C O V E R S T O R Y

Controversial issues in treating

the dental patient with autism
Robert E. Rada, DDS

utism is a develop-

A mental, neuropsychiatric
disorder that begins in
early childhood. Kanner1
first described it in 1943.
The phenotype is described in three
diagnostic behavioral domains:
impairments in social interactions,
ABSTRACT
Background. The author conducted a literature review to investigate
concerns that parents of a child with an autism spectrum disorder may
have when oral health care is provided to the child.
Types of Studies Reviewed. The author conducted a search of
PubMed using the terms “mercury,” “fluoride,” “nitrous oxide,” “antibi-
impairments in communication, and otics,” “gluten,” “casein,” “acetaminophen” and “dentistry” each with the
repetitive or restrictive behaviors.2 term “autism.” He identified controlled studies and literature reviews in
Epidemiologic studies from the both medical and alternative medical literature that were related to
early 1990s estimated that one in areas of importance to oral health care workers. The use of mercury, fluo-
1,500 children had autism. In 2002, ride, nitrous oxide, antibiotic agents and acetaminophen all are sources of
this number was one in 150.3 A controversy between dentistry and the parents of children who have
recent article stated the prevalence autism.
as roughly one in 100 children aged Results. The author found that patients who have autism frequently
3 to 17 years.4 It is not clear also have allergies, immune system problems, gastrointestinal distur-
whether this is a true increase or bances and seizures. Dental health care workers must be aware of these
related to broader and more vigilant comorbid conditions so they can provide optimal care to the children with
diagnoses. What is clear is that den- autism spectrum disorders. The author found two distinct theories as to
tists who treat children likely will what causes autism: one that focuses on genetic causes, and one that
encounter a child whose autism has focuses on the impact of the environment. He found that the interpreta-
been diagnosed. There may even be tion of these theories might affect parents’ concerns about various dental
confusion among parents that cer- treatments.
tain dental care treatments could Clinical Implications. Dentists treating patients who have autism
have adverse effects on their chil- may need to provide more than standard patient care, as the use of time-
dren who have autism. tested dental treatment and prevention modalities may be questioned or
Because of the variability in the refused by parents.
observed degree of the three Key Words. Autistic disorder; dental care for people with disabilities;
domains of autism, the disorder is special-care dentistry.
described as a spectrum. Autism JADA 2010;141(8):947-953.
spectrum disorder is divided into
various diagnostic groups: autistic Dr. Rada is a clinical associate professor, Department of Oral Medicine and Diagnostic Sciences, College
of Dentistry, University of Illinois at Chicago, and he maintains a private practice in general dentistry
disorder, Asperger syndrome and in LaGrange, Ill. Address reprint requests to Dr. Rada at 1415 W. 47th St., LaGrange, Ill. 60525, e-mail
pervasive developmental dis- “rrada@uic.edu”.

JADA, Vol. 141 http://jada.ada.org August 2010 947

Copyright © 2010 American Dental Association. All rights reserved. Reprinted by permission.
C O V E R S T O R Y

BOX 1 and “dentistry.” I also reviewed the Web sites

listed in Box 1 for links to related articles.
Organizations serving both
parents and researchers. DENTISTRY AND AUTISM

dAutism Society of America (“www.autism-society.org”) Not only do dental health care workers have to
dAutism Speaks (“www.autismspeaks.org”) address behavior management challenges when
dAutism Research Institute (“www. autism.com”) treating patients who have autism,18-20 but also
dAutismOne (“www.autismone.org”) they must be prepared to discuss family members’
concerns. Some of the controversial issues related
order–not otherwise specified. Impairments directly to the treatment of dental patients who
within the three diagnostic behavioral domains have autism are based on the biomedical and
vary within these groups.5 For the purposes of alternative medical literature. These issues may
this article, “autism” refers to the complete spec- not be well researched, but parents of children
trum and may include any of these three diag- who have autism can hold strong opinions on
nostic groups. them.
There are no biological tests for autism. Its A patient with autism seen in the dental office
diagnosis is made on the basis of the presence frequently may have multiple allergies, immune
and extent of the three domains. As a result, con- system dysfunction, gastrointestinal (GI) distur-
troversies related to autism have arisen. Re- bances, seizures, mood disorders and aggressive
searchers debate as to whether the disorder is or self-injurious behaviors.8,21-23 Many children
due to genetic defects, environmental factors or with autism are undergoing biomedical treat-
combinations of both factors.5-10 ments in an attempt to reverse the traits of
Some investigators have suggested that autism autism through integrative medicine (the combi-
has an immunological component.11-14 These inves- nation of conventional and alternative medical
tigators suggest that autism appears to be a practices).24 A parents’ group Web site includes
genetically influenced, multisystem model in anecdotal reports describing children who have
which environmental factors affect biological recovered from autism to various extents after
processes in the body or modulate gene expres- the use of alternative therapy or integrative med-
sion within the nervous system. icine.25 This has led to strong emotions and many
Many parents use environmental factors to parents’ being at odds with conventional medical
guide them in determining the course of treat- treatments. Family members may voice concerns
ment for their child who has autism.8 Numerous about the use of mercury, fluoride, nitrous oxide,
genes and biochemical pathways can be affected antibiotic agents and acetaminophen. The par-
by environmental toxins.15 Higher rates of autism ents asking about the safety of dental materials
have been found in regions of the country in and related care often are highly educated and
which there are higher levels of environmental have researched the topic. On the other hand,
pollutants.8 There is no direct proof that environ- dental health care workers may not be aware of
mental factors are the cause for this increase; these concerns, which can lead to adversity
however, some Web sites and parent organiza- between and a lack of confidence on the part of
tions believe these viewpoints are true on the both parties.
basis of anecdotal reports by parents of children
who have autism.16,17 Parents’ concerns about MERCURY
environmental toxins and their potential associa- Although dental amalgam generally is considered
tions with autism may result in their having con- to be a safe and effective restorative material,26
flicting opinions with dental practitioners when for parents of children who have autism, the use
their child requires dental treatment. of dental amalgam can be an especially sensitive
I conducted a literature review to investigate issue. The alternative medical literature suggests
concerns that parents of a child with an autism that children who have autism are genetically
spectrum disorder may have when oral health
care is provided to the child. I searched PubMed ABBREVIATION KEY. CPP-ACP: Casein
for the following terms in conjunction with phosphopeptide-amorphous calcium phosphate.
“autism”: “mercury,” “fluoride,” “nitrous oxide,” GI: Gastrointestinal. MTHFR: Methylenetetrahydro-
“antibiotics,” “gluten,” “casein,” “acetaminophen” folate reductase.

948 JADA, Vol. 141 http://jada.ada.org August 2010

Copyright © 2010 American Dental Association. All rights reserved. Reprinted by permission.
 C O V E R S T O R Y

predisposed to an inability to clear the body of be a problem for children who are susceptible to
heavy metal contaminants such as aluminum or developing dental caries.
mercury.27-30 Some children who have autism have Parents whose children eat the toothpaste or
low levels of glutathione, which is important in are not able to rinse and spit after toothbrushing
the body’s detoxification system. Mercury is an have real concerns about GI irritation and fluo-
inhibitor of glutamate transporters. Despite the rosis. Children who are not able to understand
fact that this issue needs more research to be ver- and follow directions also often swallow fluori-
ified, some children undergo biomedical chelation dated mouthwashes.34 Dentists should be aware
therapies to have these metals removed from that the parents of children who swallow tooth-
their bodies.29 paste and mouthwash may try to avert their con-
The results of an unreplicated 2007 study cerns about flouride by providing their children
showed an excess of mercury in the dental pulps with a fluoride-free dentifrice. Fluoride is a GI
of primary teeth in children with autism.31 From irritant, which can cause abdominal discomfort
the results of this study, the authors inferred that and vomiting when excessive amounts are swal-
children who have autism have an inability to lowed. With prolonged ingestion, it can damage
clear the metal. Dentists should be the gastroduodenal mucosa. Small
aware of this study and be able to children can develop fluorosis of the
discuss with family members the Family members’ permanent incisors when excessive
lack of additional research to sub- concerns about amounts of toothpaste are placed on
stantiate its conclusion. mercury can be their toothbrushes.35,36
Family members’ concerns about tempered in the Although children with develop-
mercury can be tempered in the mental disabilities are at a higher
dental office.
dental office. There are several risk of developing caries than are
restorative options that can be children in the general population,
used. Both resin-based composites and resin- children who have autism tend to have a lower
reinforced glass ionomers are viable choices. caries rate.37,38 The presence of plaque, however, is
Unfortunately, neither can withstand moisture consistently high in children who have autism.37
contamination during placement as well as dental In a sample of children with autism spectrum dis-
amalgam can. Patients with autism can have a order enrolled in Medicaid, 56 percent were pre-
difficult time keeping still, and moisture contami- scribed at least one psychotropic medication, and
nation is a distinct possibility. When providing 20 percent were prescribed three or more.39 These
information to the parents and caregivers of types of medications are known to cause xero-
patients with autism, practitioners should respect stomia, which is a risk factor in developing dental
their reasons for not wanting the patient to caries. Approximately 25 percent of children with
receive dental amalgam. However, a thorough autism have seizures.21,40 Antiseizure medications
discussion about the longevity factors associated can cause gingival overgrowth, xerostomia or
with alternative restorative materials and the both. Both of these adverse effects can make
compromising factors associated with contamina- plaque control more difficult and put the child at
tion is essential during the informed-consent greater risk of developing caries. Children who
process. crave sweets in their diets also may be more
prone to caries. All of these factors make preven-
FLUORIDE tive therapies especially important in this
Another area of concern among some parents of population.
children who have autism is the use of fluoride. Dentists should counsel parents who have con-
There is a philosophy put forth in the alternative cerns about fluoride toxicity—whether neurolog-
medical literature about avoiding fluoride use in ical or GI related—regarding the importance of
children with autism.32 Proponents of this belief plaque control for their children. These children
suggest that fluoride inhibits critical antioxidant may need to undergo prophylaxis more fre-
enzymes and has been linked to excitotoxic reac- quently, and desensitization therapy related to
tions within the brain. There are parents who toothbrushing may be necessary in particularly
believe that minimizing fluoride exposure in their resistant children.18-20 Dentists may need to con-
children with autism is an important part of bio- sult with occupational therapists to help children
medical treatment.33 This practice, however, could who have autism accept toothbrushing.

JADA, Vol. 141 http://jada.ada.org August 2010 949

Copyright © 2010 American Dental Association. All rights reserved. Reprinted by permission.
C O V E R S T O R Y

Many people with developmental disabilities dren with autism.46 However, alternative medical
experience gastroesophageal reflux disease.41,42 practitioners theorize that an inability to ade-
Fluoride can be useful in preventing enamel dis- quately metabolize gluten and casein results in a
solution caused by intraoral acidity. Dentists release of peptides that are transferred from the
should explain the preventive benefits of fluoride intestine into the bloodstream.21,23,24 These pep-
varnishes—low total fluoride exposure and high tides are said to become biologically active as they
tooth-surface concentration—to the parents. cross the blood-brain barrier and bind to opioid
receptors, leading to the abnormal behaviors
GLUTEN, CASEIN AND DENTAL MATERIALS associated with autism spectrum disorders.24 On
The results of several studies have suggested that the other hand, the authors of a literature review
GI symptoms are common comorbidities in chil- found that, on the basis of the scientific research
dren with autism spectrum disorders.23,43,44 Re- they reviewed, they did not recommend exclusion
ported symptoms include abdominal bloating, diets as standard treatment.50 Nevertheless, den-
abdominal discomfort, diarrhea and gastro- tists are likely to encounter patients who are fol-
esophageal reflux. In other children, feeding lowing special diets. If parents request confirma-
issues and food selectivity have tion about the gluten contents of
been noted. Many parents have con- dental materials, there is a Web
firmed these findings.8 However, Dentists are likely to site that contains this information
the results of a recent study showed encounter patients that dentists can consult.51 In addi-
that the overall incidence of GI who are following tion, manufacturers’ sales represen-
symptoms did not differ between special diets. tatives may know if their products
children with autism and control are gluten free.
participants.45 There also does not The use of products containing
appear to be any digestive system disorders that casein phosphopeptide-amorphous calcium phos-
are specific to autism.46 Nonetheless, many par- phate (CPP-ACP) (Recaldent, Recaldent Pty, Mel-
ents have started having their children undergo bourne, Australia) often is recommended to
various dietary interventions.24 For example, any enhance remineralization of tooth enamel. CG
suspected GI irritants are removed from the America (Alsip, Ill.) states on its Web site that
child’s diet. part of the active ingredient of Recaldent (CPP-
Autism frequently is treated with applied ACP) is milk derived and should not be used by
behavioral and occupational therapy. However, patients with milk protein allergies. GC America
when the GI problems are treated, many parents recommends that practitioners not use MI Paste
have stated that their children’s behavior also (GC America) if the patient has a confirmed or
improves.8,27,46 In light of these observations, a suspected milk protein (immunoglobulin E)
gluten-free, casein-free diet has become popular.47,48 allergy.52 Dental professionals may want to con-
The results of one study suggested that sider these facts when treating patients who have
non–immunoglobulin E-mediated food allergy, autism.
mainly against the milk protein casein, may play a
role in causing GI symptoms.49 In the alternative ANTIBIOTIC AGENTS
medical literature, antibiotic agent overuse has The relationship between autism and a defective
been related to an increase in autistic symptoms GI system is not clear.46,53 However, dental profes-
owing to intestinal damage caused by the resulting sionals may treat children with autism who are
dysbiosis in the gut. Alternative medicine practi- undergoing some type of GI treatment. Asking
tioners prescribe antifungal agents and probiotic the children’s parents questions about the chil-
agents (live microorganisms that are similar to dren’s use of probiotics is appropriate. Probiotics
beneficial microorganisms found in the human gut) are available to consumers mainly in the form of
to help patients who have autism maintain dietary supplements and foods. So as not to dis-
intestinal mucosal immune homeostasis.25,49 rupt the intestinal flora, dentists should be espe-
For some patients, these special diets may cially judicious when prescribing antibiotic
affect preventive dental treatment. For example, agents, since they may affect the balance of
parents may ask if the prophylaxis paste is gluten microorganisms in the intestines.5,24,27 Dentists
19
free. There is a lack of scientific evidence on the may want to consult with the patient’s medical
benefits of gluten-free or casein-free diets for chil- practitioner before writing a prescription.

950 JADA, Vol. 141 http://jada.ada.org August 2010

Copyright © 2010 American Dental Association. All rights reserved. Reprinted by permission.
 C O V E R S T O R Y

ACETAMINOPHEN with vitamin B12 deficiency also are at risk of

experiencing morbidity or mortality.59 The chil-
There is one unsubstantiated study with results dren who died underwent lengthy medical pro-
that suggest that acetaminophen use after cedures under general anesthesia in the oper-
receiving a measles, mumps and rubella vaccine ating room.58
54
could be associated with autistic disorder. This I did not find any articles in the literature that
association was not found in children who were specifically stated that nitrous oxide use should
given ibuprofen. Sulfation is the primary pathway be avoided in children with autism. However,
for acetaminophen metabolism in children some children with autism have biochemical
through age 10 or 12 years. There may be a sulfa- abnormalities in folic acid metabolism, vitamin
tion deficit in some children with autism, which B12 deficiencies and the dysfunction of
can allow the toxic metabolite N-acetyl-p- MTHFR.30,60 Concerns about deficient biochemical
55
bezoquinoneimine to accumulate. This toxic pathways are found in autism-related forums on
metabolite may interfere with the immune the Internet, and some parents may be wary of
system or have direct neurotoxic effects.53 I did nitrous oxide’s being used to sedate their child.
not find any studies in the litera- Dentists should be aware of the rea-
ture with results that suggested sons for the parents’ concerns and
Dentists should be
that acetaminophen is inappro- be able to help them make informed
priate for children with autism who aware of the reasons decisions. Certainly the risk of
are experiencing oral pain. How- for the parents’ using nitrous oxide is small, if not
ever, recommending this medica- concerns and be able nonexistent.56 The dentist could use
tion may be of concern to some par- to help them make another method of sedation or have
ents, and ibuprofen can be informed decisions. the patient undergo additional pre-
recommended as an alternative. anesthesia testing for the gene defi-
ciency, as well as consult with the
NITROUS OXIDE patient’s medical providers, if the parents are
Another controversial issue is related to the use strongly opposed to the use of nitrous oxide.56
56
of nitrous oxide. Some dentists might find the
use of nitrous oxide useful in calming apprehen- CONCLUSIONS
sive children. The authors of two studies recom- Autism treatment and research have been sepa-
mend the use of nitrous oxide for dental patients rate entities. Children with autism need help now
who have mild behavioral issues associated with and cannot wait for research to be conducted and
autism.18,19 The authors of another study suggest treatment to be developed.23,27 Thus, there is some
that the use of nitrous oxide would not be valu- confusion as to which treatments are appropriate.
able for dentists who instead use effective Several organizations are trying to bring parents
behavior guidance techniques recognized by the and researchers together (Box 1). These organiza-
American Academy of Pediatric Dentistry.57 There tions disseminate information about, but do not
is even a recommendation that certain people all agree with treatment approaches recom-
who have autism not receive nitrous oxide anes- mended by, conventional medicine. They do, how-
thesia owing to the potential for serious systemic ever, disseminate much of the information about
adverse effects.58 both conventional and alternative treatments
Nitrous oxide inhibits the enzyme methylene- that parents discuss with dental practitioners. It
tetrahydrofolate reductase (MTHFR), which can would be helpful for dental health care workers to
limit the synthesis of DNA severely, causing mag- read these Web sites’ content or attend the orga-
aloblastic changes in blood cells and bone nizations’ conferences to learn more about the dis-
marrow. In healthy, neurotypical patients, there order and its effect on families. The people
generally is no problem when DNA synthesis is speaking at and attending these conferences are
inhibited, and MTHFR is synthesized quickly. passionate about the subject. However, it can be
However, there are case reports describing the difficult for clinicians and parents to separate the
death of children with a specific genetic enzyme science from the pseudoscience presented at these
deficiency involved in these chemical path- meetings.
ways.58,59 The enzyme is MTHFR, which is in- As there is a reported increase in the preva-
volved with the metabolism of folate. Children lence of autism,4 dentists cannot refer their

JADA, Vol. 141 http://jada.ada.org August 2010 951

Copyright © 2010 American Dental Association. All rights reserved. Reprinted by permission.
C O V E R S T O R Y

BOX 2 It may take more time to develop a positive rap-

port with these parents, but the reward of caring
Tips for understanding the for the oral health of a child with a developmental
concerns of and communicating disability is worth the effort (Box 2). Being knowl-
with parents of children who edgeable about controversial issues will help den-
have autism. tists ensure that patients with autism have the
best possible treatment outcomes. ■
dRecognize that the parents may have concerns about
environmental toxins. Disclosure. Dr. Rada did not report any disclosures.
dBe able to discuss environmental safety issues 1. Kanner L. Autistic disturbances of affective contact. Acta Pae-
regarding dental materials and offer specific references
on request. dopsychiatr 1968;35(4):100-136.
2. Steyaert JG, De la Marche W. What’s new in autism? Eur J
dDo not become upset or at odds with parents but show Pediatr 2008;167(10):1091-1101.
a willingness to listen to their concerns.
3. Rice C, Schendel D, Cunniff C, Doernberg N. Public health moni-
dKnow, or be willing to determine, whether a dental toring of developmental disabilities with a focus on the autism spec-
material is gluten free. This will show you are sensitive trum disorders. Am J Med Genet C Semin Med Genet 2004;125C(1):
to parental concerns. 22-27.
dTactfully communicate differences of opinion and 4. Kogan MD, Blumberg SJ, Schieve LA, et al. Prevalence of parent-
document, as part of the informed-consent process, reported diagnosis of autism spectrum disorder among children in the
when a parent declines a recommended treatment. US, 2007. Pediatrics 2009;124(5):1395-1403.
5. Newschaffer CJ, Croen LA, Daniels J, et al. The epidemiology of
dBe willing to offer alternative treatments. Document autism spectrum disorders. Annu Rev Public Health 2007;28:235-258.
potential limitations of alternative treatments as part
of the informed-consent process. 6. Geschwind DH. Advances in autism. Annu Rev Med 2009;60:
367-380.
dAsk whether the child is receiving any integrative or 7. Fombonne E. Epidemiology of pervasive developmental disorders.
alternative medicine interventions.
Pediatr Res 2009;65(65):591-598.
8. Herbert MR. Autism: a brain disorder or a disorder that affects the
brain? Clinical Neuropsychiatry 2005;2(6):354-379.
patients who have autism to other dentists. 9. Kinney DK, Munir KM, Crowley DJ, Miller AM. Prenatal stress
Autism is being treated with applied behavioral and risk for autism. Neurosci Biobehav Rev 2008;32(8):1519-1532.
10. Muhle R, Trentacoste SV, Rapin I. The genetics of autism. Pedi-
therapy and occupational therapy, as well as con- atrics 2004;113(5):e472-e486.
ventional, integrative and alternative medicine. 11. Goines P, Van de Water J. The immune system’s role in the
biology of autism. Curr Opin Neurol 2010;23(2):111-117.
Dentists may encounter varying and often con- 12. Pardo CA, Eberhart CG. The neurobiology of autism. Brain
flicting strategies for treatment beyond what is Pathol 2007;17(4):434-447.
13. Vargas DL, Nascimbene C, Krishnan C, Zimmerman AW, Pardo
commonly reported in the dental literature. Some CA. Neuroglial activation and neuroinflammation in the brain of
of the treatment strategies are well researched, patients with autism. Ann Neurol 2005;57(1):67-81.
14. Herbert MR, Russo JP, Yang S, et al. Autism and environmental
and others are based on a clinician’s theory that a genomics. Neurotoxicology 2006;27(5):671-684.
treatment might work, which can give some par- 15. Calderón-Garcidueñas L, Marcías-Parra M, Hoffmann HJ, et al.
Immunotoxicity and environment: immunodysregulation and systemic
ents false hope and lead them to subject their inflammation in children. Toxicol Pathol 2009;37(2):161-169.
children to costly, ineffective and potentially 16. Stewart K, Hunter Ryden L. The utilization of laboratory bio-
markers to predict and prevent neuroimmune disorders caused by envi-
unhealthy procedures. Unfortunately, treatment ronmental stressors. Autism File 2009;33:34-37.
success stories usually are based on isolated anec- 17. Autism Research Institute. Possible triggers of autism.
“http://legacy.autism.com/triggers/index.htm”. Accessed June 6, 2010.
dotal reports. It can be difficult for dentists to sort 18. Friedlander AH, Yagiela JA, Paterno VI, Mahler ME. The neu-
through this information. ropathology, medical management and dental implications of autism.
JADA 2006;137(11):1517-1527.
The facts that autism is diagnosed on the basis 19. Green D, Flanagan D. Understanding the autistic dental patient.
of behavioral characteristics and that there are no Gen Dent 2008;56(2):161-171.
20. Waldman HB, Perlman SP, Wong A. Providing dental care for the
definitive biological markers for autism are patient with autism. J Calif Dent Assoc 2008;36(17):662-670.
largely responsible for the controversies. The role 21. Ming X, Brimacombe M, Chaaban J, Zimmerman-Bier B, Wagner
GC. Autism spectrum disorders: concurrent clinical disorders. J Child
the environment plays with genetically suscep- Neurol 2008;23(1):6-13.
tible people is an area in which much of the 22. Spence SJ, Schneider MT. The role of epilepsy and epileptiform
EEGs in autism spectrum disorders. Pediatr Res 2009;65(6):599-606.
research is focused. A great deal of the progress 23. Goldberg EA. The link between gastroenterology and autism.
in managing the treatment of people who have Gastroenterology Nurs 2004;27(1):16-19.
24. Kidd PM. Autism, an extreme challenge to integrative medicine,
autism is driven by strongly proactive parent part 2: medical management. Altern Med Rev 2002;7(6):472-499.
groups.25 These parents are armed with informa- 25. Generation Rescue. Action plan. “www.generationrescue.org/
recovery/get-started”. Accessed June 6, 2010.
tion and may question standard treatment regi- 26. Roberts HW, Charlton DG. The release of mercury from amalgam
mens. The information these parents have may or restorations and its health effects: a review. Oper Dent 2009;34(5):
605-614.
may not be based in scientific fact and may seem 27. Hyman MA. Autism: is it all in the head? Altern Ther Health Med
at odds with what is considered appropriate for 2008;14(6):12-15.
28. Blaylock RL, Strunecka A. Immune-glutamatergic dysfunction as
maintaining oral health. Dental health care a central mechanism of the autism spectrum disorders. Curr Med
workers need to respond with tact and confidence. Chem 2009;16(2):151-170.

952 JADA, Vol. 141 http://jada.ada.org August 2010

Copyright © 2010 American Dental Association. All rights reserved. Reprinted by permission.
 C O V E R S T O R Y

29. Blaylock RL. A possible central mechanism in autism spectrum 45. Ibrahim SH, Voigt RG, Katusic SK, Weaver AL, Barbaresi WJ.
disorders, part 2: immunoexcitotoxicity. Altern Ther Health Med 2009; Incidence of gastrointestinal symptoms in children with autism: a pop-
15(1):60-67. ulation-based study. Pediatrics 2009;124(2):680-686.
30. James SJ, Melnyk S, Jernigan S, et al. Metabolic endophenotype 46. Buie T, Campbell DB, Fuchs GJ, et al. Evaluation, diagnosis and
and related genotypes are associated with oxidative stress in children treatment of gastrointestinal disorders in individuals with ASDs: a
with autism. Am J Med Genet B Neuropsychiatr Genet consensus report. Pediatrics 2010;(125 suppl 1):S1-S18.
2006;141B(8):947-956. 47. Elder JH. The gluten-free, casein-free diet in autism: an overview
31. Adams JB, Romdalvik J, Ramanujam VM, Legator MS. Mercury, with clinical implications. Nutr Clin Pract 2008;23(6):583-588.
lead and zinc in baby teeth of children with autism versus controls. J 48. Marcason W. What is the current status of research concerning
Toxicol Environ Health A 2007;70(12):1046-1051. use of a gluten-free, casein-free diet for children diagnosed with
32. Blaylock RL. A possible central mechanism in autism spectrum autism? J Am Diet Assoc 2009;109(3):572.
disorders, part 3: the role of excitotoxin food additives and the syner- 49. Jyonouchi H. Food allergy and autism spectrum disorders: is
gistic effects of other environmental toxins. Altern Ther Health Med there a link? Curr Allergy Asthma Rep 2009;9(3):194-201.
2009;15(2):56-60. 50. Millward C, Ferriter M, Calver SJ, Connell-Jones GG. Gluten-
33. Schuld A. Autism and G proteins. Consumer Health Organization and casein-free diets for autistic spectrum disorder. Cochrane Database
of Canada; 2000. “www.consumerhealth.org/articles/display. Syst Rev 2008;(2)2:CD003498.
cfm?ID=20001118214326”. Accessed June 5, 2010. 51. Ambrose J. Bon appetit without the wheat. Gluten-free dental
34. Levy SM, Guha-Chowdhury N. Total fluoride intake and implica- products. “www.withoutthewheat.com/Dental_Products.html”.
tions for dietary fluoride supplementation. J Public Health Dent 1999; Accessed June 6, 2010.
59(4):211-223. 52. GC America. MI Paste & MI Paste Plus frequently asked ques-
35. Bentley EM, Ellwood RP, Davies RM. Fluoride ingestion from tions. “www.mi-paste.com/faq.php#C”. Accessed June 6, 2010.
toothpaste by young children. Br Dent J 1999;186(9):460-462. 53. Horvath K, Perman JA. Autism and gastrointestinal symptoms.
36. Franzman MR, Levy SM, Warren JJ, Broffitt B. Fluoride denti- Curr Gastroenterol Rep 2002;4(3):251-258.
frice ingestion and fluorosis of the permanent incisors. JADA 2006; 54. Schultz ST, Klonoff-Cohen HS, Wingard DL, Akshoomoff NA,
137(5);645-652. Macera CA, Ji M. Acetaminophen (paracetamol) use, measles-mumps-
37. DeMattei R, Cuvo A, Maurizio S. Oral assessment of children rubella vaccination, and autistic disorder: the results of a parent
with an autism spectrum disorder. J Dent Hyg 2007;81(3):65. Epub survey. Autism 2008;12(3):293-307.
2007 July 1. 55. Alberti A, Pirrone P, Elia M, Waring RH, Romano C. Sulphation
38. Loo CY, Graham RM, Hughes CV. The caries experience and deficit in “low-functioning” autistic children: a pilot study. Biol Psychi-
behavior of dental patients with autism spectrum disorder. JADA 2008; atry 1999;46(3):420-424.
139(11):1518-1524. 56. Yagiela JA. The pediatric patient and nitrous oxide. Dimens Dent
39. Mandell DS, Morales KH, Marcus SC, Stahmer AC, Doshi J, Hyg 2008;6(7):20-22.
Polsky DE. Psychotropic medication use among Medicaid-enrolled 57. Marshall J, Sheller B, Mancl L, Williams BJ. Parental attitudes
children with autism spectrum disorders. Pediatrics 2008;121(1): regarding behavior guidance of dental patients with autism. Pediatr
e441-e448. Dent 2008;30(5):400-407.
40. Besag FM. The relationship between epilepsy and autism: a con- 58. Selzer RR, Rosenblatt DS, Laxova R, Hogan K. Adverse effect of
tinuing debate. Acta Paediatr 2009;98(4):618-620. nitrous oxide in a child with 5,10-methylenetetrahydrofolate reductase
41. Chong SK. Gastrointestinal problems in the handicapped child. deficiency. N Engl J Med 2003;349(1):45-50.
Curr Opin Pediatr 2001;13(5):441-446. 59. Nagele P, Zeugswetter B, Wiener C, et al. Influence of methyl-
42. Sullivan PB. Gastrointestinal disorders in children with neuro- enetetrahydrofolate reductase gene polymorphisms on homocysteine
developmental disabilities. Dev Disabil Res Rev 2008;14(2):128-136. concentrations after nitrous oxide anesthesia. Anesthesiology 2008;
43. Galiatsatos P, Gologan A, Lamoureaux E. Autistic enterocolitis: 109(1):36-43.
fact or fiction? Can J Gastroenterol 2009;23(2):95-98. 60. Blaylock RL. A possible central mechanism in autism spectrum
44. MacDonald TT, Domizio P. Autistic enterocolitis; is it a disorders, part 1. Altern Ther Health Med 2008;14(6):46-53.
histopathological entity? Histopathology 2007;50(3):371-379.

JADA, Vol. 141 http://jada.ada.org August 2010 953

Copyright © 2010 American Dental Association. All rights reserved. Reprinted by permission.