Downie Lilian, Halliday Jane, Lewis Sharon, Amor David J
Murdoch Children's Research Institute, Melbourne, Victoria, Australia.
Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia.
JAMA Netw Open. 2021 Jul 1;4(7):e2114336. doi: 10.1001/jamanetworkopen.2021.14336.
Genomic newborn screening (gNBS) may optimize the health and well-being of children and families. Screening programs are required to be evidence based, acceptable, and beneficial.
To identify what has been discovered following the reporting of the first gNBS pilot projects and to provide a summary of key points for the design of gNBS.
A systematic literature review was performed on April 14, 2021, identifying 36 articles that addressed the following questions: (1) what is the interest in and what would be the uptake of gNBS? (2) what diseases and genes should be included? (3) what is the validity and utility of gNBS? and (4) what are the ethical, legal, and social implications? Articles were only included if they generated new evidence; all opinion pieces were excluded.
In the 36 articles included, there was high concordance, except for gene disease inclusion, which was highly variable. Key findings were the need for equitable access, appropriate educational materials, and informed and flexible consent. The process for selecting genes for testing should be transparent and reflect that parents value the certainty of prediction over actionability. Data should be analyzed in a way that minimizes uncertainty and incidental findings. The expansion of traditional newborn screening (tNBS) to identify more life-threatening and treatable diseases needs to be balanced against the complexity of consenting parents of newborns for genomic testing as well as the risk that overall uptake of tNBS may decline. The literature reflected that the right of a child to self-determination should be valued more than the possibility of the whole family benefiting from a newborn genomic test.
The findings of this systematic review suggest that implementing gNBS will require a nuanced approach. There are gaps in our knowledge, such as the views of diverse populations, the capabilities of health systems, and health economic implications. It will be essential to rigorously evaluate outcomes and ensure programs can evolve to maximize benefit.
基因组新生儿筛查（gNBS）可能会优化儿童及其家庭的健康和福祉。筛查项目必须基于证据、可接受且有益。
确定在首个gNBS试点项目报告之后所发现的情况，并总结gNBS设计的要点。
于2021年4月14日进行了一项系统的文献综述，确定了36篇涉及以下问题的文章：（1）对gNBS的兴趣以及其接受程度如何？（2）应纳入哪些疾病和基因？（3）gNBS的有效性和实用性如何？以及（4）伦理、法律和社会影响是什么？仅纳入产生新证据的文章；所有观点性文章均被排除。
在所纳入的36篇文章中，除了基因疾病的纳入情况差异很大外，其他方面的一致性较高。主要发现包括需要公平获取、合适的教育材料以及知情且灵活的同意。选择检测基因的过程应透明，并反映出父母更看重预测的确定性而非可操作性。数据的分析方式应尽量减少不确定性和偶然发现。将传统新生儿筛查（tNBS）扩展以识别更多危及生命且可治疗的疾病，需要与让新生儿父母同意进行基因组检测的复杂性以及tNBS总体接受率可能下降的风险相平衡。文献表明，儿童的自决权应比整个家庭从新生儿基因组检测中受益的可能性更受重视。
这项系统综述的结果表明，实施gNBS将需要一种细致入微的方法。我们在知识方面存在差距，例如不同人群的观点、卫生系统的能力以及健康经济影响。严格评估结果并确保项目能够不断发展以实现利益最大化至关重要。
