Evaluation, Diagnosis, and Treatment of Gastrointestinal Disorders in Individuals With ASDs: A Consensus Report
Harvard University1, University of Southern California2, University of Arkansas for Medical Sciences3, Boston Children's Hospital4, University of Colorado Denver5, New York University6, University of California, Davis7, Columbia University Medical Center8, Baylor College of Medicine9, State University of New York System10, Columbia University11, University of Rochester Medical Center12, Mahidol University13, University of Medicine and Dentistry of New Jersey14, Cleveland Clinic15, New York Academy of Medicine16, Children's Memorial Hospital17, University of California, Los Angeles18
TL;DR: The consensus expert opinion of the panel was that individuals with ASDs deserve the same thoroughness and standard of care in the diagnostic workup and treatment of gastrointestinal concerns as should occur for patients without ASDs.
Abstract: Autism spectrum disorders (ASDs) are common and clinically heterogeneous neurodevelopmental disorders. Gastrointestinal disorders and associated symptoms are commonly reported in individuals with ASDs, but key issues such as the prevalence and best treatment of these conditions are incompletely understood. A central difficulty in recognizing and characterizing gastrointestinal dysfunction with ASDs is the communication difficulties experienced by many affected individuals. A multidisciplinary panel reviewed the medical literature with the aim of generating evidence-based recommendations for diagnostic evaluation and management of gastrointestinal problems in this patient population. The panel concluded that evidence-based recommendations are not yet available. The consensus expert opinion of the panel was that individuals with ASDs deserve the same thoroughness and standard of care in the diagnostic workup and treatment of gastrointestinal concerns as should occur for patients without ASDs. Care providers should be aware that problem behavior in patients with ASDs may be the primary or sole symptom of the underlying medical condition, including some gastrointestinal disorders. For these patients, integration of behavioral and medical care may be most beneficial. Priorities for future research are identified to advance our understanding and management of gastrointestinal disorders in persons with ASDs.
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TL;DR: A gut-microbiome-brain connection in a mouse model of ASD is supported and a potential probiotic therapy for GI and particular behavioral symptoms in human neurodevelopmental disorders is identified.
2,507 citations
Cites background from "Evaluation, Diagnosis, and Treatmen..."
...…2013 ª2013 Elsevier Inc. 1455 B. fragilis Treatment Corrects ASD-Related Behavioral Abnormalities Studies suggest that GI issues can contribute to the development, persistence, and/or severity of symptoms seen in ASD and related neurodevelopmental disorders (Buie et al., 2010; Coury et al., 2012)....
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...with Neurodevelopmental Disorders...
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...Among several comorbidities in ASD, gastrointestinal (GI) distress is of particular interest, given its reported prevalence (Buie et al., 2010; Coury et al., 2012) and correlation with symptom severity (Adams et al., 2011)....
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1,483 citations
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14 Oct 2009
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TL;DR: Evidence supports the notion that mitochondrial dysfunction is associated with autism spectrum disorders, and suggests children with ASD have a spectrum of mitochondrial dysfunction of differing severity.
Abstract: A comprehensive literature search was performed to collate evidence of mitochondrial dysfunction in autism spectrum disorders (ASDs) with two primary objectives. First, features of mitochondrial dysfunction in the general population of children with ASD were identified. Second, characteristics of mitochondrial dysfunction in children with ASD and concomitant mitochondrial disease (MD) were compared with published literature of two general populations: ASD children without MD, and non-ASD children with MD. The prevalence of MD in the general population of ASD was 5.0% (95% confidence interval 3.2, 6.9%), much higher than found in the general population (≈ 0.01%). The prevalence of abnormal biomarker values of mitochondrial dysfunction was high in ASD, much higher than the prevalence of MD. Variances and mean values of many mitochondrial biomarkers (lactate, pyruvate, carnitine and ubiquinone) were significantly different between ASD and controls. Some markers correlated with ASD severity. Neuroimaging, in vitro and post-mortem brain studies were consistent with an elevated prevalence of mitochondrial dysfunction in ASD. Taken together, these findings suggest children with ASD have a spectrum of mitochondrial dysfunction of differing severity. Eighteen publications representing a total of 112 children with ASD and MD (ASD/MD) were identified. The prevalence of developmental regression (52%), seizures (41%), motor delay (51%), gastrointestinal abnormalities (74%), female gender (39%), and elevated lactate (78%) and pyruvate (45%) was significantly higher in ASD/MD compared with the general ASD population. The prevalence of many of these abnormalities was similar to the general population of children with MD, suggesting that ASD/MD represents a distinct subgroup of children with MD. Most ASD/MD cases (79%) were not associated with genetic abnormalities, raising the possibility of secondary mitochondrial dysfunction. Treatment studies for ASD/MD were limited, although improvements were noted in some studies with carnitine, co-enzyme Q10 and B-vitamins. Many studies suffered from limitations, including small sample sizes, referral or publication biases, and variability in protocols for selecting children for MD workup, collecting mitochondrial biomarkers and defining MD. Overall, this evidence supports the notion that mitochondrial dysfunction is associated with ASD. Additional studies are needed to further define the role of mitochondrial dysfunction in ASD.
665 citations
TL;DR: Eviologic 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 potentialrisk factors, and suggested the need for further exploration of certain prenatal nutrients, metabolic conditions, and exposure to endocrine-disrupting chemicals.
Abstract: 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...
659 citations
Cites background from "Evaluation, Diagnosis, and Treatmen..."
...However, there is not a clear consensus on the prevalence and potential causes of reported gut pathologies among children with ASD (26)....
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References
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TL;DR: The advantages of the GRADE system are explored, which is increasingly being adopted by organisations worldwide and which is often praised for its high level of consistency.
Abstract: Guidelines are inconsistent in how they rate the quality of evidence and the strength of recommendations. This article explores the advantages of the GRADE system, which is increasingly being adopted by organisations worldwide
13,324 citations
TL;DR: A system for grading the quality of evidence and the strength of recommendations that can be applied across a wide range of interventions and contexts is developed, and a summary of the approach from the perspective of a guideline user is presented.
Abstract: Users of clinical practice guidelines and other recommendations need to know how much confidence they can place in the recommendations Systematic and explicit methods of making judgments can reduce errors and improve communication We have developed a system for grading the quality of evidence and the strength of recommendations that can be applied across a wide range of interventions and contexts In this article we present a summary of our approach from the perspective of a guideline user Judgments about the strength of a recommendation require consideration of the balance between benefits and harms, the quality of the evidence, translation of the evidence into specific circumstances, and the certainty of the baseline risk It is also important to consider costs (resource utilisation) before making a recommendation Inconsistencies among systems for grading the quality of evidence and the strength of recommendations reduce their potential to facilitate critical appraisal and improve communication of these judgments Our system for guiding these complex judgments balances the need for simplicity with the need for full and transparent consideration of all important issues
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TL;DR: The NHANES results indicate continuing disparities by sex and between racial/ethnic groups in the prevalence of overweight and obesity among adults and overweight among children, using the most recent national data of height and weight measurements.
Abstract: ContextThe prevalence of overweight and obesity has increased markedly in the
last 2 decades in the United States.ObjectiveTo update the US prevalence estimates of overweight in children and
obesity in adults, using the most recent national data of height and weight
measurements.Design, Setting, and ParticipantsAs part of the National Health and Nutrition Examination Survey (NHANES),
a complex multistage probability sample of the US noninstitutionalized civilian
population, both height and weight measurements were obtained from 4115 adults
and 4018 children in 1999-2000 and from 4390 adults and 4258 children in 2001-2002.Main Outcome MeasurePrevalence of overweight (body mass index [BMI] ≥95th percentile
of the sex-specific BMI-for-age growth chart) among children and prevalence
of overweight (BMI, 25.0-29.9), obesity (BMI ≥30.0), and extreme obesity
(BMI ≥40.0) among adults by sex, age, and racial/ethnic group.ResultsBetween 1999-2000 and 2001-2002, there were no significant changes among
adults in the prevalence of overweight or obesity (64.5% vs 65.7%), obesity
(30.5% vs 30.6%), or extreme obesity (4.7% vs 5.1%), or among children aged
6 through 19 years in the prevalence of at risk for overweight or overweight
(29.9% vs 31.5%) or overweight (15.0% vs 16.5%). Overall, among adults aged
at least 20 years in 1999-2002, 65.1% were overweight or obese, 30.4% were
obese, and 4.9% were extremely obese. Among children aged 6 through 19 years
in 1999-2002, 31.0% were at risk for overweight or overweight and 16.0% were
overweight. The NHANES results indicate continuing disparities by sex and
between racial/ethnic groups in the prevalence of overweight and obesity.ConclusionsThere is no indication that the prevalence of obesity among adults and
overweight among children is decreasing. The high levels of overweight among
children and obesity among adults remain a major public health concern.
4,559 citations
TL;DR: In this paper, the authors investigated a consecutive series of children with chronic enterocolitis and regressive developmental disorder, and identified associated gastrointestinal disease and developmental regression in a group of previously normal children, which was generally associated in time with possible environmental triggers.
2,505 citations
TL;DR: It is indicated that innate neuroimmune reactions play a pathogenic role in an undefined proportion of autistic patients, suggesting that future therapies might involve modifying neuroglial responses in the brain.
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1,845 citations