**2.5 Verification of new screening tools for neurodevelopmental disorders in 5-year-old children**

We analyzed multiple questionnaires completed by the parents and teachers of 954 5-year-old primary screening participants in 2013 and the DSM-5 diagnoses of 156 individuals who participated in the secondary examination, then we invented an algorithm to extract the NDD risk group. Children were considered "screen positive" if one of the following criteria (a)–(d) was met:


#### **Figure 6.**

 *Comparison the proportion of NDDs high-risk children with old and new algorithm.* 


#### **Table 3.**

 *Old algorithm and new algorithm.* 

 We validated the algorithm on 965 people in 2014, 1004 people in 2015, 1031 people in 2016, 967 people in 2017, and 1040 people in 2018. The confirmation method is as follows.

 First, we compared the rate of high-risk group extraction for her NDD by year under the old and new algorithms (see **Figure 6** ). **Table 3** shows old algorithm and new algorithm.

 Next, we compared between the proportion of children with special needs who diagnosed with NDD, those who were below the diagnostic criteria but required observation and had no problems by year (see **Figure 7** ). Finally, we calculated the

**Figure 7.** *Changes in the rate of children who need supports and observation, or no needs.*

sensitivity and specificity of the new algorithm for extracting children with special needs and observation needs, which were 0.89 and 0.99, respectively.

The new algorithm, created by combining multiple tests, has made it possible to extract risk children more efficiently than the old algorithm. This algorithm was put into a web system in 2019, and from 2020 it was used in developmental health checkups in Hirosaki City [31]. Due to the spread of COVID-19, it was difficult to hold face-to-face health checkups, but with the introduction of the web system, the participation rate of 5-year-old developmental health checkups increased from 85–94%, and the secondary health checkup rate also increased. As a result, more children with NDD are receiving support for adjusting to primary school than before.

### **3. Conclusions**

Epidemiological research in medium-sized cities in northern Japan will soon reach its 10th anniversary. Epidemiological studies are carried out as observational studies over time, repeating the same methods as much as possible. In Japan, where early detection is delayed, intervention support is provided after investigation and diagnosis. It had to be used for individual profit. Although this study reported an analysis of a 4-year survey, a 10-year trajectory and prognostic study of NDD diagnosis in 5-year-olds will begin in the future. We hope that our research will continue and help build a comfortable society for NDD.

#### **Acknowledgements**

We would like to express our heartfelt gratitude to all children, their families, teachers, and Hirosaki City staff who participated in HFC study and the Hirosaki University faculty members and researchers (Hirota T, Sakamoto Y, Mikami T,

Terui A, Osato A, Koeda S, Mikami M, Kuribayashi M, and Nakamura K) who were involved in the examination, diagnosis, and statistical analysis of health checkups.

This study was supported by the following grants: Grants-in-Aid for Scientific Research (KAKENHI: grant numbers JP16K10239 and JP19K08062), Hirosaki City Commissioned Research Fund, Hirosaki University Institutional Research Grant for Future Innovation, Industry-Academia Joint Development Research Fund, and Hirosaki Institute of Neuroscience in Japan.
