|Year : 2017 | Volume
| Issue : 1 | Page : 6-16
Clinical features and diagnosis of autism spectrum disorder in children
Susan Mary Zachariah, Samuel Philip Oommen, Beena Koshy
Department of Developmental Pediatrics, Developmental Paediatrics Unit, Christian Medical College and Hospital, Vellore, Tamil Nadu, India
|Date of Web Publication||17-Feb-2017|
Department of Developmental Pediatrics, Developmental Paediatrics Unit, Christian Medical College and Hospital, Vellore - 632 004, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Autism spectrum disorder (ASD) is a neurodevelopmental disorder of behavior that presents in childhood. It is a clinically heterogeneous disorder of behavior, characterized by two features - (1) impairment in social communication and interaction and (2) repetitive patterns of behavior. The diagnosis is essentially clinical and is based primarily on history-taking and observation of the child over a period. There are several standardized screening tools and scales available to help make a diagnosis. Children with autism often present with speech delay and this has to be distinguished from other conditions. ASD is often associated with comorbid conditions which have to be identified to tailor the treatment program for each child. It is important that the parents or caretakers of the child are involved in the process of assessment and diagnosis and that their misconceptions and fears are addressed.
Keywords: Autism clinical features, autism diagnosis, autism screening, autism spectrum disorder
|How to cite this article:|
Zachariah SM, Oommen SP, Koshy B. Clinical features and diagnosis of autism spectrum disorder in children. Curr Med Issues 2017;15:6-16
A 5-year-old Raju* was brought to the outpatient department by his parents who were concerned that he was not speaking appropriately for his age. His perinatal and neonatal periods were uneventful. His motor milestones were normal for age, and his parents reported that he was speaking well at around 1. year of age, which gradually decreased. He did not look at people, did not ask for anything, and preferred being alone. He was a very “independent” child. His parents found him occasionally repeating dialogs heard on television. He put everything into his mouth and mostly played by repeatedly manipulating switches and threw a tantrum when he was restrained from doing so. He liked music and advertisements on television but did not seem to respond to any other noises, including when his name was called.
- What do you think about Raju's* difficulties?
- Do you think Raju* may be deaf? How would a deaf child behave differently from how Raju* is behaving?
(Answers at the end of the discussion) *Fictional name.
| Introduction|| |
Autism spectrum disorder (ASD) is a heterogeneous disorder of behavior characterized by qualitative deficits in social communication and interaction and restricted, repetitive patterns of behavior, activities, and interests. Sensory hypersensitivities or hyposensitivities to the environment are also highly prevalent in children with ASD.
The incidence of autism is increasing worldwide. The Centers for Disease Control (CDC) estimates that the prevalence of autism in 2012 (according to The Autism and Developmental Disabilities Monitoring Network) was 14.7/1000, which translates to one in every 68 children. This is in comparison with a prevalence of 9/1000 in 2006 (23% increase) and 6.4/1000 in 2002 (78% increase) in the USA. There are limited data on the prevalence of autism in India. A population-based prevalence study done on tribal, rural, and urban areas of Himachal Pradesh showed a prevalence rate of 0.9/1000, with a higher prevalence in the rural population. There are many ongoing funded studies in India evaluating incidence and prevalence in detail. Action for autism, a national not-for-profit organization for autism in India, estimates that there are 18 million people in India with autism.
Unfortunately, the awareness among professionals and public about the disorder – when to suspect it, how to diagnose it as well as plan of intervention – is dismally poor. Hence, majority of children with autism are either misdiagnosed as mentally retarded or schizophrenic or they get diagnosed as having autism at a later age.
For an optimum outcome in children with autism, early intervention (preferably before 3 years of age) is essential. Hence, there is a critical need to improve the awareness of ASD to enable earlier detection and intervention. This article focuses on the clinical features as well as the diagnostic criteria for ASD.
| What Is Autism Spectrum Disorder?|| |
Autism is a neurodevelopmental disorder which presents in childhood and predominantly affects the behavior, language, and ability to communicate. It varies in its presentation and outcome. At one end of the spectrum are “high functioning” individuals who have normal or near-normal intelligence but with some dysfunction in communication and social interaction. On the other end are those with severe disabilities. Autistic individuals who have “savant” abilities [Box 1 [Additional file 1]] have captured media attention but represent a very small minority. The vast majority of autistic individuals have significant disabilities that impair daily living.
Autism was first described by Kanner  in 1943, who described 11 children who had two main features that were consistently noted – a profound “autistic aloofness,” preferring to be alone and aloof from everyone around, and “obsessive insistence on the preservation of sameness.” These children had extraordinary abilities, mainly in memory. He described a child named Donald as follows: “He could since the age of 2½ years, tell the names of all presidents and vice-presidents, recite the letters of the alphabet forward and backward, and flawlessly, with good enunciation, rattle off the Twenty-Third Psalm. Yet, he was unable to carry on an ordinary conversation.”
Thus, autism is characterized by difficulty in communicating with others and relating to the outside world. They have difficulties in communication (both verbal and nonverbal communication) as well as restricted, fixed interests and repetitive pa
tterns of behavior (motor, language, and play).
| What Are the Risk Factors for Autism?|| |
The etiology of autism is complex, and there seems to be both a genetic component as well as an environmental component to the same. The British twin study showed a concordance rate of 60% in monozygotic twins with autism, compared with none in dizygotic twins; and if the broader definition of social and communication disorders is considered, it increases to 92% and 100%, respectively. There are various genetic disorders known to be well associated with autism such as tuberous sclerosis, fragile X syndrome, neurofibromatosis, and Angelman syndrome. These known syndromes account for <10% of the children with autism.
The environmental causative factors can be divided into prenatal, perinatal, and postnatal factors.
These include congenital rubella syndrome, exposure to teratogens such as thalidomide  and valproic acid.
These include low birth weight, preterm delivery, and birth asphyxia.
Postnatal proposed factors
These include a wide variety of insults such as autoimmune illness, leaky gut syndrome, amygdala development failure, Vitamin D deficiency, and mercury toxicity. However, none of them have been consistently proved to be significantly associated. Autism is more common among males than females. The reason for this is not known, but many theories ranging from the extreme male brain theory due to fetal testosterone to there being a reduced autosomal penetrance in females are currently hypothesized. Vaccines were thought to cause autism, but there has been no evidence for this [Box 2 [Additional file 2]]. Increased exposure to visual media has been shown to reduce the language abilities and social interaction of children. Overexposure to electronic media in the form of television and smartphones has been considered a trigger factor for autistic symptoms [Box 3 [Additional file 3]]. It is very difficult to prove a causal relationship in this respect.
Whether the cause is due to nature or nurture or a combination of both, recent studies have shown that atypical neural connectivity in the developing brain may help to explain the difficulties in language and social communication and interaction seen in autism.,
| What Are the Clinical Features of Autism Spectrum Disorder?|| |
The clinical features that are essential in the diagnosis of autism [Figure 1] are as follows:
- Impairment in social communication and interaction
- Restrictive repetitive patterns of behavior.
Most children with autism are brought by their parents to a physician due to a delay in development of speech. Unfortunately, only a few parents note the characteristic features of autism in their children., Some of the symptoms of autism at various periods of growth and the “red flags” [Box 4 [Additional file 4]] for autism are discussed below [Table 1].,, Parents should be educated about these clinical features [Figure 2] while also addressing some of their fears and misconceptions about the condition [Box 5 [Additional file 5]].
|Figure 2: Common signs and symptoms associated with autism (©Handbook for teachers. The National Trust, a statutory body under Department for the Welfare of Persons with Disabilities (Divyangjan), Ministry of Social Justice and Empowerment, Government of India).|
Click here to view
|Table 1: Common features seen in children with autism in their 1st, 2nd and 3rd years of life|
Click here to view
| Symptoms in Infancy|| |
An infant with autism may present as early as by 6 months of age.
- They tend to be unusually quiet, prefer to be on the bed than being carried by their mother
- They may also be irritable with difficulty in feeding
- The infant may not engage in reciprocal behavior or participate in social games such as peek-a-boo
- Social smile, where the child looks at the caregiver and smiles reciprocally, may be absent or delayed
- The development may be normal till 12–18 months after which they may slow down or regress in their language and social skills.
| Symptoms in Childhood|| |
- The child may not respond to his/her name being called but is responsive to other sound stimuli
- They tend to indicate their needs by pulling the parent and placing the parent's hand on the object of desire (known as “hand-on-hand gesture”)
- Many children do not indicate any needs, becoming very independent from a young age
- They either may not speak or may have lots of self-talk or may repeat what they have heard, either immediately (immediate echolalia) or after a period (such as repeating dialogs from television, using phrases said at home nonmeaningfully – delayed echolalia)
- Many children tend to have a lot of motor stereotypies such as spinning self or objects, hand flapping, jumping, clapping, and twirling.
- They usually do not like change and get upset when their routine is disturbed
- Many of them also have unusual sensory responses – a few are hypersensitive (close ears to sounds such as the pressure cooker whistle, avoid touching sticky food, and gets upset with certain textures of clothes) and few others are hyposensitive (insensitivity to pain, preferring to walk on tip toes, looking at shadows, and mouthing all objects).
| Approach to Speech Delay|| |
Autism needs to be ruled out in any child who presents with delayed development of speech. The following flowchart is a useful approach to speech delay [Figure 3].
A clinic-based evaluation of speech delay should enquire about nonverbal communication, social interaction, and environment. Nonverbal communication including gestures and appropriate facial responses and emotions is normal in children with hearing impairment while impaired in children with autism. It is important to screen for hearing in case of even minimal suspicion. A child can have isolated speech delay where other motor skills such as walking and writing skills are unaffected; again pointing the needle of suspicion to hearing impairment. Global developmental delay where both motor and cognitive skills are impaired also can coexist with autism.
A child with speech delay can have difficulties with social communication and interaction with no stereotypes or repetitive interests, indicating a social communication disorder. Children with autism have difficulties with repetitive interests, actions, and behaviors. It is crucial to enquire about environment including electronic media exposure. Feeding and sleep concerns are common in children with autism.
| Other Conditions Presenting With Speech Delay|| |
Autism must be differentiated from developmental delay and impairment of hearing as both these conditions may present with speech delay and other symptoms similar to autism. Careful history, clinical examination, and observation of the child over time can usually help in identifying the underlying problem. This is important because the management of these conditions is very different. [Table 2] lists some of the differentiating clinical features of these clinical conditions.
| Diagnosis of Autism Spectrum Disorder|| |
Diagnosis of ASD is based on clinical history followed by observing and interacting with the child. There are no specific clinical markers or laboratory tests that can be used to diagnose autism. However, there are various standardized checklists, assessment tools, and criteria that are used to make a diagnosis of ASD.
Developmental screening of a child should be done at every visit with a health professional (particularly during immunization visits) to ensure the normal development of the child, and any parental concerns regarding communication, interaction, or behavior should be taken seriously and addressed. The flowchart in [Figure 4] is a helpful approach.
|Figure 4: Screening for autism - Flowchart depicting the approach to a child during routine immunization visits (Adapted from practice parameter: Screening and diagnosis of autism. Neurology 2000;55:468-79).|
Click here to view
Level 1 screening comprises routine developmental screening including red flags during any physician visits especially the immunization visit for babies. If there are any concerns, the Modified Checklist for Autism in Toddlers (M-CHAT) can be used as a screening tool. Any sensory impairment can be evaluated at this stage. If a child fails the screening test, the child needs to be referred to a higher center for further diagnostic purposes. It is ideal to re-screen the development at review even if the child passes the screening test.
The diagnosis of autism is based on the Diagnostic and Statistical Manual of Diseases Edition 5 (DSM-V) which has two main criteria: (1) Deficits in social communication and interaction and (2) restricted and repetitive patterns of behavior, interests, and activities [Table 3] and [Figure 5].
|Table 3: The Diagnostic and Statistical Manual of Diseases Edition 5 for autism spectrum disorder (adapted)|
Click here to view
|Figure 5: Pictorial representation of Diagnostic and Statistical Manual of Diseases Edition 5 criteria.|
Click here to view
Overview of screening and diagnostic tools
As with other conditions, screening checklists help identify children at risk of autism. Diagnostic tools are needed for a confirmatory diagnosis.
Autism Diagnostic Observational Schedule is the gold standard diagnostic tool.
- Autism Diagnostic Interview-Revised
- Childhood Autism Rating Scale
- INCLEN Diagnostic Tool for Autism (INDT-ASD): An Indian tool to diagnose autism.
The disadvantages of the diagnostic tools are that they need expert training before their administration, are expensive (except INDT-ASD which is free) and that most are based on the criteria seen in the earlier edition of DSM (DSM-IV – Text Revision) which classified ASD into five disorders.
If a child fulfills the DSM-V criteria for diagnosis of autism by history and clinical observation, a diagnosis of autism can be made under expert guidance.
| What Are the Comorbidities Associated With Autism Spectrum Disorder?|| |
The earlier term for ASD was pervasive developmental disorder, meaning that the disorder has “spillover effects” into other domains of development apart from communication and behavior.
The common comorbidities seen are as follows:
- Cognition: Around 30%–50% of children with autism have intellectual disability (intelligence quotient <70). 20%–40% of children have an average intelligence while the remaining have borderline intelligence., The pattern of intelligence may be patchy with few children having extraordinary capabilities in certain domains such as memory, mathematics, and musical abilities
- Sleep: Around 40%–80% of children with ASD have sleep problems. The common sleep problems encountered are difficulty in initiating sleep, frequent awakening, early morning awakening, and insomnia. In addition to establishing a sleep routine and providing environmental conditions conducive to sleep, some children may also require exogenous melatonin to help them sleep 
- Feeding: The estimated prevalence of feeding issues in children with autism is as high as 90%, with around 70% being “selective eaters.” Around 46% of children with ASD have rituals surrounding their eating habits 
- Epilepsy: Epilepsy commonly co-occurs with ASD. The prevalence varies from around 8% to as high as 46%. Various studies also show presence of epileptiform discharges in EEG without overt seizures, with a prevalence ranging from 20% to 60%.,, Although earlier studies showed association between epileptiform discharges and autistic regression,, further studies did not prove any correlation between them ,,
- Other psychiatric comorbidities: Around 70% of children with ASD have at least one comorbidity and around 40% have two or more.
- Anxiety is a very common comorbidity seen in children with autism, particularly around adolescence. The prevalence of anxiety is estimated to be between 11% and 84% in children with autism. Some of the most frequently reported anxiety disorders and symptoms seen in children with ASD are specific phobias (29.8%), obsessive–compulsive disorder (17.4%), social anxiety disorder (16.6%), generalized anxiety disorder, and separation anxiety disorder. Problems with anxiety are present across levels of cognitive functioning although the type of anxiety problem is likely influenced by cognitive ability
- Attention deficit hyperactivity disorder (ADHD): ADHD commonly co-occurs with ASD. Around 30%–80% of children with ASD also satisfy the criteria for ADHD and around 20%–50% of those diagnosed to have ADHD also fulfill criteria for ASD 
- Oppositional defiant disorder (ODD): In a study done by van Steensel et al., the prevalence of ODD was found to be 22.5%. Externalizing disorders such as ADHD and ODD had a higher prevalence (27.5%) than internalizing disorders (12.5%).
| Conclusion|| |
With an increasing prevalence of ASD, every doctor needs to be aware of the red flags and the clinical features of ASD to enable early identification and referral. ASD needs to be suspected in every child presenting with speech delay. Not all children with ASD have intellectual disability; some of them have remarkable talents which will help mainstream them into normal schooling. Comorbidities associated with ASD need to be looked for and addressed to improve the quality of life.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Developmental Disabilities Monitoring Network Surveillance Year Principal Investigators; Centers for Disease Control and Prevention (CDC). Prevalence of autism spectrum disorder among children aged 8 years – Autism and developmental disabilities monitoring network, 11 sites, United States, 2010. MMWR Surveill Summ 2014;63:1-21.
Raina SK, Kashyap V, Bhardwaj AK, Kumar D, Chander V. Prevalence of autism spectrum disorders among children (1-10 years of age)-findings of a mid-term report from Northwest India. J Postgrad Med 2015;61:243-6.
Kanner L. Autistic disturbances of affective contact. Acta Paedopsychiatr 1968;35:100-36.
Trottier G, Srivastava L, Walker CD. Etiology of infantile autism: A review of recent advances in genetic and neurobiological research. J Psychiatry Neurosci 1999;24:103-15.
Bailey A, Le Couteur A, Gottesman I, Bolton P, Simonoff E, Yuzda E, et al.
Autism as a strongly genetic disorder: Evidence from a British twin study. Psychol Med 1995;25:63-77.
Curatolo P, Porfirio MC, Manzi B, Seri S. Autism in tuberous sclerosis. Eur J Paediatr Neurol 2004;8:327-32.
Rogers SJ, Wehner DE, Hagerman R. The behavioral phenotype in fragile X: Symptoms of autism in very young children with fragile X syndrome, idiopathic autism, and other developmental disorders. J Dev Behav Pediatr 2001;22:409-17.
Mbarek O, Marouillat S, Martineau J, Barthélémy C, Müh JP, Andres C. Association study of the NF1 gene and autistic disorder. Am J Med Genet 1999;88:729-32.
Steffenburg S, Gillberg CL, Steffenburg U, Kyllerman M. Autism in Angelman syndrome: A population-based study. Pediatr Neurol 1996;14:131-6.
Chess S. Follow-up report on autism in congenital rubella. J Autism Child Schizophr 1977;7:69-81.
Strömland K, Nordin V, Miller M, Akerström B, Gillberg C. Autism in thalidomide embryopathy: A population study. Dev Med Child Neurol 1994;36:351-6.
Miyazaki K, Narita N, Narita M. Maternal administration of thalidomide or valproic acid causes abnormal serotonergic neurons in the offspring: Implication for pathogenesis of autism. Int J Dev Neurosci 2005;23:287-97.
Lampi KM, Lehtonen L, Tran PL, Suominen A, Lehti V, Banerjee PN, et al.
Risk of autism spectrum disorders in low birth weight and small for gestational age infants. J Pediatr 2012;161:830-6.
Gardener H, Spiegelman D, Buka SL. Perinatal and neonatal risk factors for autism: A comprehensive meta-analysis. Pediatrics 2011;128:344-55.
Torres AR, Westover JB, Rosenspire AJ. HLA immune function genes in autism. Autism Res Treat 2012;2012:959073.
Liu Z, Li N, Neu J. Tight junctions, leaky intestines, and pediatric diseases. Acta Paediatr 2005;94:386-93.
Schultz RT. Developmental deficits in social perception in autism: The role of the amygdala and fusiform face area. Int J Dev Neurosci 2005;23:125-41.
Kocovská E, Fernell E, Billstedt E, Minnis H, Gillberg C. Vitamin D and autism: Clinical review. Res Dev Disabil 2012;33:1541-50.
Thomas Curtis J, Chen Y, Buck DJ, Davis RL. Chronic inorganic mercury exposure induces sex-specific changes in central TNFa expression: Importance in autism? Neurosci Lett 2011;504:40-4.
Tuchman R. Autism. Neurol Clin 2003;21:915-32, viii.
Baron-Cohen S, Lombardo MV, Auyeung B, Ashwin E, Chakrabarti B, Knickmeyer R. Why are autism spectrum conditions more prevalent in males? PLoS Biol 2011;9:e1001081.
Greene DJ, Colich N, Iacoboni M, Zaidel E, Bookheimer SY, Dapretto M. Atypical neural networks for social orienting in autism spectrum disorders. Neuroimage 2011;56:354-62.
Lombardo MV, Chakrabarti B, Bullmore ET, Sadek SA, Pasco G, Wheelwright SJ, et al.
Atypical neural self-representation in autism. Brain 2010;133(Pt 2):611-24.
Chawarska K, Paul R, Klin A, Hannigen S, Dichtel LE, Volkmar F. Parental recognition of developmental problems in toddlers with autism spectrum disorders. J Autism Dev Disord 2007;37:62-72.
De Giacomo A, Fombonne E. Parental recognition of developmental abnormalities in autism. Eur Child Adolesc Psychiatry 1998;7:131-6.
Karande S. Autism: A review for family physicians. Indian J Med Sci 2006;60:205-15.
Nazeer A, Ghaziuddin M. Autism spectrum disorders: Clinical features and diagnosis. Pediatr Clin North Am 2012;59:19-25, ix.
Kliegman R, Stanton B, St. Geme J, Schor N, Nelson Textbook of Pediatrics. 20th
ed., Vol. 1. Canada; Elsevier; 2016. p. 176-83.
Cortesi F, Giannotti F, Ivanenko A, Johnson K. Sleep in children with autistic spectrum disorder. Sleep Med 2010;11:659-64.
Krakowiak P, Goodlin-Jones B, Hertz-Picciotto I, Croen LA, Hansen RL. Sleep problems in children with autism spectrum disorders, developmental delays, and typical development: A population-based study. J Sleep Res 2008;17:197-206.
Leu RM, Beyderman L, Botzolakis EJ, Surdyka K, Wang L, Malow BA. Relation of melatonin to sleep architecture in children with autism. J Autism Dev Disord 2011;41:427-33.
Kodak T, Piazza CC. Assessment and behavioral treatment of feeding and sleeping disorders in children with autism spectrum disorders. Child Adolesc Psychiatr Clin N
Am 2008;17:887-905, x-xi.
Twachtman-Reilly J, Amaral SC, Zebrowski PP. Addressing feeding disorders in children on the autism spectrum in school-based settings: Physiological and behavioral issues. Lang Speech Hear Serv Sch 2008;39:261-72.
Williams PG, Dalrymple N, Neal J. Eating habits of children with autism. Pediatr Nurs 2000;26:259-64.
Thomas S, Hovinga ME, Rai D, Lee BK. Brief report: Prevalence of co-occurring epilepsy and autism spectrum disorder: The U.S. National Survey of Children's Health 2011-2012. J Autism Dev Disord 2017;47, :224-9.
Spence SJ, Schneider MT. The role of epilepsy and epileptiform EEGs in autism spectrum disorders. Pediatr Res 2009;65:599-606.
Ekinci O, Arman AR, Isik U, Bez Y, Berkem M. EEG abnormalities and epilepsy in autistic spectrum disorders: Clinical and familial correlates. Epilepsy Behav 2010;17:178-82.
Parmeggiani A, Barcia G, Posar A, Raimondi E, Santucci M, Scaduto MC. Epilepsy and EEG paroxysmal abnormalities in autism spectrum disorders. Brain Dev 2010;32:783-9.
Chez MG, Chang M, Krasne V, Coughlan C, Kominsky M, Schwartz A. Frequency of epileptiform EEG abnormalities in a sequential screening of autistic patients with no known clinical epilepsy from 1996 to 2005. Epilepsy Behav 2006;8:267-71.
Oslejsková H, Dusek L, Makovská Z, Pejcochová J, Autrata R, Slapák I. Complicated relationship between autism with regression and epilepsy. Neuro Endocrinol Lett 2008;29:558-70.
Lewine JD, Andrews R, Chez M, Patil AA, Devinsky O, Smith M, et al.
Magnetoencephalographic patterns of epileptiform activity in children with regressive autism spectrum disorders. Pediatrics 1999;104(3 Pt 1):405-18.
Canitano R, Luchetti A, Zappella M. Epilepsy, electroencephalographic abnormalities, and regression in children with autism. J Child Neurol 2005;20:27-31.
Hrdlicka M, Komarek V, Propper L, Kulisek R, Zumrova A, Faladova L, et al.
Not EEG abnormalities but epilepsy is associated with autistic regression and mental functioning in childhood autism. Eur Child Adolesc Psychiatry 2004;13:209-13.
Baird G, Robinson RO, Boyd S, Charman T. Sleep electroencephalograms in young children with autism with and without regression. Dev Med Child Neurol 2006;48:604-8.
Simonoff E, Pickles A, Charman T, Chandler S, Loucas T, Baird G. Psychiatric disorders in children with autism spectrum disorders: Prevalence, comorbidity, and associated factors in a population-derived sample. J Am Acad Child Adolesc Psychiatry 2008;47:921-9.
White SW, Oswald D, Ollendick T, Scahill L. Anxiety in children and adolescents with autism spectrum disorders. Clin Psychol Rev 2009;29:216-29.
van Steensel FJ, Bögels SM, Perrin S. Anxiety disorders in children and adolescents with autistic spectrum disorders: A meta-analysis. Clin Child Fam Psychol Rev 2011;14:302-17.
Rommelse NN, Franke B, Geurts HM, Hartman CA, Buitelaar JK. Shared heritability of attention-deficit/hyperactivity disorder and autism spectrum disorder. Eur Child Adolesc Psychiatry 2010;19:281-95.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2], [Table 3]