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International Journal of Biological Sciences logoLink to International Journal of Biological Sciences
. 2018 May 12;14(7):717–725. doi: 10.7150/ijbs.24063

The prevalence of autism spectrum disorders in China: a comprehensive meta-analysis

Fei Wang 1,2,#, Li Lu 1,#, Shi-Bin Wang 2,#, Ling Zhang 3,#, Chee H Ng 4, Gabor S Ungvari 5, Xiao-Lan Cao 6, Jian-Ping Lu 6, Cai-Lan Hou 2, Fu-Jun Jia 2,✉, Yu-Tao Xiang 1,✉
PMCID: PMC6001678  PMID: 29910682

Abstract

There are conflicting prevalence estimates of autism spectrum disorders (ASDs) in mainland China (China thereafter). This study is a comprehensive meta-analysis of the pooled prevalence of ASDs in the general population in China. Study investigators independently conducted a systematic literature search of the following databases: PubMed, EMBASE, PsycINFO, China National Knowledge Infrastructure, Chinese biomedical literature service system, and Wan Fang. Studies reporting prevalence of ASDs and autism in Chinese population were identified and analysed using the Comprehensive Meta-Analysis program with the random effects model. Forty-four studies were included in the meta-analysis comprising 2,337,321 subjects of whom 46.66 % were females. The mean age of subjects ranged from 1.6 to 8 years. Based on diagnostic criteria the pooled prevalence of ASDs was 39.23 per 10,000 (95% CI: 28.44-50.03 per 10,000, I2=89.2%); specifically, the prevalence of autism was 10.18 per 10,000 (95% CI: 8.46-11.89 per 10,000, I2=92.5%). Subgroup analyses revealed significant difference in the prevalence of ASDs between genders (72.77 per 10,000 in males vs. 16.45 per 10,000 in females). In conclusion, the prevalence of ASDs and autism in China was found generally lower than those reported in other countries. Further studies are needed to clarify the variation in prevalence.

Keywords: Autism spectrum disorder, prevalence, meta-analysis, China

Introduction

Autism spectrum disorders (ASDs) refer to a group of pervasive developmental disorders caused by a combination of genetic and environmental factors. They are often associated with pronounced personal suffering and heavy burden of care to families and society 1. ASDs consist of several subtypes, with autism being the core and the most common one. ASDs usually occur in infancy 2 and present with complex symptoms. Children with ASDs usually have difficulties in understanding language and social behaviors; parental concern is often centered around their children presenting abnormal behaviors, such as mutism, echolalia and lack of expressive emotion 3.

Accurate estimation of the prevalence of ASDs is important for the health sectors to understand its impact on the general population and provide appropriate resource allocations. A number of epidemiological studies have found an increasing trend in prevalence of ASDs, for example, in the 1990s the prevalence rate of ASDs were 4-5 per 10,000 in the USA, as compared to 113 per 10,000 in 2008 4. The apparent growing trend could be partly explained by the discrepancy in age of subjects, diagnostic criteria and sampling methods 5. In addition, there is wide variation in the prevalence of ASDs between countries. For instance, the prevalence of autism was 34 per 10,000 in USA 6 versus 99 per 10,000 in the UK 7. A review of 23 studies found that the estimated prevalence of ASDs across Asia countries/ territories (China, Japan, Israel, Iran, Taiwan and Indonesia) varied from 1.1 to 21.8 per 10,000 8.

In China, prevalence studies of ASDs have shown conflicting findings. Moreover, most studies were published in Chinese-language journals that are not accessible to international readership. A review of 24 studies 9 found that the pooled prevalence of ASDs in Chinese children was 24.5 per 10,000. Another meta-analysis of 18 studies in China 10 found that a pooled prevalence of autism of 11.8 per 10,000. More than 20 ASDs prevalence studies have been recently published in Chinese, which have enhanced the epidemiological dataset, but are generally not accessible to the international readership. Therefore, we set out to conduct this comprehensive meta-analysis of the pooled prevalence of ASDs in China and also to examine its mediating factors (e.g., gender, region, study period, and diagnostic tools used).

Methods

Search strategy and selection criteria

The literature search process is shown in Figure 1. Two investigators (WF and LL) independently searched the literature using PubMed, EMBASE, PsycINFO, China National Knowledge Infrastructure, Chinese biomedical literature service system (SinoMed) and Wan Fang, from their inception to February 1st 2017. Search terms included ('autism' or 'autistic disorder' or 'autism spectrum conditions' or 'pervasive developmental disorders' or 'Asperger') and ('epidemiology' or 'cross-sectional study' or 'prevalence' or 'rate') and ('China' or 'Chinese'). In order to avoid missing any studies, the reference lists of relevant review or meta-analyses were searched manually. If more than one publication was reported based on the same dataset, only the paper with complete data was included.

Figure 1.

Figure 1

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Flow chart of the study

Inclusion criteria were as follows: 1) cross-sectional or cohort studies conducted in mainland China (China thereafter) (only baseline data were extracted in the latter); 2) participants aged ≤18 years; 3) the diagnosis of ASD was established by either clinical diagnostic criteria [such as the Diagnostic and Statistical Manual of Mental Disorder (DSM), Chinese Classification of Mental Disorder (CCMD) or International Classification of Disease (ICD) systems], or screening tools [such as the Clancy Autism Behavior Scale (CABS), Children Autism Spectrum Test (CAST) and Checklist for Autism in Toddlers (CHAT)]. Both clinical diagnostic criteria and screening tools on ASDs and autism were involved because they have been widely used in epidemiology and clinical practice in China.

Studies selection and data extraction

After removing the duplicates, two investigators (WF and LL) independently screened the titles and abstracts of all records, and then selected the articles that fulfilled the inclusion criteria. Any uncertainties were resolved by consensus or with a third reviewer (WSB).

The same two investigators independently performed the data extraction using a standard data extraction form. Information extracted included the study characteristics (e.g., title, the first author, publication year, study site, survey time, sample method, sample size, response rate), ASD subtype, age, gender proportion, residence (urban/ rural area), screening and diagnostic tools, and data on the prevalence of ASDs and subtypes.

Quality assessment

Two investigators (WF and LL) independently assessed the quality of included studies using a methodological quality assessment tool with 8 items 11, 12. Each study was scored from 0 to 8. The score of 7-8 indicated 'high quality', 4-6 indicated 'moderated quality' and 0-3 indicated 'low quality' 12. Any disagreement in the assessment process was discussed and resolved with a third investigator (WSB).

Statistical analysis

The Comprehensive Meta-Analysis software version 2 was used to synthesize the data. Due to the heterogeneity in sampling methods, assessment instruments and sample size across studies, random-effects model was used to estimate the pooled prevalence of ASD 13. The I2 statistic was used to assess the degree of heterogeneity across included studies. Sensitivity and subgroup analysis were used to examine the sources of heterogeneity if present. Publication bias was evaluated with the funnel plots and Egger's test and the significance level was set at 0.05 (two-sided).

Results

Search results and characteristics of studies

Of 2,375 eligible papers identified in literature search, 44 fulfilled the inclusion criteria after screening the titles, abstracts and full texts, and removing the duplicates (Figure 1). Five of these studies were published in English and thirty-nine in Chinese. Their sample size ranged from 259 to 1,348,030 subjects and 42 studies had a sample size greater than 1000. The 44 included studies had a total of 2,337,321 subjects of which 46.66% were females. Sixteen studies reported on the prevalence of ASDs, while 28 focused on the prevalence of autism.

The characteristics of the included studies are shown in Table 1. These studies were conducted between 2000 and 2016 in 30 provinces/ municipalities/ autonomous regions in China. Mean age of the subjects ranged from 1.6 to 8 years, with the median age of 4 years. Twenty-seven studies were conducted in urban areas (61.4%) and the others were in both urban and rural areas (urban/rural were defined by the studies included in the meta-analysis). Twenty-seven studies were conducted in eastern China, nine in central China, seven studies in western China, and one study was a national survey. The CABS was the most commonly used screening tool (22/44).

Table 1.

Characteristic of the included studies

Study
year		 First Author Ref Region Sample
Size		 Area*
(urban/ rural)		 Age (years) Sample Sampling
methods		 Screening/ diagnostic tools Diagnostic
criteria		 Autism events according to diagnostic criteria ASD events according to diagnostic criteria
1996 Luo 30 Fujian 10802 Mixed 0 to 14 G CL ABC CCMD-2-R; DSM 3 3 ——
1999 Jiang 31 Luoyang 10140 Mixed NA to NA PS,K R —— DSM 3 3 ——
2000 Ren 32 Tongling 3559 Urban 3 to 5 K CL CABS —— —— ——
2001 Zhang 33 Guiyang 4999 Urban 0 to 6 G S; CL CABS; CARS CCMD 5 ——
2001 Guo 34 Tianjin 5000 Urban 0 to 6 G R CABS; CARS; PEP CCMD 5 ——
2001 Wang 35 Changzhou 7344 Mixed NA to NA G S; CL CABS CCMD 9 ——
2003 Yang 36 Zunyi 10412 Urban NA to NA PS R ABC DSM 4 6 ——
2003 Liu 37 Beijing 21866 Mixed 2 to 6 G S; CL CABS; CARS DSM 4 14 ——
2003 Guo 38 Dingxi 3770 Mixed 2 to 6 G R CABS; CARS DSM 4 3 ——
2004 Zhang 39 Tianjin 7345 Urban 2 to 6 G R CABS DSM 4 8 ——
2006 Ji 40 Nationwide 585679 Both 2 to 17 G R Disability screening questionnaire ICD10 124 ——
2007 Su 41 Tianjin 7904 Urban 1.5 to 3 REG S; CL CHAT; CARS DSM 4 22 ——
2007 Zhang 42 Wuxi 25521 Urban 1 to 6 C CL CHAT;CABS; CARS DSM 4 25 ——
2008 Wang 43 Meizhou 4156 Urban 2 to 6 K CL CABS —— —— ——
2009 Pu 44 Guizhou 3211 Urban 2 to 6 K CL CABS DSM 4 7 ——
2009 Huang 45 Tianjin 8000 Urban 1.5 to 3 G M CHAT DSM 4 —— 22
2009 Zhou 46 Shenzhen 2960 Urban 1 to 2 G R CHAT —— 9 ——
2009 Wu 47 Lianyungang 8532 Urban 0 to 3 C R CHAT; CARS DSM 4 9 ——
2009 Chen 48 Daqing 7034 Mixed 2 to 6 K, G S; CL CABS; ABC DSM4 —— 17
2009 Liang 49 Maoming 2485 Urban 3 to 6 K CL CABS ICD10; DSM 4 35 ——
2009 Liu 50 Shanghai 259 Urban 1.5 to 2 K CL CHAT DSM 4 1 2
2009 Wang 51 Guizhou 6111 Urban 2 to 6 K M CABS; CARS DSM 4 —— 46
2009 Yu 52 Haerbin 7059 Mixed 2 to 6 K S; CL CABS;ABC DSM 4 15 16
2009 Li 53 Tianjin 8274 Urban 1.5 to 3 REG S; CL CHAT; CARS DSM4 22 ——
2011 Li 54 Guiyang 1550 Urban 1.5 to 3 C CL M-CHAT; ABC DSM 4 48 ——
2011 Wei 55 Shenzhen 3624 Urban 1.5 to 2 C CL CHAT; CARS DSM4 7 10
2012 Wang 56 Lianyungang 2090 Both 1.5 to 3 C S; CL CABS DSM-V —— 24
2012 Li 57 Changchun 9714 Urban 0 to 6 G R ABC; CARS CCMD3 15 ——
2012 Chen 58 Zhuhai 4754 Both 1.5 to 3 REG R CHAT; CARS DSM4 —— 14
2012 Yang 59 Wuhan 8695 Urban 3 to 7 K CL CABS —— —— ——
2012 Duan 60 Zhengzhou 1000 NA 1.5 to 3 C CL CHAT; CARS; ABC DSM 4 —— 9
2012 Wu 61 Ningxia 1348030 NA 0 to 14 REG CL ABC; CARS ICD-10 419 ——
2013 Li 62 Shenzhen 1845 Urban 1.5 to 2 C CL CABS DSM-IV 4 ——
2013 Wang 63 Shantou 51968 Urban 3 to 6 REG R CABS ICD 10 139 ——
2013 Gao 64 Zhongshan 12804 Both 3 to 6 K S; CL CABS —— —— ——
2013 Deng 65 Hengyang 7041 Both 2 to 6 K CL CABS; CARS DSM 4 16 42
2014 Wang 66 Jiangmen 65651 Both 2 to 7 K CL CABS; ABC ABC 97 ——
2014 Wang 67 Zaozhuang 6634 NA 2 to 6 K S; CL CABS DSM-5 —— 44
2014 Yang 68 Shenzhen 15188 Urban 3.83 to 4.83 K CL ABC —— —— ——
2014 Jiang 69 Shanghai 9665 Urban 4 to 6 K CL CABS;ASSQ ADI-R;DSM-5 9 9
2014 Sun 70 Beijing 701 Urban 6 to 11 PS CL CAST ADOS;ADIR —— ——
2014 Lu 71 Shanghai 5704 Urban 2 to 6 K CL CABS DSM-5 —— 6
2014 Cheng 72 Ningbo 12123 Both 1 to 6 C S; CL CHAT; ABC DSM-IV-TR —— 14
2015 Tian 73 Jilin 6118 Urban 6 to 11 PS CL CAST CCMD —— 39
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* Rural/urban areas were defined by included studies. Sample screen: C, clinical service; G, general population; K, kindergarten; PS, population sample; REG, registration data; Sample method: CL, cluster; M, multiphase; R, random; S, stratified Screen tools: ABC, Autism Behavior Checklist; CABS, Clancy Autism Behavior Scale; CARS, Childhood Autism Rating Scale; CHAT, Checklist for Autism in Toddlers; M-CHAT, Modified Checklist for Autism in Toddlers; CAST, Children Autism Spectrum Test; ASSQ, high function Autism Spectrum screening questionnaire; PEP, Childhood Autism And Developmental Disabilities Psychological Assessment Scale (Psycho-educational Profile, PEP); Diagnostic criteria: ADI-R, Autism Diagnostic Interview-Revised; CCMD-2-R, Chinese Classification of Mental Disorders, 2nd edition, revised; DSM-III-R, Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised; DSM-IV, Diagnostic and Statistical Manual of Mental Disorders, 4th edition; DSM-V, Diagnostic and Statistical Manual of Mental Disorders, 5th edition; ICD-10, International Classification of Diseases, 10th revision; ASC, autism spectrum conditions;

Evaluation quality of the studies

The quality assessment scores ranged from 4 to 8. Based on the assessment criteria, 7 studies were rated as 'high quality', and 37 was as 'moderate quality' (Table 4).

Table 4.

Quality assessment of the included studies

Items Yes, n (%) No, n (%) Unclear, n (%)
1. Is the target population clearly defined? 43 (97.7) 1 (2.27) 0
2. Was either of the following ascertainment methods used [must be one or the other]? (1) probability sampling, or (2) entire population surveyed 41 (93.2) 3 (6.82) 0
3. Is the response rate >70% 26 (59.1) 18 (40.9) 0
4. Are nonresponders clearly described? 2 (4.5) 42 (95.5) 0
5. Is the sample representative of the target population? 42 (95.5) 2 (4.5) 0
6. Were data collection methods standardized? 44 (100) 0 0
7. Were validated criteria used to assess for the presence/absence of disease? 44 (100) 0 0
8. Are the estimates of prevalence given with confidence intervals and in detail by subgroup (if applicable)? 9 (20.5) 35 (79.5) 0
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Prevalence of ASDs

Prevalence of ASDs based on clinical diagnostic criteria

The pooled prevalence of ASDs from 16 studies with available data was 39.23 per 10,000 (95% CI: 28.44 to 50.03 per 10,000, I2=89.2%) (Figure 2A). The prevalence of ASDs in males (72.77 per 10,000) was higher than in females (16.45 per 10,000). The prevalence of ASDs in rural areas was higher than in urban areas (62.26 per 10,000 vs. 32.73 per 10,000). The pooled prevalence of ASDs from studies conducted in or before 2012 was slightly higher than that those after 2012 (38.72 per 10,000 vs. 36.36 per 10,000) after study years were dichotomized using median splitting method. The prevalence of ASDs in eastern and central China was 45.81 per 10,000 and 50.85 per 10,000, respectively. Meta-regression analysis did not find any association between age and prevalence of ASDs (p=0.784). Subgroup analyses of diagnostic instruments used revealed no difference between prevalence of ASDs established by CCMD (63.75 per 10,000), DSM-4 (41.87 per 10,000) or DSM-5 (48.96 per 10,000). However, one prevalence study using the Autism Diagnostic Observation Schedule (ADOS) (85.59 per 10,000) showed a higher figure than others (Table 2).

Figure 2.

Figure 2

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A) Forest plot of prevalence of autism spectrum disorders based on clinical diagnostic criteria. B) Forest plot of prevalence of autism based on clinical diagnostic criteria

Table 2.

Subgroup analyses of prevalence of ASD and autism based on clinical diagnostic criteria

Number of studies N Event I2 (%) P Prevalence
(per 10000)		 95% CI (per 10000)
Lower 		95% CI (per 10000)
Upper		 u-value P
ASDs 16 87917 320 89.29 <0.001 39.23 28.44 50.03 1457.90
Gender Male 13 41155 253 98.77 <0.001 72.77 54.16 91.39 30.343 <0.001
Female 13 36137 50 93.98 <0.001 16.45 11.85 21.06
Area Urban 6 35744 88 91.27 <0.001 32.73 20.52 44.95 0.216 0.642
Rural 2 8384 26 96.5 <0.001 62.26 37.29 161.80
Study time 2009-2012 9 44882 178 98.55 <0.001 38.72 26.49 50.94 0.689 0.406
>2012 7 43035 136 99.24 <0.001 36.36 19.75 52.98
Study site East of China 11 59665 191 99.16 <0.001 45.81 34.05 57.58 0.392 0.531
West of China --- --- --- --- --- --- --- ---
Central China 5 28252 123 98.51 <0.001 50.85 31.69 70.02
Diagnostic criteria ADOS 1 701 6 - - 85.59 64.88 106.30 1.924 0.588
CCMD 1 6118 39 - - 63.75 57.63 69.87
DSM-4 10 57005 192 98.74 <0.001 41.87 30.26 53.47
DSM-5 4 24093 83 99.52 <0.001 48.96 24.99 72.93
Autism 25 2218950 987 99.975 <0.001 10.18 8.46 11.89 97232.57
Gender Male 14 423777 360 99.69 <0.001 20.50 12.98 28.02 8.679 0.003
Female 14 370495 119 98.80 <0.001 6.12 3.08 9.16
Area Urban 20 304580 434 96.36 <0.001 14.80 9.87 19.72 4.105 0.043
Rural 5 506027 147 95.45 <0.001 6.06 1.13 11.00
Study time 1996-2008 8 657661 199 99.60 <0.001 8.18 4.36 12.00 5.113 0.024
2009-2013 8 85530 200 94.05 <0.001 20.40 14.05 26.74
Study site East of China 14 227497 401 99.38 <0.001 14.62 9.86 19.38 0.556 0.757
West of China 6 1371972 488 99.94 <0.001 6.41 2.41 10.40
Central China 2 19854 18 98.55 <0.001 8.68 3.51 20.87
Diagnostic criteria ABC 1 65651 97 - - 14.78 13.85 15.70 4.149 0.386
CCMD 5 37859 37 94.77 <0.001 10.05 4.52 15.57
DSM-III 1 10140 3 - - 2.96 1.90 4.02
DSM-IV 13 108131 150 97.33 <0.001 17.03 13.09 20.97
ICD-10 4 1994209 691 99.95 <0.001 10.14 8.10 12.19
Age (years) ≤2.08 5 15552 82 96.92 <0.001 40 10 140 0.976 0.323
>2.08 4 40208 128 8.861 <0.001 20 10 70
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Diagnosis tools: ABC, Autism Behavior Checklist; ADOS: Autism Diagnostic Observation Schedule; CCMD, Chinese Classification of Mental Disorders; DSM-III, Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised; DSM-IV, Diagnostic and Statistical Manual of Mental Disorders, 4th edition; DSM-V, Diagnostic and Statistical Manual of Mental Disorders, 5th edition; ICD-10, International Classification of Diseases, 10th revision

Prevalence of ASDs based on screening tools

The pooled prevalence of ASDs from 11 studies with available data was 429.07 per 10,000 (95% CI: 324.45 to 533.69 per 10,000, I2=99.5%) (Figure 3A). The prevalence of ASDs in males (503.53 per 10,000) was slightly higher than in females (294.22 per 10,000). Prevalence of ASDs in rural and urban was 50.03 per 10,000 and 141.74 per 10,000, respectively. Median splitting method was used to dichotomize continuous variables in subgroup analysis. Prevalence of ASDs from studies conducted in and before 2012 was 1149.51 per 10,000, while those done after 2012 was 188.30 per 10000. The prevalence of ASDs in eastern China (494.32 per 10,000) was higher than central China (290.11 per 10,000), while no data was available in western China. Age was collapsed into two groups (≤4 years; >4 years) using median splitting method. The prevalence of ASDs in children aged ≤4 years were higher than in children > 4 years (530 per 10,000 vs. 80 per 10,000). Eleven studies using the CABS, CAST, and CHAT, respectively provided different screening rates (422.06 per 10,000 vs. 499.29 per 10,000 vs. 431.86 per 10,000) (Table 3).

Figure 3.

Figure 3

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A) Forest plot of prevalence of autism spectrum disorders based on screening tools B) Forest plot of prevalence of autism based on screening tools

Table 3.

Subgroup analyses of prevalence of ASD and autism based on screening tools

Number of studies N Event I2(%) P Prevalence
(per 10000)		 95% CI
(per 10000); Lower		 95% CI
(per 10000); Upper		 u-value p
ASD 11 67321 2203 99.43 <0.001 429.07 324.45 533.69 1765.58
Gender Males 4 12223 287 99.09 <0.001 503.53 247.72 759.35 0.258 0.612
Females 4 10842 160 98.49 <0.001 294.22 123.97 464.48
Area Urban 4 29124 479 99.25 <0.001 141.74 50.67 232.81 0.023 0.88
Rural 1 6796 34 - - 50.03 33.26 66.80
Study time 2009-2012 3 14370 1190 99.22 <0.001 1149.51 532.33 1766.69 8.651 0.003
2013-2014 4 34533 575 99.58 <0.001 188.30 87.97 288.63
Study site East of China 8 46187 1586 99.46 <0.001 494.32 362.42 626.23 0.286 0.593
Central China 3 21134 617 99.45 <0.001 290.11 47.37 532.84
Screening tools CABS 5 35580 1396 99.63 <0.001 422.06 219.60 624.51 0.524 0.769
CAST 1 701 35 - 0.012 499.29 338.06 660.52
CHAT 5 31040 772 99.33 <0.001 431.86 268.90 594.83
Age (years) <=4 5 29158 1536 99.37 <0.001 530 260 1040 10.653 0.001
>4 3 22428 192 96.93 <0.001 80 30 190
Autism 22 223189 4467 99.60 <0.001 252.84 216.10 289.57 5245.70
Gender Males 12 53265 2156 99.28 <0.001 377.25 264.79 354.82 0.924 0.336
Females 12 46841 1120 98.53 <0.001 247.89 188.23 307.54
Study time 1996-2006 6 42116 177 99.81 <0.001 39.17 11 71 19.013 <0.001
2007-2014 9 70378 1503 99.91 <0.001 349.82 216.66 482.98
Study site East of China 14 177279 3436 99.73 <0.001 260.11 213.92 306.29 2.241 0.524
West of China 4 23942 262 97.49 <0.001 149.78 92.40 207.16
Central China 3 21968 769 98.4 <0.001 334.73 151.68 517.78
Screening tools ABC 4 46116 684 98.86 <0.001 136.67 44.47 228.87 0.791 0.673
CABS 14 138768 3136 99.65 <0.001 268.94 213.49 324.39
CHAT 4 38305 647 99.46 <0.001 406.73 115.76 697.70
Age (years) ≤3.58 5 23170 794 98.77 <0.001 290 140 590 0.567 0.451
>3.58 4 51439 3018 99.54 <0.001 440 200 950
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Screen tools: ABC, Autism Behavior Checklist; CABS, Clancy Autism Behavior Scale; CARS, Childhood Autism Rating Scale; CHAT, Checklist for Autism in Toddlers; CAST, Children Autism Spectrum Test

Prevalence of autism

Prevalence of autism based on clinical diagnostic criteria

The pooled prevalence of autism from 25 studies with available data was 10.18 per 10,000 (95% CI: 8.46-11.89 per 10,000, I2=92.5%) (Figure 2b). The prevalence of autism in males (20.50 per 10,000) was higher than in females (6.12 per 10,000). The prevalence of autism in urban areas was around 2 folds higher than in rural areas (14.80 per 10,000 vs. 6.06 per 10,000). The prevalence of autism from studies conducted after 2008 was higher than those in or before 2008 (20.40 per 10,000 vs. 8.18 per 10,000). The prevalence of autism between the eastern, western and central China showed some variation (14.62 per 10,000 vs. 6.41 per 10,000 vs. 8.68 per 10,000). The prevalence of autism in the group of children aged ≤2.08 years (40 per 10,000) was significantly higher than those aged >2.08 years (20 per 10,000). With the exception of one study reporting a low prevalence (2.96 per 10,000) using the DSM-3, there was no difference in prevalence of autism between other diagnostic criteria (14.78 per 10,000 using ABC, 10.05 per 10,000 using CCMD, 17.03 per 10,000 using DSM-4, and 10.14 per 10,000 using ICD-10) (Table 2).

Prevalence of autism based on screening tools

The pooled prevalence of autism from 22 studies with available data was 252.84 per 10,000 (95% CI: 216.1-289.57 per 10,000, I2=99.5%) (Figure 3B). The prevalence of autism in males (377.25 per 10,000) was higher than in females (247.89 per 10,000). The prevalence of autism from studies conducted in and before 2006 was 39.17 per 10,000, while those done after 2006 had increased to 349.82 per 1000. The prevalence of autism in central China (334.73 per 10,000) was higher than eastern China (260.11 per 10,000) and western China (149.78 per 10,000). The prevalence of autism was different between the two age groups (290 per 10,000 in those aged ≤3.58 years; 440 per 10,000 aged > 3.58 years). Significant difference in the prevalence of autism between different screening tools was observed (136.67 per 10,000 using ABC; 268.94 per 10,000 using CABS; 406.73 per 10,000 using CHAT) (Table 3).

Sensitivity analysis and publication bias

The sensitivity analyses did not find any individual studies that significantly influence the overall results in each diagnostic group. Egger's test revealed publication bias for ASDs (ASDs: t=2.33, P=0.036), but not for autism (t=1.506, P=0.143).

Discussion

This comprehensive meta-analysis of the pooled prevalence of ASDs and autism included 44 studies with 2,337,321 subjects in China covering 30 of the 34 provinces/ municipalities/ autonomous regions of the country. The large variation in prevalence between studies is probably due to methodological differences in sampling methods and screening tools or diagnosis criteria used. This meta-analysis found that the pooled prevalence of ASD based on clinical diagnostic criteria was 39.23 per 10,000, which is lower than in other countries worldwide. For example, Duchan et al. 14 found that the prevalence of ASDs was 60 per 10,000 in North America. In Europe, the median rate of ASD was 61.9 per 10,000 15, while in the USA the prevalence of ASD was 110 per 10,000 16. Further, in Asia the figure was 264 per 10,000 in South Korea 17 and 181 per 10,000 in Japan 18.

On the other hand, the pooled prevalence of autism of 10.18 per 10,000 established by clinical diagnostic criteria was similar to the systemic review of 24 studies in China (12.8 per 10,000) 9 and another meta-analysis of 18 studies (11.8 per 10,000) 10. Although significant heterogeneity between studies (I2=92.5%) was noted, sensitivity analyses did not find any outlying studies that significantly affect the overall results in each diagnostic group.

Screening tools on ASDs and autism have been widely used in epidemiological surveys globally. Based on such screening tools, in this study the prevalence of ASDs ranged from 33 per 10,000 to 1853.3 per 10,000 with the pooled figure of 429.07 per 10,000, while the prevalence of autism ranged from 10 per 10,000 to 1259.8 per 10,000 with the pooled figure of 252.84 per 10,000. The CABS was the most commonly used screening tool for autism in China 19, but rarely used in Western studies. In contrast, the ADOS and Autism Diagnostic Interview- Revised (ADI-R) were widely used in Western studies. In addition, the ADOS and ADI-R included more information than the CABS. Thus, the discrepancy in screening tools used for ASDs and autism could partly explain the different findings between Chinese and Western studies 10.

Previous studies found that the prevalence of ASD and autism established by clinical diagnostic criteria in males was 3-4 times higher than in females 20, 21, which is consistent with the results of our study. We also found that the pooled prevalence of autism in urban areas was significantly higher than in rural areas, which is concordant with the urban/rural rates in other developed countries, such as in the USA 22. Various environmental stressors 23, such as prenatal exposure to environmental stress 24 and lower parental education 16 may partly lead to the urban/ rural difference. However, the urban /rural difference was not found in the prevalence of ASDs in this study.

Children aged 2-6 years had the highest prevalence of ASDs in previous surveys. This study found that the age group ≤4 years had a higher prevalence (530 per 10,000) than the group > 4 years (80 per 10,000), which is not consistent with the findings (the highest risk in children aged 4-6 years) in a national survey in China 25. In China children with ASDs are usually sent to special schools, which may result in an underestimated prevalence of ASDs in school age children in epidemiological surveys. Further, screening tools that have been widely used in China, such as the CABS, were originally designed to be completed by parents 26. Parents may wish to avoid the diagnosis of autism or hoped that the symptoms would be reversed in their children, which may lead to an underestimation in self-reported surveys 7. All these factors could contribute to the relatively lower prevalence of ASDs in school age groups 27.

The prevalence of autism based on clinical diagnostic criteria in studies done before the year 2008 (8.18 per 10,000) was significantly lower than that after 2008 (20.4 per 10,000), which was consistent with previous findings 14. However, the trend appeared to be the opposite in the prevalence of ASDs (38.72 per 10,000 in and before 2012, and 36.36 per 10,000 after 2012). The discrepancy in findings across study period may be related to differences in diagnostic criteria and qualification of interviewers. In addition, children with ASDs usually present with complex symptoms, which could lead to inaccurate diagnosis 28. The improvement of standardized interview and diagnostic instruments could partly explain the increased prevalence of autism over time.

The results need to be interpreted with caution due to several limitations. First, heterogeneity was present even in subgroup analyses although such heterogeneity is difficult to avoid in epidemiological studies 29. Second, different screening instruments and diagnostic criteria were used across studies. In order to reduce the relevant heterogeneity, subgroup analyses between different screening instruments and diagnostic criteria were conducted. Third, the 44 studies in this meta-analysis covered 30, but not all the 34 provinces/municipalities/autonomous regions in China. Finally, relevant factors on the prevalence of ASDs, such as socioeconomic and environmental variables, were not recorded in the majority of papers, therefore their impact could not be examined.

In conclusion, the prevalence estimates of ASDs and autism are generally lower in China than in other countries worldwide. Further epidemiological studies with stringent methodology are needed to clarify the variation in prevalence.

Acknowledgments

The study was supported by the University of Macau (MYRG2015-00230-FHS; MYRG2016-00005-FHS) and the Shenzhen Science and technology Innovation Committee (JCYJ 20160429185235132).

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