National Study on Autism Spectrum Disorder in China
Condition: Autism Spectrum Disorders
MeSH terms: Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive
Study type: Observational

Summary: 
      The aims of the national population-based study on Autism Spectrum Disorder (ASD) include:
      (1) to understand the overall prevalence of ASD in children aged 6-12 years in 8 cities
      (n=120,000), (2) to explore environmental and genetic risk factors associated with ASD
    

Detailed description: 
      The study is a multicenter, cross-sectional study involing eight cities. The program includes
      a prevalence study and a risk factors analysis.

        1. Prevalence study on ASD To estimate the national prevalence of ASD in Chinese pediatric
           population aged 6-12 years.

           1.1. Target population This 4-year study is initiated in the year of 2013 in eight
           cities of China . For each city, 3 communities with different economic levels were
           chosen including all children born within Jan 2001 to Dec 2007 (ages 6-12 years at
           screening) with local residency or have lived in the community over 6 months. The ASD
           children who are attending special education schools and meet with the inclusion
           criteria will also be included in the prevalence estimation.

           1.2. Sample size Based on the previous regional studies , we plan to recruit approx.15,
           000 subjects for each city (average. 5,000 subjects for each community), and 120,000
           subjects in total then comprise the national study sample. The plan will be updated,
           based on the prevalence obtained in the pilot study.

           1.3. Screening and diagnosis The screening tool will be chosen from Autism Spectrum
           Rating Scale (ASRS) or SRS（Social Responsiveness Scale） after pilot study.The
           questionnaire is a parent-administered form that takes approximately 15-20 minutes to
           complete. Parents of recruied children were invited to complete the questionnaire.
           Parents of all questionnaire screen-positive children will be contacted for appointing
           further diagnostic evaluations. Children whose parents could not be reached are
           classified as non-responders. The DSM-Ⅳ, ADI-R and ADOS (ADI-R: Autism Diagnosis
           Interview-Revised, ADOS: Autism Diagnosis Observation Scales) are used for diagnostic
           evaluations. Co-morbidities, such as epilepsy and ADHD (Attention Deficit Hyperactivity
           Disorder )after aditional medical examinations such as, EEG(electroencephalogram), head
           circumference, anthropometrics, allergies, sleep patterns, etc.

        2. Risk Factors study on ASD A classic case-control design is applied to explore the risk
           factors of ASD. 2.1. Study subjects 2.1.1. Cases and control Cases were children living
           in target communities who are identified as positive based on questionnaire screen and
           the subsequent diagnosis with DSM-Ⅳ, ADOS and ADI-R.

      Controls were children who are screened to be negative and matched to cases by age, gender,
      and class.

      2.2. Environmental pollutants exposures Given the hypothesis that environmental factors might
      play a role in the etiology of ASD, we will analyze the biological samples of the subjects to
      investigate environmental exposures including chronic lead exposure, pesticides exposure, and
      endocrine disruptors exposure , for which, hair, blood, and urine will be collected for cases
      and controls. The detailed protocol for the measurement of each kind of biological sample has
      been introduced everywhere (see the references in individual block).

      2.3. Analysis of other potential risk factors This study will also analyze the association
      between the onset of ASD and other risk factors, including diet (), living
      environment(),perinatal characteristics of parents, feeding history, baby growth and
      development after birth by using questionnaire and reviewing medical records.

      2.4. Genetic analysis We are going to use the targeted area capture technology developed
      before and HiSeq2000, the second generation of high throughput sequencing platform, to carry
      out the molecular diagnosis screening (monogenic disease). Also, we will screen through Trio
      those ASD-related genetic mutations that are of high credibility and occur frequently so as
      to classify ASDs according to their definite etiologies.Furthermore, we will continue the
      study on the distribution of ASD relevant gene mutations among patients in China, which will
      lay a solid foundation for further studies of molecular epidemiology.Meanwhile, we will also
      apply genome-wide sequencing technology on the positive cases so as to find new mutation that
      might serve as potential molecular markers facilitating the diagnosis and treatment of ASDs.

      A pilot study involving 4 cities (n=400 for each, in total n>=1600)will be conducted to test
      all methodology that will be applied in the prevalence study. A diagnostic study will be
      performed to evalute the performance of ASRS and SRS in screening ASD, one of which will be
      applied in the main study.
    

Observational model: Other
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Community-based populations aged 6-12 years old form 8 cities in China
      
Biospecimen description: 
      whole blood 2*5ml, (isolate Plasma, Serum and white cell) Hair, Urine(biosample will be
      collected only for Cases 1200 +Controls 1200)
    
Keywords: Autism spectrum disorders; Prevalence; Diagnosis; Screen; Risk Factor; SRS; ASRS