Clinical vs. community sample
For earlier detection and diagnosis, the American Academy of Pediatrics guidelines recommend routine ASD-specific and standardized developmental screening surveillance of every child. However, a nationwide community screening of the association between parental stress and children with ASD and developmental delay showed that mothers who had perceived better physical health and quality of life had increased concern that their children had ASD. This is inconsistent with clinical findings showing that taking care of children with ASD increases the stress of both parents,7 and mothers of children with ASD, developmental delay and intellectual disability also suffer greater stress and depression than mothers of healthy children.8,9 This community study showed different results from previous studies; however, using the Resiliency Model of Family Stress, Adjustment, and Adaptation,10 Twoy, Connolly and Novak investigated the coping strategies of parents of children with ASD, and found that Asian-Americans were more readily able to hold an optimistic view when facing the stresses of ASD, due to their religion and philosophical beliefs, and to find solutions to problems and see the stressor simply as a fact of life.11 Another study also found that mothers of adults with intellectual disability were able to adapt, and thus had better self-perceived health than the controls.12 We can also hypothesize that in clinical cases, parents may have sought help because those children were exhibiting more disruptive behaviors or symptoms, thus causing greater distress to the mothers; this would result in a biased health-worker effect, wherein all mothers of children with ASD would be observed as having greater distress.
Therefore, ASD screening tools that can be used in primary care and community settings are vital. In the community, instruments that can be completed without professional training and that are short and easily comprehensible are needed. Community screening instruments are not only helpful to the public in heightening understanding of their children’s developmental condition, they may also aid doctors in their decision-making process. Furthermore, for clinicians to interpret positive predict values (PPV) and negative predictive values (NPV) appropriately, they have to comprehend the estimated prevalence of the condition in their particular population.13 Hence, to understand the idea of spectrum in the ASD diagnosis in the DSM-5, we not only need to understand the etiology of ASD, but also the trajectory and norm of children's development.
Application of two-stage window screening in the community
For early detection and large-scale screening in the community, two-stage screening methods are often used. A two-stage screening process involves using a more inexpensive, less invasive test at the first stage (e.g., Modified Checklist of Autism in Toddlers [M-CHAT]), and a more expensive or more invasive, but more sensitive and specific test at the second stage (e.g., Autism Diagnostic Inventory - Revised [ADI-R]).14 Chien, Huang and Lung proposed the two-stage window screening method, a more efficient screening method.15 This screening method can be used in settings where the screening sample is larger in size, such as the community or primary care settings.16 Two cutoff points are needed in the first stage of the two-stage window screening, yielding three groups. Those in the first (highest scoring) group are normal (assuming higher scores are better), and those in the third (lowest) group have the highest risk for the disorder; therefore, they can be directly scheduled for diagnostic assessment (e.g., ADI-R). Participants in the middle group, between the two cutoff points, have the highest probability of being misclassified and need to be screened further using a more specific screening instrument (e.g., M-CHAT). A lower number of people need to be screened in the second stage using this method, decreasing the cost of testing.15,16 Lung and colleagues used the eight-item Parental Concern Checklist (PCC) as the first-stage screening instrument in a two-stage window screening method. With the cutoff points of 2/3 and 6/7, the PCC can differentiate three distinctively different developmental groups.16 Participants in the borderline group (scores from three to six on the PCC) would be administered a more specific screening instrument (such as the M-CHAT) at the second stage to decide if they need a more invasive assessment. Participants with the greatest risk (scores seven and eight on the PCC) should be directly scheduled for a more invasive and detailed diagnostic assessment.16 After four years, when the children were 66 months old, the NPV of the PCC remained high at 99.67% (Table 1), showing that those that were not screened out at 18 months were not likely to be diagnosed at 66 months. In the traditional method of positive or negative two-stage screening, all those scoring higher than the cutoff point need to be tested at the second stage. Fewer people need to be assessed in the second stage using the two-stage window screening, which decreases the cost of testing15 and the number of false positives.16
Table 1
The application of the two-stage window screening method in screening of children using Parental Concern Checklist (PCC) at 18-months and rate of diagnosis with autism spectrum disorder at 5.5 years old
| ASD | Not diagnosed | Total | |
PCC 3–6 | 25 | 2615 | 2640 | PPV: 25/2640 = 0.95% |
others | 63 | 18960 | 19023 | NPV: 18960/19023 = 99.67% |
Total | 88 | 21575 | 21663 | |
| Sensitivity 25/88= 28.41% | Specificity 18960/21575= 87.87% | | |
PPV: positive predictive value; NPV: negative predictive value |
The two-stage window screening method was applied in another study using the Taiwan Birth Cohort Study Developmental Instrument (TBCS-DI) as the first-stage screening instrument and the M-CHAT as the lead criteria for screening of ASD at six, 18, and 36 months.17 Eighteen percent of the children were screened out as being at high risk for ASD, and the cutoff points of 65/66, 42/43, and 51/52, were found for the TBCS-DI six-, 18-, and 36-month scales, respectively, with NPVs of 83.44%, 84.21%, and 85.35%, showing that the TBCS-DI can be used as a broadband screening instrument for ASD in a community-based setting.17 Although the NPVs of the TBCS-DI were found to be high (above 80%), the PPVs were low (19%, 21%, 25% for six, 18, and 36 months respectively).17
In addition, when the children were 66 months old (four years later), the NPV of the TBCS-DI was still at 99.81% (Table 2). It should be noted that both the TBCS-DI and PCC involve parental reports of their children's development. However, the PCC deals with parental concerns and the TBCS-DI with the children's developmental milestones. Although they are both first-stage screening instruments, they carry the risk of over-referral18 and may increase the apparent prevalence of disorders, with a high possibility of false positives. This may be especially true in the case of the PCC, because the questions relate to concerns that a parent might have regarding their child’s development. Unlike clinical research, low PPVs are accepted in community research because the threshold for failing the screening was set low to prevent as many misses as possible at the expense of the PPVs. For clinical research, the prevalence is set at 50% (control vs. clinical groups), and is not reflective of the real prevalence of the disorder. Therefore, even though low PPVs may bring about a high rate of false positives, causing over-referrals in the community, a study showed that those who screen out as false positives in developmental screening perform substantially worse than the true-negatives in standardized testing, and show greater psychosocial risks.19 For that reason, early intervention for those screened out as false positives as a preventive strategy is still needed when permitted, since it can ameliorate later stigmatization.
Table 2
The application of the two-stage window screening method in screening of children using Taiwan Birth Cohort Study- Developmental Instrument (TBCS-DI) at 18-months and rate of diagnosis with autism spectrum disorder at 5.5 years old
| ASD | Not diagnosed | Total | |
TBCS-DI | 54 | 3763 | 3817 | PPV: 54/3817 = 1.41% |
others | 34 | 17812 | 17846 | NPV: 17812/17846 = 99.81% |
Total | 88 | 21575 | 21663 | |
| Sensitivity 54/88= 61.36% | Specificity 17822/21575= 82.60% | | |
PPV: positive predictive value; NPV: negative predictive value |
Children's developmental trajectory
The Taiwan Birth Cohort Study (TBCS) aimed to develop a nationally representative cohort database to establish national norms. Using national household probability sampling method with no exclusion criteria, all babies born in Taiwan in 2005 were eligible for inclusion in the TBCS. A total of 21,248 families (11.7% selection rate) participated when the children were 6 months old; 20,172 families agreed to be followed up (95%) at 18 months; 19,910 (94%) at 36 months; 19,721 (93%) at 66 months; and finally, 19,516 (92%) families were followed up when the children were eight years old.20 Using a dataset of the development of 11,145 babies from six to 66 months selected nationwide as a basis, the developmental trajectory of the children in the four dimensions of gross motor, fine motor, language, and social dimensions can be illustrated (Fig. 1). The procedures of the study have been approved by a teaching hospital in Taiwan. The growth trajectory showed children's language development began to incline at 18 months, and peaked at 36 months. On the other hand, children's social development showed a steady growth from 18 to 66 months. This is congruent with previous studies that showed at an early age, when children's language development is increasing, the pathological language patterns of children with ASD are categorized into the stereotyped behavior dimension, and as children grow older, and compared to the social development of normally developing children, their language dysfunction is reflected in the social-communication category.21,22 Furthermore, the increase in the trajectory of children's language development prior to age three, compared to other developmental dimensions, may also increase the difficulty of diagnosis.
Furthermore, due to the Chinese cultural context of collectivism and vertical hierarchical family structure, social harmony is emphasized and greater restraint is exerted over emotional displays than those in individualistic cultures.23 As a consequence, the TBCS-DI intended to separate emotion dimension from the gross motor, fine motor, language and social dimensions at when children were 3 years old but failed. The emotion dimension was only able to be distinguished from other dimensions at when the children were 8-year-old.20 Although the emotion dimension was unable to be distinguished prior to the age of eight, the predictive validity model shows the emotion dimension was a suppressor within the social dimension in earlier scales, supporting the importance of social communication in Asian collectivist culture.23 Differences in emotional development of children in the Chinese culture may also influence the ability to diagnose atypical empathic responses in children with ASD,24 which has been shown to be contributed by epigenetics and the interaction between environ-mental factors and genetic susceptibilities.25