Presentation on theme: "Gastrointestinal Disorders of Children with Autistic Spectrum Disorders Joseph Levy, M.D. Professor of Clinical Pediatrics Director, Program in Neurogastroenterology."— Presentation transcript:
1Gastrointestinal Disorders of Children with Autistic Spectrum Disorders Joseph Levy, M.D.Professor of Clinical Pediatrics Director, Program in NeurogastroenterologyColumbia University Medical CenterMorgan Stanley Children’s Hospital of NY Presbyterian
2Outline and GoalsReview the GI and nutritional issues impacting on the health of children on the autism spectrumPrepare parents and professionals to critically appraise the pertinent information…or how much can we trust anecdotes?Propose guidelines for assessing adequacy of nutritional intake and the need for supplements
3Autistic Spectum Disorders Social interactionVerbal and nonverbal communicationRepetitive behaviors or interests? GI disorders
5GI symptoms in ASDDo children with ASD really have more gastrointestinal symptoms than other children?Lack of published rigorous data that show increased GI symptoms in children with ASD
6Prevalence of GI symptoms: A Little Perspective Gastrointestinal complaints are very common in children with normal development:Constipation rates 16%-37%Cow’s milk protein intolerance % of otherwise normal infantsLoening-Baucke, NEJM 1998
7Prevalence of GI symptoms There is very little reliable information about whether GI symptoms are part of ASD.Bias:SelectionReferralRecall
8Prevalence of GI symptoms Retrospective survey comparing 412 children with ASD and 43 siblings:85.3% ASD had at least one GI symptom compared to 28.6% siblings.Horvath & Perman, Current Gast Reports 2002a, Current Op Ped 2002
9Prevalence of GI symptoms Survey of 500 parents:50% reported daily loose stools or frequent diarrhea33% abdominal pain20% more than 3 stools a dayNo control group, no note of selection criteriaLightdale, Siegel & Heyman, Clin Perspect Gast, 2001
10Prevalence of GI symptoms Review of medical histories of 285 children with PDD, 48 non-autistic siblings, and 102 unrelated controls:19% of children with PDD had constipation19% diarrhea, 7% alternating constipation/diarrhea.<10% controls had diarrhea or constipation.Melmed, Schneider, Fabes, Phillips & Reichelt, J Ped Gastro & Nut, 2000
11Prevalence of GI symptoms: Asking a few questions goes a long way… How was the survey developed?How were the patients selected?Was information obtained from the parents or from medical records?What was the working definition of ‘diarrhea’ and ‘constipation’ ?
12Prevalence of GI symptoms: A matter of timing Case-controlled study from UK evaluated the frequency of GI complaints before ASD was diagnosed:Exactly the same percentage (9%) of autistic and normally developing children had GI symptoms before the date of diagnosis.Black, Kaye & Jick, Brit Med J, 2002
13Prevalence of GI symptoms in ASD vs. Controls Most recent study compared 50 ASD children with 50 having other developmental delays (DD) and 50 with normal development:History of GI symptoms:70% ASD28% Normal Children42% Other DDValicenti-McDermott, McVicar, Rapin, et al. J Dev Behav Pediatr, 2006
14Prevalence of GI symptoms in ASD vs. Controls Abnormal stooling pattern:18% ASD4% Normal2% DDFood selectivity:60% ASD22% Normal36% DD
15Prevalence of GI symptoms in ASD vs. Controls Limitations of this study:Relies on family reports of symptoms(recall bias)
16Prevalence of GI symptoms: It’s all over! Most of the data published regarding GI symptoms is derived from parental recall or medical recordsPlaces the prevalence of GI symptom somewhere between…17%-86%!(Erickson, Stigler, Corkins, et al, J Autism & Dev Disorders, 2005)
17What Triggers GI Symptoms? Immaturity of the nerves and muscles responsible for moving food alongEnzyme deficienciesMalabsorption of nutrients (sugars, fats, proteins)Immune-mediated inflammation and damage
20Sources of Intestinal Pain Overstretching of muscles (gas, spastic contractions)Acid-mediated irritation of esophagus (GERD)Hypersensitive “second brain” (The brain in the gut or the ENS)Abnormal blood flow
21Consequences of GI Dysfunction Acute and chronic painInterference with consumption of adequate nutrientsAversive conditioningsFood intolerance and protein allergyLimited food choicesAbnormal stooling patterns
22Diet and NutritionRepetitive behaviors and insistence on sameness in ASD can have negative effect on dietLimited food choices is frequent complaint of families with autistic childrenA higher incidence of pica has also been noted by parents of autistic children
24Diet and NutritionNutritional status has been evaluated by several small controlled and uncontrolled studiesOverall, it appears their nutrition is adequateSelectivity does not result in malnutritionRaiten &Massaro, J Autism and Dev Disorders, 1986;Shearer, et al, J Autism and Dev Disorders, 1982;Ahearn et al, J Autism and Dev Disorders, 2001;Field & Williams, J Ped Child Health, 2003
25Food Intolerance and Allergy Anecdotal reports from parents of children with ASDMost report intolerance forcow’s milk (casein protein) orwheat (gluten protein)
26Food Intolerance and Allergy In 1971 investigators reported a case of a child with ASD and celiac disease:Autistic behaviors worsened when exposed to gluten after a period with gluten-free diet(Goodwin, Cowen & Goodwin, J Autism Child Schizophrenia, 1971)
27Food Intolerance and Allergy This case inspired a study which measured trancephalic direct current (TDC) in children with ASD and GI symptoms:ASD children showed inhibition of frontal voltage in response to 1 g PO dose gliadinNo inhibition with 1 g sugarSiblings and normal controls showed no response to either gliadin or sugar“Gluten has a direct effect on the central nervous system”TDCs: slowly changing voltages recorded from the surface of the head and originating from the cortex of the brain.Goodwin, Cowen & Goodwin, J Autism Child Schizophrenia, 1971
28Another source of biasAll the ASD children in study had previous GI complaints.Error:Generalizing differences found in a subset of childrenDo all children with ASD have changes in response to a gluten challenge?We do not know
29Food Intolerance and Allergy Long-term prospective study of gluten and milk-free diet in children with abnormal urinary peptide levels:15 children in first report, original new participants in second reportBehavioral improvement noted by parents and teachers in both reportsUrine peptide levels normalized by one yearReichelt, et al. J App Nutr, 1990Reichelt, et al. Brain Dysfunction, 1991
30Food Intolerance and Allergy Another study with 15 participants:Improved behavior and communication after 1 and 4 year periodsAlso limited to ASD children with abnormal urinary peptides; no control groupNone of the studies controlled for concomitant educational or other behavioral interventions that could have caused improvement
31Food Intolerance and Allergy Single study with control group and blinded evaluators:Found significant improvement in social abilities, cognition and attention after 1 yearKnivsberg, et al, Scan J Edu & Research, 1995Knivsberg et al, Nutri Neurosci 2002
32Food Intolerance and Allergy Most studies of gluten and/or casein-free diets have included only children with abnormal urine peptide levelsCannot generalize to all children with ASDLittle evidence that dietary protein intolerance is more prevalence in ASD populationSmall sample size, lack of control group also make the studies hard to interpret.
33The Leaky Gut Hypothesis Based on the observations that autistic behaviors improved on dietary protein-free dietsTheory is that a ‘leaky’ intestinal mucosa allows foods to enter the bloodstream.
34The Leaky Gut Hypothesis Digestion of gluten and casein releases short chain peptides which are similar to endorphins.These peptides are called ‘exorphins’Wheat products gliadomorphinsMilk protein caseomorphinsZioudrou, Streaty, Klee. J Biol Chem. 1979
38The Leaky Gut Hypothesis Orally administered gluten fragments have been detected in rat brainsOpiate receptors in brain bind gluten exorphinsCasein exorphins infused into bloodstream of rats activates the rat brain.Dohan, Adv Biochem Psychopharmocol, 1980; Hemmings, Proc Roy Coc London Ser B, 1978)
39The Leaky Gut Hypothesis Hypothesis: Gliadomorphins and casomorphins from partially digested gluten and casein are:Absorbed through a leaky gutEnter the CNSInterfere with normal brain function by mimicking the opioid hormone beta-endorphin.
41LNH: What does it supposed to mean?... Enhanced activation of lymphoid tissue in the intestineTriggered by food or viral antigensCausing an inflammatory reactionResulting in increased permeability and a leaky gut
42Lessons Learned Future Directions and Challenges ASD and the GI Tract:Lessons LearnedFuture Directions and Challenges
43Getting It Right: Commonsense Principles No two ASD/PDD children are exactly alikeGeneralizing is always tempting and an easier path to takeHuman behavior is controlled by a complex interplay of factors“Cookbook” recommendations are not going to benefit all childrenPushing the envelope of conventional medicine is commendable…up to a point
44Expanding Knowledge Anecdotal reports are the landmines of medicine Sound principles of science should not be sacrificed in the name of ideologiesProgress will only evolve from well gathered information and data interpretationMedical providers and families can be a powerful team…or they can easily become antagonistic aliens!
45SummaryProviding adequate nutrition to children with ASD remains a major challengeWorking close with a nutritionist or dietitian is important to avoid preventable deficiencies (or excesses)Understanding the neurobiology of autism will foster development of well founded interventions
46And Finally….To understand the proper role of GI complaints and nutritional issues impacting on the behavior of ASD children requires constant reevaluation and an open (but always critical) mind