemical substances, maternal exposure to child abuse, maternal evidence of Diabetes, autoimmune diseases, age of either parents at conception, exposure of infants to various chemical substances, low vitamin D levels of the infant at birth, gender of the infant and a large number of genetic factors. There are a number of similarities in the clinical, biochemical and behavioral findings in children with NS and ASD.

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Section: Introductionmentioning

confidence: 74%

Section: Introductionmentioning

confidence: 99%

Nodding Syndrome and Autism Spectrum Disorder

Kitara¹,

Arony²,

Gazda³

2019

Autism Spectrum Disorders - Advances at the End of the Second Decade of the 21st Century

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“…• Mercury [45][46][47][48][49][50][51][52] • Air pollution [53][54][55][56][57] • Aluminum vaccine adjuvants [2,37] • Coproporphyrin [58] • Chlorpyrifos [59] • Glyphosate [60] • Phthalates [61,62] • PBDEs [63,64] • PCBs [64,65] • Electromagnetic frequencies [66] • Industrial chemical [67,68] • Acetaminophen exposure after vaccination [69][70][71][72][73] The Numerous studies have revealed that metal toxicity is increased in individuals with ASDs [74].…”

Section: • Valproic Acidmentioning

confidence: 99%

Autism is an Acquired Cellular Detoxification Deficiency Syndrome with Heterogeneous Genetic Predisposition

Lw¹

2018

Autism Open Access

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Neurodevelopmental disorders, including autism spectrum disorders, have a complex biological and medical basis involving diverse genetic risk and myriad environmental exposures. Teasing apart the role of specific stressors is made challenging due to the large number of apparently contributing associations, gene x environment interactions and phenomimicry. Historically, these conditions have been rare, making causality assessment at the population level infeasible. Only a few vaccines have been tested for association with autism, and it has been shown that improved diagnosis only explains a percentage of the increase in diagnosis. Now the rates are so high in some countries that public school programs cannot handle to large numbers of special needs students, and professionals are quitting their jobs due to security concerns. Here, I present a mechanistic biomedical process model (theory) of the pathophysiology of autism that reconciles the apparent paradox between the high degree of causal heterogeneity in environmental toxins, the absence of common "autism genes" and the high degree of genetic concordance (heritability) of ASD and ASD-like traits. In brief, the environmental toxin sampling liability for ASD varies among families involving different local exposures following injury to normal cellular endoplasmic detoxification and mitochondrial processes from toxic metals. The literature strongly supports that autism is most accurately seen as an acquired cellular detoxification deficiency syndrome with heterogeneous genetic predisposition that manifests pathophysiologic consequences of accumulated, runaway cellular toxicity. At a more general level, it is a form of a toxicant-induced loss of tolerance of toxins, and of chronic and sustained ER overload ("ER hyperstress"), contributing to neuronal and glial apoptosis via the unfolded protein response (UPR). Inherited risk of impaired cellular detoxification and circulating metal re-toxification in neurons and glial cells accompanied by chronic UPR is key. This model explains the aberrant protein disorder observed in ASD; the great diversity of genes that are found to have low, but real contributions to ASD risk and the sensitivity of individuals with ASD to environmental toxins. The hindrance of detoxification and loss of cellular energetics leads to apoptosis, release of cytokines and chronic neuroinflammation and microglial activation, all observed hallmarks of ASD. Interference with the development of normal complex (redundant) synapses leads to a pathological variation in neuronal differentiation, axon and dendrite outgrowth, and synaptic protein expression. The most general outcomes are overall simplification of gross synaptic anatomy and, neurofunctionally, a loss of inhibitory feedback and aberrations in long-term connections between distant regions of the brain. Failed resolution of the ER stress response leads to redistribution of neurotoxic metals, and the impaired neurocellular processes lead to subsequent accumulation of a variety of additional types o...

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“…The mechanism may involve disrupted endocrine function, which has been shown in animal studies to affect fetal brain development . Another possibility is that acetaminophen disrupts brain development through dysregulation of oxidative stress …”

Section: Introductionmentioning

confidence: 99%

Associations of prenatal or infant exposure to acetaminophen or ibuprofen with mid‐childhood executive function and behaviour

Rifas‐Shiman

Cárdenas

Hivert

et al. 2019

Paediatric Perinatal Epid

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Background: Over-the-counter analgesics during pregnancy or infancy may be related to neurobehavioural problems in children, but little is known about effects of different analgesic types, dosage, and timing.Objectives: Examine associations of acetaminophen and ibuprofen use during pregnancy and infancy with executive function and behaviour problems in children. Methods:We included 1225 mother-child pairs from Project Viva, a pre-birth cohort study. We assessed prenatal acetaminophen and ibuprofen use in early and mid-pregnancy and infant use in the first year of life using questionnaires. Parents and classroom teachers assessed child behaviours in mid-childhood (median 8 years), using the Behavior Rating Inventory of Executive Function (BRIEF) and the Strengths and Difficulties Questionnaire (SDQ), with higher scores indicating worse functioning for both. We examined associations of acetaminophen and ibuprofen use during pregnancy and infancy with mid-childhood neurobehavioural outcomes using linear regression models adjusted for potential confounders.Results: During pregnancy, 46.1% of mothers used acetaminophen ≥10 times and 18.4% used any ibuprofen. In the first year, 65.3% and 39.6% of infants received acetaminophen and ibuprofen ≥6 times, respectively. Higher (≥10 vs <10 times) prenatal acetaminophen (β 1.64 points; 95% confidence interval [CI] 0.59, 2.68) and any ibuprofen (β 1.56, 95% CI 0.19, 2.92) were associated with higher parent-rated BRIEF global scores. Patterns of association were linear across categories and were similar for other parent-and teacherrated outcomes. Infancy exposure (≥6 vs <6 times) to acetaminophen (β 1.69, 95% CI 0.51, 2.87) and ibuprofen (β 1.40, 95% CI 0.25, 2.55) were associated with higher parent-rated BRIEF GEC scores but associations with teacher-rated scores were weaker.Conclusions: Prenatal and early-life exposure to acetaminophen and ibuprofen were associated with poorer executive function and behaviour in childhood. These findings highlight the need for further research on the mechanisms through which analgesics may act on fetal and child brain development. K E Y W O R D Sacetaminophen, child behaviour, child executive function, ibuprofen, infancy, pregnancy

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The role of oxidative stress, inflammation and acetaminophen exposure from birth to early childhood in the induction of autism

Cited by 71 publications

References 196 publications

Nodding Syndrome and Autism Spectrum Disorder

Nodding Syndrome and Autism Spectrum Disorder

Autism is an Acquired Cellular Detoxification Deficiency Syndrome with Heterogeneous Genetic Predisposition

Associations of prenatal or infant exposure to acetaminophen or ibuprofen with mid‐childhood executive function and behaviour

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