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- Title
Genomic Sequencing as a First-Tier Screening Test and Outcomes of Newborn Screening.
- Authors
Chen, Ting; Fan, Chunna; Huang, Yonglan; Feng, Jizhen; Zhang, Yinhong; Miao, Jingkun; Wang, Xiaohua; Li, Yulin; Huang, Cidan; Jin, Weiwei; Tang, Chengfang; Feng, Lulu; Yin, Yifan; Zhu, Bo; Sun, Meng; Liu, Xiulian; Xiang, Jiale; Tan, Minyi; Jia, Liyun; Chen, Lei
- Abstract
Key Points: Question: What are the benefits of applying gene panel sequencing as a first-tier newborn screening test at a population scale? Findings: In this cohort study including 29 601 newborns, gene panel sequencing of 128 diseases as first-tier screening test identified 59 more patients (1 in 500 newborns). Of these, 20 patients were affected by disorders screened by both biochemical and gene panel sequencing and 39 patients were affected by disorders screened solely by gene panel sequencing. Meaning: These results suggest that gene panel sequencing is a promising approach to screen newborns for monogenic disorders and would provide a better outcome when incorporated into the current newborn screening program. This cohort study of Chinese newborns examines the outcomes of gene panel sequencing as a first-tier newborn screening test supplementing biochemical screening for monogenic disorders. Importance: Newborn screening via biochemical tests is in use worldwide. The availability of genetic sequencing has allowed rapid screening for a substantial number of monogenic disorders. However, the outcomes of this strategy have not been evaluated in a general newborn population. Objective: To evaluate the outcomes of applying gene panel sequencing as a first-tier newborn screening test. Design, Setting, and Participants: This cohort study included newborns who were prospectively recruited from 8 screening centers in China between February 21 and December 31, 2021. Neonates with positive results were followed up before July 5, 2022. Exposures: All participants were concurrently screened using dried blood spots. The screen consisted of biochemical screening tests and a targeted gene panel sequencing test for 128 conditions. The biochemical and genomic tests could both detect 43 of the conditions, whereas the other 85 conditions were screened solely by the gene panel. Main Outcomes and Measures: The primary outcomes were the number of patients detected by gene panel sequencing but undetected by the biochemical test. Results: This study prospectively recruited 29 601 newborns (15 357 [51.2%] male). The mean (SD) gestational age was 39.0 (1.5) weeks, and the mean (SD) birth weight was 3273 (457) g. The gene panel sequencing screened 813 infants (2.7%; 95% CI, 2.6%-2.9%) as positive. By the date of follow-up, 402 infants (1.4%; 95% CI, 1.2%-1.5%) had been diagnosed, indicating the positive predictive value was 50.4% (95% CI, 50.0%-53.9%). The gene panel sequencing identified 59 patients undetected by biochemical tests, including 20 patients affected by biochemically and genetically screened disorders and 39 patients affected by solely genetically screened disorders, which translates into 1 out of every 500 newborns (95% CI, 1/385-1/625) benefiting from the implementation of gene panels as a first-tier screening test. Conclusions and Relevance: In this cohort study, the use of gene panel sequencing in a general newborn population as a first-tier screening test improved the detection capability of traditional screening, providing an evidence-based suggestion that it could be considered as a crucial method for first-tier screening.
- Subjects
CHINA; NEWBORN screening; BIOCHEMISTRY; SEQUENCE analysis; CONFIDENCE intervals; HEALTH outcome assessment; GENOMICS; RESEARCH funding; CHI-squared test; DATA analysis software; LONGITUDINAL method
- Publication
JAMA Network Open, 2023, Vol 6, Issue 8, pe2331162
- ISSN
2574-3805
- Publication type
Article
- DOI
10.1001/jamanetworkopen.2023.31162