Based on the present study, it was found that the factors that can potentially influence the support of the people for NBGS were mainly related to personal cognition, education, and family income. Among those who did not support NBGS, 49.34% were highly educated, while 23.03% belonged to the low-educated group. Of the participants supporting NBGS, people with high education credentials accounted for 67.55%, whereas those with low education profiles accounted for only 12.23%. Similarly, in the non-supportive NBGS population, 3.3% had an annual family income of more than 400,000 RMB, and 32.89% had an annual family income of less than 100,000 RMB. Participants with a yearly household income of less than 100,000 RMB accounted for only 13.85% of those who supported NBGS. In contrast, those with an annual household income of more than 400,000 RMB accounted for only 11.83% (Table 4).
Our findings also revealed that for the future clinical development of NBGS, it is critical to do an exceptional job sharing relevant NBGS knowledge. The general public must fully comprehend the importance of NBGS development. We observed that participants preferred to learn passively rather than actively to understand NBGS content (Table 5).
China has unveiled a new policy of three-child per family, which has recommended that a couple can have up to three children. Thus, the importance of the NBGS project is not only to efficiently screen out newborn diseases on time but also to combine it with genetic counselling to guide parents in reproducing, which is crucial in producing healthy children. In addition, we also found that the majority (15.57% vs. 8.55%) of the adults (≥ 35 years old) were willing to support the development of NBGS, which makes us gratified. The benefit of the three-child policy is that the number of advanced maternal age will inevitably increase, while the pregnancy outcomes in older couples have always been a cause for concern [20, 21]. After the project is successfully implemented, older people's support for NBGS will facilitate genetic counselling for advanced maternal age couples.
The actual development of NBGS still needs to go through a relatively long process of exploration, including the specific inclusion of conditions and schemes for the NBGS. Most people believe that more diseases should be included regarding the population's views on the number of diseases screened by NBGS. A small number of people indicated that the suitable amount is enough; this part of the population was also dominated by highly-educated people (Fig. 2), thereby showing a more conservative consideration for supporting the increase in the number of NBGS diseases. The number of diseases that can be screened is limited. As a result, it is crucial to analyze all aspects of the need for early screening, such as the severity of the disease and whether or not it can be treated, because early treatment can improve the prognosis and minimize related morbidity [11, 22, 23]. A strategy for early intervention could potentially generate accurate predictions for disorders affecting infants to children that pose substantial risks but are treatable. Thus, such diseases can be considered the most suitable for the NBGS project inclusion, which will increase the family's program acceptance rate. Simultaneously, care should be taken to avoid including disorders with unknown genotype–phenotype connections, mild phenotypes that may not require intervention, or diseases with late-onset, to avoid the development of "patients in waiting" and the negative effects of overmedicalization [24]. Overmedicalization in this context refers to interventions that are not medically required or evidence-based, which may raise costs and cause concern in these families. The choice of detection technology requires consideration of its cost-effectiveness. In the case of fully considering the national conditions, the detection technology with low cost, simple operation, and short reporting period would be selected [25].
Since the phenotype is not only associated with genotype but also has distinct phenotypic variability, entirely replacing traditional biochemical screening with genetic testing may not be an appropriate screening optimization technique. The organic combination of NBGS and standard biochemical screening may have unexpected effects. The implementation of NBGS requires careful consideration of the above aspects and a comparative analysis of cost-effectiveness before arriving at the best implementation plan that the families ultimately require. In addition, the development of NBGS should also pay attention to ethical issues, especially for genetic counselling, psychological counselling, and carrier information feedback for screen-positive family members. Previous studies have suggested both benefits and risks in feeding information about newborn carriers to newborn families [26, 27]. Nonetheless, we must conduct more appropriate and targeted assessments for different groups and modify the report content based on the evaluation results.
NBGS is a novel concept that has recently been introduced, and it can be considered a significant generation milestone in the field of newborn screening. With the emergence of next-generation sequencing technology, the detection of various inherited diseases is no longer limited to biochemical methods. Thus, analyzing the various diseases from the genetic perspective could help assist in intervention, diagnosis, and treatment. For the best choice of NBGS methods, it is still important to compare and evaluate the cost, detection cycle, DNA coverage, ease of operation, and the population they can be used on. The clinical development of NBGS is also an inevitable trend, but it still needs continuous improvement in the advancement process for everyday use.
We understood the attitudes and beliefs of the reproductive-aged population towards NBGS and found that most individuals were willing to accept NBGS programs. Notably, those with a high level of education and income provide a solid foundation for the future development of NBGS. However, this study also has limitations. The number of male participants was limited, making it difficult to effectively assess the cognitive differences between males and females on many issues.
When "global health" and "social justice" have taken on particular relevance due to the COVID 19 pandemic and vaccine processes, the development of NBGS seems more controversial. In light of current findings, people are motivated to improve the existing NBS on the one hand because they foresee future improvements in their quality of life. The cost of NBGS testing, on the other hand, may hinder the development of NBGS in countries with low-income and lower literacy rates. Yet, the development of NBGS may be reasonably simple and easy for high-income countries and for educated people who understand its importance for the family in the longer term. However, if we want to carry out NBGS in low- and middle-income countries, the income level of low- and middle-income people still needs to be mainly considered, which comprises most of the population. As a middle-income country with a large population, China should consider three leading solutions: (i) improving testing technology to reduce testing costs, (ii) improving the part of medical insurance for NBS, and (iii) giving appropriate government subsidies until the program has been highly accepted and appreciated by the community. The experience and results obtained in implementing and developing NBGS in China may provide reference and help develop NBGS in other developing countries. Prenatal and postnatal care should be paid more attention to the long-term development of human beings. The smooth development of NBGS can improve the screening efficiency of newborn genetic diseases, early detection, and early treatment, providing fertility guidance for the family of the patient children and enhancing the fertility rate. The experience of China's NBGS can also be used for research in other countries to promote global health as a model study.