University of Alexandria

High Institute of Public

Health

Department of Nutrition

AUTISM SPECTRUM DISORDERS

By

ORCHID ESSAM EL-DIN DARWISH

Supervisor

DR. DALIA TAYEL

1

LIST OF CONTENTS

Introduction

3

Etiology and predisposing factors

4

Clinical picture

8

Feeding problems in autism

10

Diagnosis of Autism spectrum disorders

12

Treatment options

13

References

21

2

Introduction

What Are the Autism Spectrum Disorders?

It is a lifelong complex disorder that impedes an individual’s ability to

communicate and function socially.1 Autistic spectrum disorders are set of

neurodevelopmental conditions characterized by a marked impairment in

social interaction, delayed language, and restricted patterns of behavior. In

addition to these core symptoms, autistic children frequently have serious

behavioral disturbances, such as self-injurious behavior, aggression, and

tantrums.

Usually, these behavioral problems compromise educational and

developmental progress.2 Formerly a rare condition, the prevalence of autism

has increased more than 10-fold in the past 20 years, from an estimated

prevalence of approximately5 or6 per 10,000 children to 65 per 10,000

diagnosed with ASD).1

The autism spectrum disorders are more common in the pediatric population

than are some better known disorders such as diabetes, spinal bifida, or

Down syndrome.3 A recent study of a U.S. metropolitan area estimated that

3.4 of every 1,000 children 3-10 years old had autism. 4

3

The earlier the disorder is diagnosed, the sooner the child can be helped

through treatment interventions. Pediatricians, family physicians, daycare

providers, teachers, and parents may initially dismiss signs of ASD,

optimistically thinking the child is just a little slow and will “catch up.”5

Etiology and predisposing factors:

Genetic factors:

Evidence points to genetic factors playing a prominent role in the causes for

ASD. Twin and family studies have suggested an underlying genetic

vulnerability to ASD 6 .

Recent neuroimaging studies have shown that a contributing cause for

autism may be abnormal brain development beginning in the infant’s first

months. This" growth dysregulation hypothesis” holds that the anatomical

abnormalities seen in autism are caused by genetic defects in brain growth

factors. It is possible that sudden, rapid head growth in an infant may be an

early warning signal that will lead to early diagnosis and effective biological

intervention or possible prevention of autism.7

Hypovitaminosis D and autism:

While the predisposing autistic lesion is genetic, the epidemiological

observations indicate something in the environment prenatally or

postnatally, is affecting expression of the genotype, probably through gene-

environment interactions. The environment directly influences

environmental responsive genes and they, in turn, directly influence the

genome, the neurosteroid hormones are a good example.

4

That is, while neurosteroids are under genetic organization, something in the

environment may lower neurosteroid concentrations which, in turn, fails to

signal fully the genetic expression of the neural proteins that steroid

regulates8 So it is reasonable to search for neurosteroids that have declined

over the same time autism has increased.

Of the neurosteroids involved in brain development, activated vitamin D

(calcitriol) is unique, the least understood, but, arguably, one of the most

profound. McGrath et al. alerted us to this fact in 2001, pointing out that

vitamin D is ‘‘the neglected neurosteroid’’9

In the same paper, they pointed out that calcitriol is a potent up-regulator of

nerve growth factor and that the vitamin D receptor (VDR) is found in a

wide variety of brain tissue very early in embryogenesis. They were the first

to conclude that ‘‘hypovitaminosis D should be examined in more detail as a

candidate risk factor for neurodevelopmental disorders’’

In 2006, Kalueff et al. went further, suggesting vitamin D offers

‘‘neuroprotection, antiepileptic effects, immunomodulation, possible

interplay with several brain neurotransmitter system and hormones, as well

as regulation of behaviors 10. The tissue levels of calcitriol during brain

development directly depend on maternal 25(OH)D blood levels, which, in

turn, directly depend on the amount of vitamin D the mother makes in her

skin or puts in her mouth 11.

Autistic individuals have T cell abnormalities and cytokine excesses 12that

show a striking similarity to the immune functions affected by vitamin D13.

Both the brain and the blood of autistic individuals show evidence of

ongoing chronic inflammation and oxidative stress12 , that is, the disease

5

process is probably increasingly destructive. Further hope for a nootropic

effect rests in calcitriol’s powerful anti-inflammatory properties.

Its administration down-regulates production of inflammatory cytokines in

the brain, which have consistently been associated with cognitive

impairment14 Furthermore, calcitriol is remarkably neuroprotective by

stimulating neurotropin release ,reducing toxic calcium levels in the brain,

inhibiting the production of nitrous oxide, and by its immunomodulating

properties – especially in reducing inflammatory cytokines15 and by

increasing brain glutathione.16

This last function of vitamin D, increasing cellular levels of glutathione 17,

may explain the purported link between heavy metals, oxidative stress, and

autism. For example, calcitriol attenuates iron-induced 18and zinc-induced19

oxidative injuries in rat brain. The primary route for the neurotoxicity of

most heavy metals is through depletion of glutathione and subsequent

generation of reactive oxygen and nitrogen species 20 .

Besides its function as a master antioxidant, glutathione acts as a chelating

agent to remove heavy metals, including mercury21 .A placebo controlled

three-month study of 20 autistic children found multivitamins with even low

doses of vitamin D (150 units or 3.75 mcg) significantly improved sleep and

gastrointestinal problems .22

Iron deficiency and autism

High prevalence of low serum ferritin concentration has been reported in

children with autism spectrum disorder (autism) 23 suggesting iron

6

deficiency. This condition could be expected to affect sleep, based on

research suggesting its impact on central nervous system functioning24.

Gluten and casein

It is hypothesized that some symptoms may be the result of opioid peptides

formed from the incomplete breakdown of foods containing gluten and

casein. Gluten is a casein-like substance that is found in the seeds of various

cereal plants—wheat, oat, rye, and barley. Casein is the principal protein in

milk.

Increased intestinal permeability, also referred to as the “leaky gut

syndrome,” allows these peptides to cross the intestinal membrane, enter the

bloodstream, and cross the blood-brain barrier, affecting the endogenous

opiate system and neurotransmission within the nervous system.25 The

resulting excess of opioids is thought to lead to behaviors noted in ASD, and

the removal of these substances from the diet parallels a change in autistic

behaviors.

Iodine deficiency and autism

Román 26 proposes maternal hypothyroxinemia as an important cause of

autism. . Maternal hypothyroxinemia can result from a number of different

pathways and etiologies, including iodine deficiency.

A diet deficient in iodine can result in a wide range of negative effects on the

developing fetus, from mild IQ loss to severe mental retardation, i.e.,

cretinism. 27 Additional support to the hypothesis posed by Román 26 includes

7

the decrease in the iodine nutrition status among women of childbearing age

in the U.S. over the last three decades 28

The pattern of decrease in the iodine nutrition status of a population and

concomitant increase in autism has been seen in other countries 29 Given the

marginal iodine nutrition status, exposure to antithyroid substances

including environmental pollutants such as perchlorate, organochlorines, and

tobacco smoke, these insults result in a deficit in thyroid hormones, and

when present during early pregnancy, result in hypothyroxinemia and most

likely cause autism and other neurologic sequelae.30

Clinical picture

All children with ASD demonstrate deficits in 1) social interaction, 2) verbal

and nonverbal communication, and 3) repetitive behaviors or interests31. In

addition, they will often have unusual responses to sensory experiences,

such as certain sounds or the way objects look. Each of these symptoms runs

the gamut from mild to severe. They will present in each individual child

differently.32

Children with ASD do not follow the typical patterns of child development.

In most cases, the problems in communication and social skills become

more noticeable as the child lags further behind other children the same age.

Oftentimes between 12 and 36 months old, the differences in the way they

react to people and other unusual behaviors become apparent.

Some parents report the change as being sudden, and that their children start

to reject people, act strangely, and lose language and social skills they had

previously acquired. In other cases, there is a plateau, or leveling, of

progress so that the difference between the child with autism and other

children the same age becomes more noticeable.33

8

The following possible indicators of ASD were identified on the Public

Health Training Network Webcast, Autism Among Us.34 :

Does not babble, point, or make meaningful gestures by 1 year of age

Does not speak one word by 16 months

Does not combine two words by 2 years

Does not respond to name

Loses language or social skills

Other Indicators

Poor eye contact

Doesn't seem to know how to play with toys

Is attached to one particular toy or object

Doesn't smile

At times seems to be hearing impaired

Social Symptoms

Most children with ASD seem to have tremendous difficulty learning to

engage in the give-and-take of everyday human interaction. They seem

indifferent to other people, and often seem to prefer being alone. They may

resist attention or passively accept hugs and cuddling. Children with ASD

also are slower in learning to interpret what others are thinking and feeling.

Although not universal, it is common for people with ASD also to have

difficulty regulating their emotions. This can take the form of “immature”

behavior such as crying in class or verbal outbursts that seem inappropriate

to those around them. The individual with ASD might also be disruptive and

physically aggressive at times, making social relationships still more

difficult35

9

Communication Difficulties

Some children diagnosed with ASD remain mute throughout their lives.

Some infants who later show signs of ASD coo and babble during the first

few months of life, but they soon stop. Others may be delayed, developing

language as late as age 5 to 9.

Those who do speak often use language in unusual ways. They seem unable

to combine words into meaningful sentences. Some speak only single words,

while others repeat the same phrase over and over. Another difficulty is

often the inability to understand body language, tone of voice, or “phrases of

speech.” 36

Repetitive Behaviors

Although children with ASD usually appear physically normal and have

good muscle control, odd repetitive motions may set them off from other

children. Some children and older individuals spend a lot of time repeatedly

flapping their arms or walking on their toes. Some suddenly freeze in

position.

As children, they might spend hours lining up their cars and trains in a

certain way, rather than using them for pretend play. If someone accidentally

moves one of the toys, the child may be tremendously upset. A slight change

in any routine—in mealtimes, dressing, taking a bath, going to school at a

certain time and by the same route—can be extremely disturbing. Repetitive

behavior sometimes takes the form of a persistent, intense preoccupation.

Often there is great interest in numbers, symbols, or science topics37

Feeding problems in autism

10

It should be noted that feeding problems are much more frequent than what

is observed with other children with disabilities that have some similarities

to ASD such as language impairments.38 In fact, the atypical eating styles are

so common that at one time they were considered symptomatic of ASD 39

There are a number of target areas for autistic children that are particularly

problematic compared to typical and atypically developing children.

Among these problems are:

1. Prefers food of a certain texture or smell;

2. Will eat only certain foods;

3. Eats things that are not meant to be eaten;

4. Eats too quickly; and

5. Eats too much.

The first two items could be categorized as food selectivity. These items are

generally a target for intervention due to concerns over their high frequency

in ASD.40

The latter three items could be characterized as eating style, and are

potentially very serious, even life threatening. Eating inedible items (pica)

can result in serious injury or death, through choking or intestinal blockage.

Similarly, rapid eating can be and is a life threatening behavior in some

contexts for persons with ASD.

These problems are further compounded by the fact that attempts to redirect

the child can result in greater rates of challenging behaviors. 38 Thus, early

identification of these problems, is nonetheless extremely important.

11

An approach to evaluate food problems is described by Lukens &Linscheid41

.They describe the Brief Autism Mealtime Behavior Inventory (BAMBI),

which they note to be the first standardized measure of mealtime behavior

for children with autism. The authors concluded that the BAMBI had good

internal consistency, test–retest reliability, and good construct and criterion-

related reliability.

The Diagnosis of Autism Spectrum Disorders

Although there are many concerns about labeling a young child with an

ASD, the earlier the diagnosis of ASD is made, the earlier needed

interventions can begin. Evidence over the last 15 years indicates that

intensive early intervention in optimal educational settings for at least 2

years during the preschool years results in improved outcomes in most

young children with ASD3

In evaluating a child, clinicians rely on behavioral characteristics to make a

diagnosis. For the diagnosis, problems in at least one of the areas of

communication, socialization, or restricted behavior must be present before

the age of 3. The diagnosis requires a two-stage process. The first stage

involves developmental screening during “well child” check-ups; the second

stage entails a comprehensive evaluation by a multidisciplinary team.42

Screening for ASD

A “well child” check-up should include a developmental screening test by

the pediatrician 42 Several screening instruments have been developed to

quickly gather information about a child's social and communicative

development within medical settings. Among them are the Checklist of

12

Autism in Toddlers (CHAT),43 the modified Checklist for Autism in

Toddlers (M-CHAT),44 the Screening Tool for Autism in Two-Year-Olds

(STAT),45and the Social Communication Questionnaire (SCQ)46(for children

4 years of age and older).

Screening instruments do not provide individual diagnosis but serve to

assess the need for referral for possible diagnosis of ASD.

If following the screening process or during a routine “well child” check-up,

the child's doctor sees any of the possible indicators of ASD, further

evaluation is indicated.

Comprehensive Diagnostic Evaluation

The second stage of diagnosis must be comprehensive in order to accurately

rule in or rule out an ASD or other developmental problem. This evaluation

that entails neurological and genetic assessment may be done by a

multidisciplinary team that includes a psychologist, a neurologist, a

psychiatrist, a speech therapist, or other professionals who diagnose children

with ASD.

In addition in-depth cognitive and language testing42and measures developed

specifically for diagnosing autism are often used. These include the Autism

Diagnosis Interview-Revised (ADI-R)47 and the Autism Diagnostic

Observation Schedule (ADOS-G).48The ADI-R consists of four main factors

—the child's communication, social interaction, repetitive behaviors, and

age-of-onset symptoms. The ADOS-G is an observational measure used to

“press” for socio-communicative behaviors that are often delayed, abnormal,

or absent in children with ASD.

13

Two other tests that should be used to assess any child with a developmental

delay are a formal audiologic hearing evaluation and a lead screening.

Children with an autistic disorder usually have elevated blood lead levels.42

Treatment Options

Behavioral Management

There is no single best treatment package for all children with ASD. One

point that most professionals agree on is that early intervention is important;

another is that most individuals with ASD respond well to highly structured,

specialized programs.

Among the many methods available for treatment and education of people

with autism, applied behavior analysis (ABA) has become widely accepted

as an effective treatment49. The goal of behavioral management is to

reinforce desirable behaviors and reduce undesirable ones.50 Effective

programs will teach early communication and social interaction skills. In

children younger than 3 years, appropriate interventions usually take place in

the home or a child care center.

These interventions target specific deficits in learning, language, imitation,

attention, motivation, compliance, and initiative of interaction. Included are

behavioral methods, communication, occupational and physical therapy

along with social play interventions51Children older than 3 years usually

have school-based, individualized, special education.

Dietary Intervention

Dietary interventions are based on the idea that:

Food allergies cause symptoms of autism, and

14

An insufficiency of a specific vitamin or mineral may cause some

autistic symptoms.

If parents decide to try for a given period of time a special diet, they should

be sure that the child's nutritional status is measured carefully. A diet that

some parents have found was helpful to their autistic child is a gluten-free,

casein-free diet (GFCF diet).

Since gluten and milk are found in many of the foods we eat, difficulty for

parents to follow the diet modification, the extra cost of the food, and extra

time in preparing the meals, following a gluten-free, casein-free diet is

difficult. In addition, some data suggest that children following the GFCF

diet may have increased prevalence of essential amino acid deficiencies and

bone loss 52

Some autistic children consume self-restricted diets due to sensory

limitations and may limit the number of foods to five or fewer 52. Autistic

children tend to be deficient in minerals such as sulphur, zinc, magnesium,

iodine, lithium and potassium. A supplement that some parents feel is

beneficial for an autistic child is Vitamin B6, taken with magnesium (which

makes the vitamin effective). The result of research studies is mixed; some

children respond positively, some negatively, some not at all or very little.53

The central nervous system is rich in highly unsaturated fatty acids (HUFA),

principally docosahexaenoic acid (22:6n-3, DHA) and arachidonic acid

(20:4n-6, ARA), which cannot be synthesized by the human body but must

be supplied by nutrition.

Highly unsaturated fatty acids are essential for normal brain development

and function 54 There is also increasing evidence that fatty acid deficiencies

15

or imbalances may contribute to childhood neurodevelopmental disorders,

including attention-deficit/hyperactivity disorder, dyslexia, dyspraxia, and

autistic spectrum disorders55.

Parents of children with autism who supplemented their children with

omega-3 rich fish oils reported improvements in general health, sleeping

patterns, cognitive and motor skills, concentration, eye contact, and

sociability, as well as reductions in irritability, aggression and

hyperactivity56.

The underlying mechanism of action is not understood but may be related to

modulation of serotonergic and dopaminergic neurotransmission.57

Management of feeding problems

A variety of food-related problems have been treated in ASD children such

as eating compliance, rapid eating58, inadequate food consumption, and food

packing. 59 However, food selectivity has been the most frequently studied

feeding problem60. Applied behavior analysis has been the treatment model

of choice in most instances.61

Furthermore, existing measures such as the Screening Tool of fEeding

Problems (STEP), which have been developed for persons with intellectual

disability, could be easily adapted to the ASD population 62. Functional

assessment and direct observational methods should also be included in

comprehensive assessment .63

Nutritional assessment

16

Nutrition is also a treatment modality for some autistic symptoms. With an

increasing incidence rate and proposed nutrition connections, more dietitians

will be contacted with referrals for nutritional assessment of children with

autism. The core components of autism, direct resulting behaviors expressed

in the children, and coexisting medical conditions related to autism can be

problematic to conduction of a nutritional assessment.

Dietitians must be aware of several factors when counseling a family with a

child with autism including:

o Multiple medications with serious nutritional implications,

o Serious sensory integration issues that make obtaining anthropometric

measurements difficult,

o Specialized diet patterns containing foods often not covered in standard

dietary analysis software, and

o Impaired communication skills that require reliance on parents for

information64

Medications Used in Treatment

Attempts to treat autism with medications in various chemical classes have

had limited success. Some of the better-studied medications (including

haloperidol and risperidone) often are efficacious in treating associated

symptoms of autism but also can cause unacceptable adverse effects 65 .

Medications are often used to treat behavioral problems, such as aggression,

self-injurious behavior, and severe tantrums that keep the person with ASD

from functioning more effectively at home or school. Many of these

17

medications are prescribed" off-label” This means they have not been

officially approved by the FDA for use in children and further research

needs to be done to ensure not only the efficacy but the safety of

psychotropic agents used in the treatment of children and adolescents.

A child with ASD may not respond in the same way to medications as

typically developing children. It is important that parents work with a doctor

who has experience with children with autism. The child should be

monitored closely while taking a medication.

Anxiety and depression

The selective serotonin reuptake inhibitors (SSRI's) are the medications

most often prescribed for symptoms of anxiety, depression, and/or

obsessive-compulsive disorder (OCD). Only one of the SSRI's, fluoxetine

has been approved by the FDA for both OCD and depression in children age

7 and older.

In addition, fluvoxamine (age 8 and older); sertraline (age 6 and older); and

clomipramine (age 10 and older).34Treatment with these medications can be

associated with decreased frequency of repetitive, ritualistic behavior and

improvements in eye contact and social contacts. The FDA is studying and

analyzing data to better understand how to use the SSRI's safely, effectively,

and at the lowest dose possible.

Behavioral problems

Antipsychotic medications have been used to treat severe behavioral

problems. These medications work by reducing the activity in the brain of

the neurotransmitter dopamine .Haloperidol was found in more than one

18

study to be more effective than a placebo in treating serious behavioral

problems.66However, haloperidol, while helpful for reducing symptoms of

aggression, can also have adverse side effects, such as sedation, muscle

stiffness, and abnormal movements.

Other atypical antipsychotics that have been studied recently with

encouraging results are olanzapine and ziprasidone

Seizures

Seizures are found in one in four persons with ASD, most often in those who

have low IQ or are mute. They are treated with one or more of the

anticonvulsants. These include such medications as carbamazepine

lamotrigine ,topiramate and valproic acid . The level of the medication in the

blood should be monitored carefully and adjusted so that the least amount

possible is used to be effective.

Inattention and Hyperactivity

Stimulant medications such as methylphenidate, used safely and effectively

in persons with attention deficit hyperactivity disorder, have also been

prescribed for children with autism. These medications may decrease

impulsivity and hyperactivity in some children, especially those higher

functioning children

New treatment modalities

A. Hyperbaric Oxygen Therapy (HBOT)

HBOT has produced remarkable results in supplying more oxygen-rich

blood to the cells, including the brain cells. And this has led to vast

improvements in the behavior of autistic kids. Children with autism who

received hyperbaric treatment at 1.3 atm and 24% oxygen for 40 hourly

19

sessions had significant improvements in overall functioning, receptive

language, social interaction, eye contact, and sensory/cognitive awareness

compared to children who received slightly pressurized room air.67

B. Stem cell therapy

The combined use of mesenchymal stem cells (MSC) and cord blood

CD34+cells may be useful in the treatment of autism. The treatment of

immune deregulation in autism is expected to not only cause amelioration

of intestinal and systemic symptomatology, but also to profoundly

influence neurological function 68 .

C. Secretin

The use of secretin, a substance approved by the Food and Drug

Administration (FDA) for a single dose Reports have shown

improvement in autism symptoms, including sleep patterns, eye contact,

language skills, and alertness 69.

20

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