Global Data on Autism Spectrum Disorders Prevalence: A Review of Facts, Fallacies and Limitations

Page 1

Universal Journal of Clinical Medicine 5(2): 14-23, 2017

http://www.hrpub.org

DOI: 10.13189/ujcm.2017.050202

Global Data on Autism Spectrum Disorders Prevalence:

A Review of Facts, Fallacies and Limitations

Onaolapo A Y1, Onaolapo O J2,*

1Behavioural Neuroscience/Neurobiology Unit, Department of Anatomy, Ladoke Akintola University of Technology,

Ogbomoso, Oyo State, Nigeria

2Behavioural Neuroscience/Neuropharmacology Unit, Department of Pharmacology, Ladoke Akintola University of Technology,

Osogbo, Osun State, Nigeria

the terms of the Creative Commons Attribution License 4.0 International License

Abstract Autism spectrum disorders (ASDs) are a

range of neurodevelopmental disorders whose aetiologies

are largely unknown. In the past few decades, studies have

demonstrated that ASDs occur globally, and that the

numbers of recorded cases are rising; however,

determining the true prevalence figures is still a major

challenge, especially in developing nations. Also, subtle

differences in cultural norms might impede timely/accurate

diagnosis and categorisation of patients. In this review, we

examine the globally-available data on the prevalence of

ASD and discuss some of the challenges of data acquisition,

with reference to how these may impact the reliability of

figures obtained. Some of the facts, fallacies and

limitations relating to the presently-available figures are

also highlighted.

Keywords Neurodevelopment, Aetiology, Prevalence,

Autism, Data

1. Introduction

Epidemiology is not only concerned with patterns of

disease occurrence within human populations, but it is also

concerned with the factors that determine or influence

development of disease, or maintenance of health. Over the

years, different study designs (surveillance, descriptive,

analytical, cohort, case-control and cross-sectional) have

been employed in examining the relationships that may

exist between disease and disease determinants in defined

human populations. Generally, epidemiological

investigations of neuropsychiatric diseases begin with

cross-sectional surveys, which help to determine the

prevalence of the disease condition, patterns of risk factors,

as well as the possible correlates between disease and risk

factors among representative samples [1]. The first

epidemiological survey of autism was initiated in England

in the early to mid-1960s [2, 3], while the first

hospital-based survey in sub-Saharan Africa was

conducted in five countries in the late 1970s [4]. Autism

surveys have since become global, with different countries

conducting surveys to determine the prevalence and risk

factors in their communities [1, 5], and thereby propose

strategies to improve identification, diagnosis,

management as well as promote policy reforms that bring

awareness to the plight of the autistic child.

The term ‘Autism’ derives from the Greek word "autos",

meaning "self”; and it was in the year 1911 that Eugen

Bleuler first used the word autism in describing a symptom

of schizophrenia. However, in 1943 and 1944 respectively,

Leo Kanner (USA) and Hans Asperger (Germany)

described individuals with social/emotional limitations and

withdrawn behaviours. Kanner reported behavioural

aberrations such as poor social interaction, obsessiveness,

stereotypic movement, and echolalia in the affected

children. It was Kanner who first coined the term ‘infantile

autism’ (earlier called Kanner’s syndrome) to describe his

observations in this group of children who seemed

socially-isolated and withdrawn [6]; while Asperger named

the condition he observed Asperger’s syndrome. Decades

of research will eventually reveal that both syndromes are

parts of a highly-variable spectrum of disorders. Autism

spectrum disorders (ASDs) are an array of

neurodevelopmental disorders characterised by cognitive

and neurobehavioural deficits, whose underlying factors

are genetic and/or neurobiological [7]. In the Diagnostic

and Statistical Manual (DSM) III, autism debuted in 1980

as "infantile autism", which was replaced by the term

"Autistic Disorder" in 1987. In the DSM IV, it was referred

to as pervasive developmental disorders (PDDs); and

consisted of autistic disorder (autism), Asperger disorder,

childhood disintegrative disorder, Rett syndrome, and

PDD-not otherwise specified (NOS).

Over the years, a lot has changed about our perception of

ASDs, the perceived risk factors, core diagnostic criteria,

Page 2

Universal Journal of Clinical Medicine 5(2): 14-23, 2017

and even approaches to management. Presently, according

to the DSM V, persistent deficits in social communication/

social interaction and a restricted/repetitive (stereotypical)

patterns of behaviour, interests or activities; which must be

present in the early developmental period(but might not

become obvious until social demands exceed limited

capacity), cause clinically significant impairment (in social,

occupational or other important areas of current

functioning) and must not be better explained by

intellectual disability or global developmental delay, are

the core criteria for the diagnosis of ASD [8]. DSM 5 also

makes provision for differential diagnosis such as ‘social

communication disorder’. Level of severity of symptoms

{3 levels given for both social communication/social

interaction, and restricted/repetitive (stereotypical) patterns

of behaviour} determines the degree of supportive care

needed, with level 3 severity requiring very substantial

support. Apart from the core symptoms, patients often have

co-morbid psychiatric and behavioural manifestations like

self-injury, aggression, impulsivity, hyperactivity, anxiety

and mood symptoms; all of which may worsen the overall

prognosis, stress the caregivers, and further complicate

management. Recently, results from epidemiological

surveys indicate that the global prevalence of ASDs is on

the rise; although data from sub-Saharan Africa and a

number of other developing countries still show numbers

that are generally lower than those from the developed

countries [9-11]. Whether this reflects an absolute low

prevalence, deficits in diagnostic skills, mal-adaptation of

diagnostic criteria as it relates to cultural differences in

behaviour, or under-sampling is still being studied.

The aetiology of ASD is still being studied, and despite

years of research, a complete understanding of the

causative factors is still elusive; and while it is now known

that genetics may plays a big role in ASD, a rapidly

increasing prevalence suggests a bigger role of

environmental factors.

Generally, abnormalities in neural connectivity

involving synapses, tracts and neuronal communication via

neurotransmitters are key pathological features of the brain

in autism [12]. Neurodevelopmental defects in synapse

formation/elimination and changes in ratios of

inhibitory/excitatory synapses leads to defective local and

long range connectivity [12]. An active neuroinflammatory

process involving the cerebral cortex and the cerebellum;

with associated loss of cerebellar Purkinje cells, marked

reactivity of the Bergmann’s astroglia in areas of Purkinje

cell loss, marked astroglial reactions in the granule cell

layer and cerebellar white matter, and astroglial reactions

in the middle frontal/cingulate gyri had been demonstrated

by neuropathological examinations [13].

This

neuroinflammation may have a strong link to

autoimmunity, based on demonstrable elevated levels of

immunoglobulins (IgG, IgM and IgA) against select

neuron-specific antigens in ASD children [14]; and a

significantly higher presence of serum auto-antibodies to

the human brain (notably the cerebellum and cingulate

gyrus) in autistic children) [15].

The cause(s) of the above-mentioned pathological

changes are traceable to both genetics and the environment.

The heterogeneity of ASD is not only reflected in its

behavioural manifestations, but also in the genetic basis, as

many candidate ASD genes have been studied or

implicated [16]. Also, while studies may differ in terms of

their conclusions regarding the degree of involvement of

genetics, it is generally accepted that genetics plays a

crucial role in ASD. Presently, candidate genes that have

been implicated in ASD include those that encode for

neural adhesion molecules, ion channels, scaffold proteins,

protein kinases, receptor/carrier proteins, signaling

modulator molecules, and circadian relevant proteins [17].

Environmental factors that had been linked to

ASD-associated neuroinflammation and immune

dysfunction include early-life exposure to various

xenobiotics including heavy metals such as lead, mercury

and aluminium [18]. The Ethyl mercury compound

(Thimerosal) is a bacteriostatic agent that was a component

of a number of childhood vaccines in Western nations. The

possibility of its involvement in ASD led to its removal

from many vaccines meant for children; and while it must

be noted that this was not accompanied by a sharp decline

in ASD prevalence, its continued use in vaccines given to

pregnant women further complicates the picture [18]. The

use of aluminium(Al) as an adjuvant in many vaccines has

continued, due to the fact that Al salts help to stimulate the

immune system to yield adequate antibody titres [19].

However, there is abundant scientific literature on the

neurotoxic effects of Al; and its ability to adversely affect

both the immune and the nervous systems, hence making it

a plausible risk factor for triggering ASD [18]. Al’s ability

to alter neuronal gene expression can also affect the

response of neurons to environmental insults such as toxins

[18]. The presence and abundance of environmental risk

factors may be a major determinant of geographical

variations in the true prevalence figures of ASD; however,

the wide variety of candidate environmental risk factors

makes matching environmental factors to prevalence a

challenging task.

There have also been reports suggesting that some of the

behavioural characteristics of “autistic” children in

developing countries differ, when compared to those in

developed nations [20, 21]. Along this line, how

prevalence figures are influenced by the beliefs and

cultural heritages of the different regions of the world is a

matter of debate. In this review, we discuss the global

epidemiology of ASDs by highlighting the incontrovertible

facts relating to its prevalence, fallacies of

misinterpretation of available figures as they are, and

limitations of data acquisition, diagnosis and categorisation

of patients. We also summarise how these factors impact

strategies to improve identification, diagnosis and

management; as well as promote policy reforms.

Page 3

Global Data on Autism Spectrum Disorders Prevalence: A Review of Facts, Fallacies and Limitations

1.1. Global Prevalence of ASDs

1.1.1. Prevalence in USA, Europe, China, Japan, Middle

East, Ecuador, Brazil and Mexico

Global data on the prevalence of disorders that now fall

under the term ASDs had been available before 2013. In a

2012 review that compared prevalence data from different

parts of the world (excluding sub-Saharan Africa), the

researchers estimated the median global prevalence of

17/10,000 (approx. 1 in 588) for autistic disorder, and

62/10,000 (approx. 1 in 161) for all pervasive

developmental disorders; while suggesting that the

increase in estimates over time and the variability between

countries and regions may be linked to diagnostic

switching, the broadening diagnostic criteria, service

availability and the increasing global autism awareness

[22]. Even prior to this, the epidemiology of ASDs had

portrayed a shifting dynamics, with prevalence increasing

from 2-4/10,000 children as reported in the 1940s [23], to

approximately 4-5/10,000 children, according to the

studies that were published in the 1960s and 1970s [24, 25],

11/1000 children in the USA, according to a survey

conducted about a decade ago [26]; while a Centres for

Disease Control and Prevention surveillance report

revealed a combined estimated prevalence of 14.6 per

1,000, or 1 in 68 children (aged 8 years, whose parents or

guardians resided in 11 ADDM Network sites) in the

United States [27]. The most recent CDC figures on ASD

published in 2015 (which are believed to be more accurate)

say 1 in 45 children in the USA have ASD; this is however

based on a parent survey which was designed to track the

prevalence of developmental disorders in children aged 3

to 17 years [28]. Studies in Europe recorded before 1999

reported prevalence rates ranging from 1.9 to 72.6 per

10,000 with a median of 18.75/10,000; while studies

conducted after 1999 reported rates ranging from 30.0/10

000 to 116.1/10 000, with a median rate of 61.9/10 000 [22].

In the United Kingdom, a 2006 study in 9-10 year-olds

reported a prevalence of childhood autism as 38.9/10,000,

while other ASDs (DSM III) was 77.2/10,000 (52.1-102.3),

making the total prevalence of all ASDs 116.1/10,000 [29].

However, in 2014, the National Autistic Society reported

that 1 out of every 100 children has ASD [30]. In China, it

was estimated that 1.1 in every 1,000 children are

diagnosed with autism [31]; while in an analysis of five

studies from mainland China, an estimated pooled mean

prevalence of 24.4 per 10,000 children was observed [32].

In a 2012 review of epidemiological studies conducted in

the Western Pacific region (including Japan and China)

since 2000, Elsabbagh et al. [22] reported that prevalence

rates varied from 2.8/10 000 to 94/10 000 with a median

value of 11.6/10 000. In the Middle East, the prevalence of

ASD was reported to be 1.4/10,000 in Oman, 29/10,000 in

the United Arab Emirates, and 4.3/10,000 in Bahrain

[33-37].

In Canada, the National Epidemiological Database for

the Study of Autism in Canada (NEDSAC) ranks ASD as

one of the most common developmental disabilities,

affecting 1 in 94 children [38]. A pilot study that was

conducted in Brazil reported a prevalence rate of 27/10,000

[39]; while the prevalence of ASD in regular

schoolchildren in Quito, Ecuador was found to be

11/10,000 persons [40]. The Leon survey in Mexico

reported an overall prevalence of 87/10, 000; a rate that

was deemed consistent with other studies conducted at a

similar period [41].

1.1.2. Prevalence of Autism in Sub-Saharan Africa, India

and the Caribbean Islands

According to the World Health Organisation, the global

prevalence of ASD has been estimated as 1 per 160 persons

[42]. However, the contribution of sub-Saharan Africa

(SSA) to this burden is largely unknown due to a paucity of

population-based surveys on autism in this region [10, 11,

22, 42, 43]. Data (largely from hospital-based studies) are

however available from a few countries in the region. In

south-west Nigeria, Lagunju et al [44] reported a

prevalence rate of 2.3% (1 in 43.5) amongst 2,320

first-time attendees of a neurology or child psychiatry

clinic. In another clinic-based study in south-eastern

Nigeria, prevalence of ASD was reported to be 0.8% (1 in

125) of the total number of children attending the clinic for

that year [45]; while in Uganda, a survey of 1,169 children

aged between 2 and 9 years reported an unadjusted

prevalence for ASD of 6.8/1000 [46]. All studies reported a

male predilection, and middle to high socioeconomic status

improved the likelihood of a child being evaluated for ASD.

While these studies provided some data, the absence of

data from large scale epidemiological studies from a

number of countries in this region have been suggested as a

possible reason for the perceived low incidence and/or

prevalence of autism observed in SSA [10, 11].

Until recently, India (like SSA) had a paucity of

community-based population studies for autism; although

there was a number of hospital-based autism clinical

assessment studies [47-49]. However, in a 2017

population-based study (of 28, 078 children aged between

1 and 10 years, cutting across geographical regions that

represent rural, urban, and tribal populations in India) using

the Hindi version of the Indian Scale for Assessment of

Autism; a prevalence of 0.15% (1 in 667) was reported,

with a male sex predilection [50]. Also, a high

socioeconomic status increased the likelihood of an ASD

diagnosis [50]. The prevalence of ASD in the study was

observed to be higher amongst children aged between 4

and 10 years with majority of them diagnosed with mild

autism; while amongst children aged between 1 and 7 years,

the diagnosis of moderate autism was prevalent. This was

however attributed to families delaying presentations till

the onset of delayed motor and speech development [50].

In an earlier study, the same authors (sampling 11,000

children within the same age range, and from the same

Page 4

Universal Journal of Clinical Medicine 5(2): 14-23, 2017

region) reported a prevalence of 0.0009 % (1 in 1100), with

low socioeconomic status correlating positively with

autism [51].

In the Caribbean islands, the Aruba Autism Project

determined the prevalence of ASDs in birth years

1990–1999 in Aruba, and found a figure of 53/10,000 [52].

2. Autism Spectrum Disorders: The

Facts and Fallacies

Autism fact sheets from different advocacy groups

(Autism Society, National Autism Association, National

Autism Network, Talk About Curing Autism, National

Autism Network, Autism South Africa, Action In Autism,

Autism Speaks etc.) irrespective of region or country

generally accept and reiterate that autism is a

bio-neurological developmental disability which generally

appears before the age of 3; impacting normal brain

development in the areas of social interaction,

communication skills, and cognitive function. There have

also been suggestions that autism is a disease of developed

countries, with a male sex predilection, that does not affect

life expectancy. While currently, there is yet no cure for

autism, early diagnosis and treatment helps to improve the

diverse symptoms associated with autism.

2.1. ASDs Occur Globally

In relation to the prevalence of ASDs, data emanating

from developed nations appear more comprehensive and

reliable, compared to those from developing nations.

Despite this, one fact that can no longer be denied is that as

it stands today, ASDs occur globally irrespective of culture,

geography or degree of industrialisation; with variable

degrees of tangible data from different regions of the world

where studies had been conducted. Hence, contrary to what

might have been believed in the past, especially in the

developing countries, it is not a disorder of ‘the West’ or of

advanced nations. The realisation of this fact is of

particular importance in SSA and other regions of the

world where awareness levels are still growing.

2.2. ASD Prevalence Figures are Still Rising

Globally, the recorded prevalence figures for ASDs are

rising; and from a statistical point of view, this is

undeniable when we examine data from both developed

and developing countries. However, in many developing

countries, the reported rates continue to be significantly

lower than the developed countries [9]. Whether this truly

reflects an absolute low prevalence, deficits in diagnostic

skills, mal-adaptation of diagnostic criteria as it relates to

cultural differences in behaviour, or under sampling are

issues that continue to be discussed. The idea that the low

prevalence rates observed in SSA could be due to

underreporting stemmed from studies conducted amongst

children born to African immigrants in Sweden [53-55],

that reported high prevalence rates in this subset of the

population, compared to the indigenous population. The

possibility of late diagnosis or misdiagnosis has also been

considered, and studies have shown that African children

are more likely (than Caucasian children) to have a late

diagnosis of ASD [56], or a misdiagnosis [57].

Despite the lower figures (when compared to developed

nations), it is safe to say that even in SSA, the prevalence

rates of ASDs are on the rise; and there has been an

‘improvement’ from an era of no prevalence figures [22] to

the availability of hospital-based [44], or

community–based [46] prevalence figures. Also, in India,

the prevalence from a 2017 study [38] revealed a rise from

an earlier 2015 study [51].

In developed nations, a number of researchers have

attributed the rise in ASD prevalence to an increasing

ability to diagnose, or a possible reflection of the success of

public health systems in better-identifying children who

were previously undiagnosed [58]; and this is also related

to the continued redefinition of diagnostic criteria [22]. An

increased awareness is also thought to be largely

responsible for changing figures in less developed regions

of the world, such as SSA [10, 11], and Asia [50, 51].

Comparing the two Indian studies cited earlier [50, 51], it is

obvious that more children were recruited in the 2017 study

than were in the 2015; suggesting that in the 2 year period,

more families were aware enough to want to seek diagnosis

and treatment for their wards. There is also evidence of

increasing awareness, cultural reorientation and the

availability of well-trained child and adolescent care

specialists and allied professionals in SSA. In the last

decade, particularly in the last 5 years, the number of ASD

related studies in this region [44, 46, 59-61] has increased

considerably, compared to the preceding decades.

A review of a recent CDC data published in the National

Health Statistics Reports [28] also supports the theory that

changes in awareness, earlier diagnosis, and redefinition of

diagnostic criteria has a lot of impact on prevalence figures.

While the autism rate appeared to rise 79 % over a 3-year

period, the rate of developmental delay dropped 36 % [28];

and the combined prevalence of children diagnosed with

autism, developmental delay and intellectual disability did

not change over the 3 years. The unchanging statistic of the

sum data suggests that a number of children who were once

tagged as having developmental delay or intellectual

disability are now being identified as having autism [28].

In a study involving Danish children, Hansen and

colleagues [62] were also of the opinion that the increase in

prevalence of ASD was actually due to changes in how the

disease is diagnosed [62]. By using data from a large study

involving 677, 915 Danish children (born between 1980

and 1991) and tracked until they either had an autism

diagnosis or reached the terminal date of the study (Dec. 31,

2011); the authors concluded that significantly more

Page 5

Global Data on Autism Spectrum Disorders Prevalence: A Review of Facts, Fallacies and Limitations

children were diagnosed with autism in 1995 and thereafter,

than before 1994 (when autism became a spectrum of

disorders in Denmark) [62]. However, the authors also

noted what appears to be a certain degree of real increase in

prevalence.

Several researchers also share the opinion that there is a

real global rise in prevalence of ASDs, and the rise may be

the product of several factors such as exposure to

environmental toxins and increasing parental age/genetic

susceptibility [63-65]. Immune dysregulation in pregnancy

has also been linked to the rising prevalence of ASD; and

autoimmune inflammatory disorders, such as coeliac

disease and rheumatoid arthritis in mothers are believed to

increase the risk [66]. Inflammation due to common

infections and endemic parasitic illnesses are probably not

likely associated with increased risk; and this is consistent

with the observation that in some developing nations such

as Nigeria or Cambodia, where parasitic and infectious

diseases are still common, recorded ASD prevalence is still

low [45, 67].

The continued increase in prevalence figures of ASDs in

developed countries led to the postulation of the “Biome

Depletion Theory” by some researchers, who believe that

maternal immune response overreaction is a factor

underlying the development of ASDs in offsprings.

According to this theory, our immune system has

co-evolved alongside microbes and parasites, but a lack of

these pathogens in urban, post-industrial societies leads to

immune system over reactivity [67]. Along this line, it was

suggested that pro-biotics may be able to control the

inflammatory response in pregnant women, and prevent

some cases of ASD; however, this notion still seems like a

shot in the dark, and studies will have to be conducted to

examine this.

The apparent induced immune system over-reactivity

also formed the basis of an implied link between

vaccination and ASDs. In 1998, a case series published by

Wakefield and colleagues, but later retracted by 10 of the

12 authors suggested that the measles, mumps, and rubella

(MMR) vaccine could predispose to behavioural symptoms

that are representative of ASDs in children. Despite certain

obvious shortcomings of this study {including the very

small sample size (n=12)}; the publication generated a

social firestorm that led to some parents rejecting

vaccination for their children. However, epidemiological

studies conducted thereafter failed to establish such a link

[68, 69]. The CDC also continues to reiterate its position

that no such links exist. Again, a number of developing

countries who have contributed to the global data on ASD

prevalence do not have immunisation regimens like MMR;

and even if they do, data establishing a link appear

non-existent. From the foregoing, the following are

apparent: a) an undeniable deduction from the study by

Hansen et al [62]is that is not all new cases of ASDs are

explicable by changes in diagnostic ability; hence, it might

be unscientific and over simplistic to attribute all to

improved ability to diagnosis b) The public response that

followed the Wakefield article attests to the societal and

social burden of ASDs, and the dangers of the inability of

science to find a sound and timely answer in relation to the

cause(s) of a disorder that continues to plague more

children. It is therefore imperative to continue to research

and identify environmental and social factors that may

increase risk of ASDs.

2.3. ASD has a Male Sex Predilection

Sexual predilections in disease prevalence are

well-recognised, and female predilections have been

reported consistently in a number of disorders with

autoimmune aetiologies [70] while a male preponderance

has been observed in some neurodevelopmental disorders

[71-73] ASDs have also been observed to have a higher

prevalence in males, compared to age-matched females; in

a 4:1 ratio. This observation has been consistent across

populations, regions and time; strongly suggesting the

involvement of sex-specific biological factors in ASD

aetiology [74, 75]. Genetic studies have demonstrated that

females are protected from the effects of de novo and

heritable ASD risk variants, with suggestions that sex

hormones or sex chromosomal genes may modulate these

genetic variations [74], for a detailed review on the

influence of sex in autism (see Halladay et al., [75]).

2.4. ASD and Life-expectancy

It is generally believed that autism per se does not affect

life expectancy; however, research continues to show

higher mortality risk among individuals with ASD. In

comparison with mortality statistics from the general

population or general population controls, the risk of

premature mortality has been estimated to be 2-fold to

10-fold higher in the ASD population; even autistic adults

without a learning disability are 9 times more likely than

controls, to die by suicide [76]. Also, risk of mortality is

higher in females, compared to males [77]. Accidents such

as drowning and co-morbid medical conditions such as

epilepsy are among the classic causes of death; however,

these cannot fully account for the life span gap between

autistic and non-autistic people, or the difference in

mortality between autistic people with and without an

intellectual disability [76]. One of the factors that could

account for this gap is an increase in the prevalence of

health problems such as diabetes and respiratory disease;

and the fact that these health problems may go unnoticed

until it is too late [76]. Among autistic adults, pressures of

meeting the obligations of ‘normal life’ may lead to

continued isolation, depression and suicide. The

relationship between ASD and life-expectancy deserves

further studies, especially, with the realisation that certain

life-threatening medical conditions are more common in

ASD patients. Therefore, it might be erroneous to simply

Page 6

Universal Journal of Clinical Medicine 5(2): 14-23, 2017

state that ASD does not affect life-expectancy without

explaining the ever-increasing complexity of the

relationship.

3. ASD Global Epidemiology:

Limitations of Acquisition,

Interpretation and Viability of Data

An accurate global comparison of data relating to the

prevalence of ASDs is a rather challenging task, due to

factors such as; a) the absence of data from large scale

epidemiological studies from a number of countries,

especially in the sub-Saharan countries like Nigeria (where

most of the available rates emanated from hospital-based

studies); even, developed nations like the USA cannot

boast of a truly all-inclusive national survey, probably due

to impediments of cost effectiveness and logistics b) the

information gathering tools are not totally adaptable to or

may not yield 100 % accuracy in some regions of the world

because of certain cultural peculiarities that might affect

diagnosis or categorisation c) there could be wide regional

variations in figures arising from the same country, as is the

case with China [32].

3.1. Absence of Population-based Prevalence Data in

Developing Countries

The prevalence figures of ASD in sub-Saharan Africa

have been based mainly on a few hospital-based studies,

and hardly any community-based study, except that of

Kakooza-Mwesige et al [46] in Uganda. Under these

circumstances, under-sampling or ‘skewed’ sampling have

been suggested to negatively impact the reported

prevalence [10, 11]. The study by Lagunju et al [44] was

conducted in a tertiary hospital setting in south-west

Nigeria, while that of Bakare et al [45] was conducted in a

similar setting in south-eastern Nigeria. These centres are

the ultimate referral centres for paediatric patients in their

respective regions and they represent a ‘gathering point’

for all ‘puzzling’ and ‘unusual’ childhood illnesses. First, it

must be noted that there are other regions (in the country),

for which there are no data. Secondly, confidently drawing

an inference from such studies is associated with two

potential pitfalls; that of under-representation, due to an

apparent small sample size, compared to the total

population of children within the age range; or of

over-representation, because the sampling frame is

compelled to fall on an area where such cases are likely to

cluster. This clustering effect may the apparent from the

figures; in Nigeria, Lagunju et al [44] sampled from the

paediatric neurology clinic and got a prevalence of 23/1000

and Bakare et al [45] sampled from a general paediatric

clinic to return a figure of 8/1000; while in Uganda,

Kakooza-Mwesige et al [46] sampled from the community

and got an unadjusted figure of 6.8/1000. It is obvious that

the true figures are likely to be gotten from the community,

and the present figures should be treated with caution until

larger community-based studies are carried out. However,

while the value of an epidemiological study for assessment

of needs and priorities within a community cannot be over-

emphasised; the cost implication of such studies may be

high, with a number of developing countries not finding

them easily-affordable, especially in the face of pressures

from other competing priorities.

3.2. Impact of Culture

Cultural differences play a large role in disease diagnosis,

especially when considering the diagnosis of disorders that

tends to attract a lot of social stigma; therefore, despite

adequate sensitisation and awareness, parents may still

refuse to submit their children for ASD evaluation. For

instance, in South Korea, a risk of intense stigmatisation

makes many families of children with developmental

delays to intentionally avoid diagnosis of ASD; also

cultures that believe that speech development in the male

child is usually slower than females make seeking early

help for the child to be impossible [9]. Therefore, societal

or parental behaviours affect ASD prevalence figures.

The lack of a culturally-adaptable tool for ASD

screening constitutes another impediment to having

reliable prevalence data; since culture/language differences

might affect diagnosis rates. Different cultures have

peculiar behaviours that are at least acceptable, if not even

desirable. Diagnosis of ASD is not based on laboratory

tests, but rather, on the exhibition of certain behaviours.

These behaviours include the tendency to establish eye

contact, ability to form relationships with others,

milestones in language development, and the presence of

certain repetitive motor and play behaviours. Cultural

perceptions affect the exhibition of at least some of these

behaviours; and in different cultures, parental perceptions

of their presence or otherwise affect the timing of seeking

help for a child with possible ASD. Therefore, behaviours

that are considered normal in some cultures may fall within

the inclusion criteria for ASD diagnosis.

Generally, in Europe and America, children are expected

and encouraged to make eye contact with others; but in

other parts of the world such as Asia and Africa, or even

among native communities in America and Europe, this is

not encouraged, and may even be perceived as rudeness or

insubordination, especially, when interacting with adults.

This has made certain researchers to be of the opinion that

the matter of use of eye contact as a diagnostic criterion for

autism needs to be handled with caution. There are also

cultural variations in the degree of a child’s interaction

with others, especially with adults. There are cultures all

over the world (Africa, Asia, Central and South America)

that don’t encourage ‘undue’ interactions between children

and adults (especially strangers). How children in these

cultures form relationships may not be exactly what is

Page 7

Global Data on Autism Spectrum Disorders Prevalence: A Review of Facts, Fallacies and Limitations

taken to be normal in urban Europe or America; and ASD

diagnosis in these communities may face an uphill task

when the children encounter these ‘strangers’(healthcare

personnel) that are questioning, examining and observing

them. Along this line also, language development may be

difficult to assess with all certainty, as the child may simply

be scared or ‘ashamed’ to talk to an unfamiliar adult;

leading to a situation where the parents vouch that the child

could speak, but he/she will refuse to communicate during

the assessment.

Since cultural differences may impair diagnosis of ASDs,

it is imperative to develop universally-adaptable diagnostic

criteria that are applicable to all cultures. In order to

achieve this, studies must be conducted across cultures to

find common markers that consistently differentiate

children with ASD from typically-developing children.

These markers are to be inserted as probes when gathering

data from communities. This gives an opportunity to

conduct a thorough and truly-comparable epidemiological

research, which gives rise to more reliable figures. Until

this has been achieved, it might be erroneous to simply

assume that the same criteria can be applied across

different cultures, without the need for culture-based

adjustments.

4. Conclusions

While a lot of progress had been made in the global

awareness of ASD, much remains to be done in order to

have a more accurate picture of the trend or global burden

of the disorder; and as science strives to understand more

about it, our minds need to be continuously open to do

away with certain erroneous or inaccurate impressions.

However, reaching an accurate diagnosis, accessing

therapy, acquiring epidemiological data and determining

true prevalence figures are still major challenges,

especially in developing nations. Also, research needs to

focus on dealing with cultural and social

norms/peculiarities that may hinder early diagnosis and

application of appropriate interventions. Continuous

development and application of culture-friendly and yet

globally-comparable diagnostic tools will go a long way in

bridging the gap in the ability to diagnose ASD that exists

between developing and developed nations. Finally, large

scale epidemiological studies will help towards obtaining a

truer picture of the prevalence of ASD in developing

countries, especially in sub-Saharan Africa.

Compliance with Ethical Standards

This article does not contain any studies with human

participants or animals performed by any of the authors.

Conflict of Interest

Onaolapo AY declares that she has no conflict of interest.

Onaolapo OJ also declares that he has no conflict of

interest.

Acknowledgements

This research did not receive any specific grant from

agencies in the public, commercial, or not-for-profit

sectors.

REFERENCES

[1] Fombonne E (1999) The epidemiology of autism: A review.

Psychological Medicine. 29, 769-86

[2] Lotter V (1966) Epidemiology of autistic conditions in

young children: I. Prevalence. Social Psychiatry 1, 124–137.

[3] Lotter V (1967) Epidemiology of autistic conditions in

young children: II. Some characteristics of the parents and

children. Social Psychiatry 1, 163–173.

[4] Lotter V (1978) Childhood autism in Africa. Journal of

Child Psychology and Psychiatry. 19(3), 231 – 244.

[5] Hill AP, Zuckerman K., Fombonne E (2015) Chapter 2

Epidemiology of autism spectrum disorders. In M. d. l. A.

Robinson-Agramonte (ed.) Translational Approaches to

Autism Spectrum Disorder, DOI

10.1007/978-3-319-16321-5_2

[6] Kanner L (1943) Autistic disturbances of affective contact.

Nervous Child 2, 217-50.

[7] Kim SK. (2015) Recent update of autism spectrum disorders

Korean Journal of Pediatrics. 58, 8-14

[8] APA, American Psychiatric Association. (2013) Diagnostic

and statistical manual of mental disorders. 5th ed.

Washington, DC. pp. 50–59.

[9] Maguire C (2013) Autism on the Rise: A Global Perspective.

Harvard College, Global health Review. 4 (1)

[10] Abubakar A, Ssewanyana D, Newton CR (2016) A

Systematic review of research on autism spectrum disorders

in sub-Saharan Africa. Behavioural Neurology. 3501910,

http://dx.doi.org/10.1155/2016/3501910

[11] Franz L, Chambers N, von Isenburg M, de Vries PJ (2017)

Autism spectrum disorder in sub-Saharan Africa: A

comprehensive scoping review. Autism Research.

10,723-749. doi: 10.1002/aur.1766.

[12] Belmonte MK, Allen G, Beckel-Mitchener A, Boulanger

LM, Carper RA, Webb SJ. (2004) Autism and abnormal

development of brain connectivity. J Neurosci. 24,

9228-9231.

[13] Vargas DL, Nascimbene C, Krishnan C, Zimmerman AW,

Pardo CA (2005) Neuroglial activation and

Page 8

Universal Journal of Clinical Medicine 5(2): 14-23, 2017

neuroinflammation in the brain of patients with autism. Ann

Neurol. 57, 67-81.

[14] Vojdani A, Campbell AW, Anyanwu E, Kashanian A, Bock

K, Vojdani E (2002) Antibodies to neuron-specific antigens

in children with autism: possible cross-reaction with

encephalitogenic proteins from milk, Chlamydia

pneumoniae and Streptococcus group A. J Neuroimmunol.

129, 168-177.

[15] Singer HS, Morris CM, Williams PN, Yoon DY, Hong JJ,

Zimmerman AW (2006) Antibrain antibodies in children

with autism and their unaffected siblings. J Neuroimmunol.

178, 149-155.

[16] Bacchelli E, Maestrini E (2006) Autism spectrum disorders:

molecular genetic advances. Am J Med Genet C Semin Med

Genet. 142C, 13-23.

[17] Yang ZL, Sun GL (2016) Research advances in candidate

genes for autism spectrum disorder. Zhongguo Dang Dai Er

Ke Za Zhi. 18, 282-7.

[18] Shaw CA, Sheth S, Li D, Tomljenovic L (2014) Etiology of

autism spectrum disorders: Genes, environment, or both?

OA Autism. 2, 11

[19] Brewer JM (2006) (How) do aluminium adjuvants work?

Immunol Lett. 102, 10-15.

[20] Lotter V (1980) Cross cultural perspectives on childhood

autism. Journal of Tropical Pediatrics 26, 131 -133

[21] Bakare MO, Munir KM (2011) AutismSpectrum Disorders

in Africa, A Comprehensive Book on Autism Spectrum

Disorders, Dr. Mohammad-Reza Mohammadi (Ed.), ISBN:

978-953-307-494-8, InTechOpen.

[22] Elsabbagh, M., Divan, G., Koh, Y.J., Kim, Y.S., Kauchali, S.,

Marcin, C., et al. (2012) Global prevalence of autism and

other pervasive developmental disorders. Autism Research.

5, 160-179.

[23] Wing, L., Potter, D. (2002) The epidemiology of autistic

spectrum disorders: is the prevalence rising? Mental

retardation and developmental disabilities research

reviews.8, 151-61.

[24] Gillberg, C., Wing, L. (1999) Autism: not an extremely rare

disorder. Acta Psychiatrica Scandinavica. 99, 399–406

[25] Fombonne, E. (2005) Epidemiology of autistic disorder and

other pervasive developmental disorders. Journal of Clinical

Psychiatry.36:272–281.

[26] Kogan, M.D., Blumberg, S.J., Schieve, L.A., Boyle, C.A.,

Perrin, J.M., Ghandour, R.M., et al. (2007) Prevalence of

parent-reported diagnosis of autism spectrum disorder

among children in the US, 2007. Pediatrics 124, 1395-403.

[27] Centres for Disease Control and Prevention. Prevalence of

autism spectrum disorder among children aged 8 years –

autism and developmental disabilities monitoring network,

11 sites, United States, 2010. MMWR Surveill Summ 2012;

61:1–19

[28] Zablotsky, B., Black, L.I., Maenner, M.J., Schieve, L.A.,

Blumberg, S.J. (2015) Estimated Prevalence of Autism and

Other Developmental Disabilities Following Questionnaire

Changes in the 2014 National Health Interview Survey.

National Health Statistics Report. 13(87), 1-20.

[29] Baird G, Simonoff E, Pickles A, Chandler S, Loucas T,

Meldrum D, Charman T (2006) Prevalence of disorders of

the autism spectrum in a population cohort of children in

South Thames: the Special Needs and Autism Project

(SNAP). Lancet. 368(9531), 210-5.

[30] The National Autistic Society (2014) What is Autism?

www.autism.org.uk/about-autism.

[31] Saraceno B, Saxena S (2002) Mental health resources in the

world: results from Project Atlas of the WHO,” World

Psychiatry 1, 40-44.

[32] Cubells JF (2013) Prevalence of autism spectrum disorders

in China. Shanghai Archives of Psychiatry. 25, 176–177.

[33] Al-Ansari, A.M., Ahmed, M.M. (2013) Epidemiology of

autistic disorder in Bahrain: prevalence and obstetric and

familial characteristics. Mediterrenean Health Journal. 19,

769-774.

[34] Al-Farsi, Y.M., Al-Sharbati, M.M., Al-Farsi, O.A.,

Al-Shafaee, M.S., Brooks, D.R., Waly, MI. (2011) Brief

report: Prevalence of autistic spectrum disorders in the

Sultanate of Oman. Journal of Autism Developmental

Disorders. 41, 821-825.

[35] Al-Salehi, S.M., Al-Hifthy, E.H., Ghaziuddin, M. (2009)

Autism in Saudi Arabia: presentation, clinical correlates and

comorbidity. Transcultural Psychiatry. 46, 340-347.

[36] Eapen, V., Mabrouk, A.A., Zoubeidi, T., Yunis, F. (2007)

Prevalence of pervasive developmental disorders in

preschool children in the UAE. Journal of Tropical

Pediatrics. 53, 202-205.

[37] Salhia, H.O., Al-Nasser, L.A., Taher, L.S., Al-Khathaami,

A.M., El-Metwally, A.A. (2014) Systemic review of the

epidemiology of autism in Arab Gulf countries.

Neurosciences (Riyadh). 19(4), 291-6.

[38] Ouellette-Kuntz H, Coo H, Yu CT, Lewis ME, Dewey D,

Hennessey PE, Jackman PD, Breitenbach MM, Holden JJ

(2012) Status report - National Epidemiologic Database for

the Study of Autism in Canada (NEDSAC). National

Epidemiological Database for the Study of Autism in

Canada NEDSAC; www.nedsac.ca Chronic Dis Inj Can. 32,

84-9.

[39] Paula CS, Ribeiro SH, Fombonne E, Mercadante MT. (2011)

Brief Report: Prevalence of Pervasive Developmental

Disorder in Brazil: A Pilot Study. Journal of Autism

Developmental Disorders. 41, 1738–1742. doi:

10.1007/s10803-011-1200-6.

[40] Dekkers LMS, Groot NA, Mosquera END, Z��iga IPA,

Delfos MF (2015) Prevalence of Autism Spectrum

Disorders in Ecuador: A Pilot Study in Quito J Autism Dev

Disord. 45(12): 4165–4173.

doi:10.1007/s10803-015-2559-6

[41] Fombonne E, Marcin C, Manero AC, Bruno R, Diaz C,

Villalobos M, Ramsay K, Nealy B (2016), Prevalence of

Autism Spectrum Disorders in Guanajuato, Mexico: The

Leon survey J Autism Dev Disord Volume 46, 1669–1685.

[42] WHO, World Health Organisation. (2013) Autism Spectrum

Disorders & Other Developmental Disorders. From Raising

Awareness to Building Capacity. Geneva, Switzerland.

Page 9

Global Data on Autism Spectrum Disorders Prevalence: A Review of Facts, Fallacies and Limitations

[43] Newton CR, Chugani DC (2013) The continuing role of

ICNA in Africa: how to tackle autism? Developmental

Medicine and Child Neurology. 55, 488–489.

[44] Lagunju IA, Bella-Awusah TT, Omigbodun OO (2014)

Autistic disorder in Nigeria: profile and challenges to

management. Epilepsy Behav. 39:126-9.

[45] Bakare MO, Igwe MN, Odinka PC, Iteke O (2011)

Neuropsychiatric diagnosis and psychotropic medication

prescription patterns in a mental hospital-based child and

adolescent psychiatric service in Nigeria. Journal of Health

Care for the Poor and Underserved. 22, 751-5.

[46] Kakooza-Mwesige A, Ssebyala K, Karamagi C, Kiguli S,

Smith K, Anderson MC, et al. (2014) Adaptation of the "ten

questions" to screen for autism and other

neurodevelopmental disorders in Uganda. Autism.

18,447-57.

[47] Kalra V, Seth R, Sapra S (2005) Autism --experiences in a

tertiary care hospital. Indian Journal of Pediatrics. 72,

227-30.

[48] Divan G, Vajaratkar V. Desai MU, Strik-Lievers L, Patel V

(2012) Challenges, coping strategies, and unmet needs of

families with a child with autism spectrum disorder in Goa,

India. Autism Research. 5, 190-200.

[49] Malhi P, Singhi PA (2014) A retrospective study of toddlers

with autism spectrum disorder: Clinical and developmental

profile Annals of the Indian Academy of Neurology. 17,

25-9.

[50] Raina SK, Chander V, Bhardwaj AK, Kumar D, Sharma S,

Kashyap V, et al (2017) Prevalence of Autism Spectrum

Disorder among Rural, Urban, and Tribal Children (1-10

Years of Age). Journal of Neuroscience in Rural Practice. 8,

368-374.

[51] Raina SK, Kashyap V, Bhardwaj AK, Kumar D, Chander V

(2015) Prevalence of autism spectrum disorders among

children (1-10 years of age) - findings of a mid-term report

from Northwest India. Journal of Postgraduate Medicine 61,

243-6.

[52] van Balkom IDC, Bresnahan M, Vogtl�nder MF, van

Hoeken D, Minderaa RB, Susser E, Hoek HW (2009)

Prevalence of treated autism spectrum disorders in ArubaJ

Neurodev Disord. 1, 197–204.

doi:10.1007/s11689-009-9011-1

[53] Gillberg C, Schaumann H, Gillberg IC (1995) Autism in

immigrants: children born in Sweden to mothers born in

Uganda. Journal of Intellectual Disability Research. 39, 141

– 144.

[54] Gillberg IC, Gillberg C (1996) Autism in immigrants: a

population-based study from Swedish rural and urban areas.

Journal of Intellectual Disability Research. 40, 24 – 31.

[55] Barnevick-Olsson M, Gillberg C, Fernell E (2008)

Prevalence of au tism in children born to Somali parents

living in Sweden: a brief report. Developmental Medicine

and Child Neurology.50, 598 – 601.

[56] Mandell DS, Ittenbach RF, Levy SE, Pinto-Martin JA (2007)

Disparities in diagnoses received prior to a diagnosis of

autism spectrum disorder. Journal of Autism and

Developmental Disorders. 37, 1795-802.

[57] Bello-Mojeed MA, Ogun OC, Omigbodun OO, Adewuya

OA (2010) Late identification of autistic disorder in Nigeria:

an illustration with 2 case reports. Nigerian Journal of

Psychiatry 9, 31–35.

[58] Nevison CD (2014) A comparison of temporal trends in

United States autism prevalence to trends in suspected

environmental factors. Environmental Health 13, 73. doi:

10.1186/1476-069X-13-73.

[59] Sharma JR, Arieff Z, Gameeldien H, Davids M, Kaur M,

Van Der Merwe L (2013) Association analysis of two

single-nucleotide polymorphisms of the RELN gene with

autism in the South African population. Genetic Testing and

Molecular Biomarkers. 17, 93–98.

[60] Schlebusch L, Samuels AE, Dada S 92016) South African

families raising children with autism spectrum disorders:

relationship between family routines, cognitive appraisal

and family quality of life. Journal of Intellectual Disability

Research. 60, 412–423.

[61] Bello-Mojeed MA, Omigbodun OO, Bakare MO, Adewuya

AO (2017) Pattern of impairments and late diagnosis of

autism spectrum disorder among a sub-Saharan African

clinical population of children in Nigeria. Global Mental

Health (Cambridge). 21, 4:e5.

[62] Hansen SN, Schendel DE, Parner ET (2015) Explaining the

increase in the prevalence of autism spectrum disorders the

proportion attributable to changes in reporting practices

JAMA Pediatrics 169,56-62.

[63] Hallmayer J, Cleveland S, Torres A, Phillips J, Cohen B,

Torigoe T, et al (2011) Genetic heritability and shared

environmental factors among twin pairs with autism.

Archives of General Psychiatry. 68:1095–1102.

[64] Dufault R, Lukiw WJ, Crider R, Schnoll R, Wallinga D,

Deth R (2012) A macroepigenetic approach to identify

factors responsible for the autism epidemic in the United

States.

Clinical

Epigenetics.

doi:

10.1186/1868-7083-4-6.

[65] Grabrucker AM (2013) Environmental factors in autism.

Frontiers in Psychiatry. 4, 1–13.

[66] Velasquez-Manoff M (2015) An Immune Disorder at the

Root of Autism,” The New York Times,

http://www.nytimes.com/2012/08/26/opinion/

[67] Parker W (2013) “Helminthic Therapy: Reconstituting the

depleted biome to prevent immune disorders,” The

Environmental Illness Resource,

http://www.ei-resource.org/articles/candida-and-gut-dysbio

sis-articles/.

[68] Taylor B, Miller E, Farrington CP, Petropoulos MC,

Favot-Mayaud I, Li J, et al (1999) Autism and measles,

mumps, and rubella vaccine: No epidemiologic evidence for

a causal association. Lancet. 353, 2026–9.

[69] Dales L, Hammer SJ, Smith NJ (2001) Time trends in autism

and in MMR immunization coverage in California. Journal

of the American Medical Association. 285, 1183–5.

[70] Whitacre CC (2001) Sex differences in autoimmune disease.

Nature Immunology. 2(9), 777-80.

[71] Barbaresi WJ, Katusic SK, Colligan RC, Pankratz VS,

Weaver AL, Weber KJ, et al (2002) How common is

Page 10

Universal Journal of Clinical Medicine 5(2): 14-23, 2017

attention-deficit/hyperactivity disorder? Incidence in a

population-based birth cohort in Rochester, Minnesota.

Archives of Pediatric and Adolescent Medicine. 156, 217-24

[72] Viding E, Spinath FM, Price TS, Bishop DV, Dale PS,

Plomin R (2004) Genetic and environmental influence on

language impairment in 4-year-old same-sex and

opposite-sex twins. Journal of Child Psychology and

Psychiatry. 45, 315-25.

[73] Pinborough-Zimmerman J, Satterfield R, Miller J, Bilder D,

Hossain S, McMahon W (2007) Communication disorders:

prevalence and comorbid intellectual disability, autism, and

emotional/behavioral disorders. American Journal of Speech

and Language Pathology. 16, 359-67.

[74] Werling DM, Geschwind DH (2013) Sex differences in

autism spectrum disorders Current Opinion in Neurology. 26,

146–153.

[75] Halladay, A.K., Bishop, S., Constantino, J.N., Daniels, A.M.,

Koenig, K., Palmer, K., et al. (2015) Sex and gender

differences in autism spectrum disorder: summarizing

evidence gaps and identifying emerging areas of priority.

Molecular Autism 6, 36. doi: 10.1186/s13229-015-0019-y

[76] Hirvikoski T, Mittendorfer-Rutz E, Boman M., Larsson, H.,

Lichtenstein, P., Bolte, S. (2016) Premature mortality in

autism spectrum disorder The British Journal of Psychiatry

208, 232–238. doi: 10.1192/bjp.bp.114.160192.

[77] Mouridsen SE, Bronnum-Hansen H, Rich B, Isager T (2008)

Mortality and causes of death in autism spectrum disorders:

an update. Autism 12, 403–14.