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. 2023 Sep 5;6(9):e2331162.
doi: 10.1001/jamanetworkopen.2023.31162.

Genomic Sequencing as a First-Tier Screening Test and Outcomes of Newborn Screening

Ting Chen  1 , Chunna Fan  2   3   4 , Yonglan Huang  5 , Jizhen Feng  6 , Yinhong Zhang  7 , Jingkun Miao  8 , Xiaohua Wang  9 , Yulin Li  10 , Cidan Huang  11 , Weiwei Jin  2   3 , Chengfang Tang  5 , Lulu Feng  6 , Yifan Yin  8 , Bo Zhu  9 , Meng Sun  10 , Xiulian Liu  11 , Jiale Xiang  2 , Minyi Tan  5 , Liyun Jia  6 , Lei Chen  2 , Hui Huang  2 , Huanhuan Peng  2 , Xin Sun  1 , Xuefan Gu  1 , Zhiyu Peng  2 , Baosheng Zhu  7 , Hui Zou  10 , Lianshu Han  1
Affiliations

Genomic Sequencing as a First-Tier Screening Test and Outcomes of Newborn Screening

Ting Chen et al. JAMA Netw Open. .

Abstract

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.

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Conflict of interest statement

Conflict of Interest Disclosures: None reported.

Figures

Figure.
Figure.. Study Flowchart
G6PD indicates glucose-6-phosphate dehydrogenase; HTT, hyperthyrotropinemia; NBS, newborn screening.
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References

    1. Therrell BL, Padilla CD, Loeber JG, et al. . Current status of newborn screening worldwide: 2015. Semin Perinatol. 2015;39(3):171-187. doi:10.1053/j.semperi.2015.03.002 - DOI - PubMed
    1. van Spronsen FJ, Blau N, Harding C, Burlina A, Longo N, Bosch AM. Phenylketonuria. Nat Rev Dis Primers. 2021;7(1):36. doi:10.1038/s41572-021-00267-0 - DOI - PMC - PubMed
    1. Chace DH, Kalas TA, Naylor EW. The application of tandem mass spectrometry to neonatal screening for inherited disorders of intermediary metabolism. Annu Rev Genomics Hum Genet. 2002;3:17-45. doi:10.1146/annurev.genom.3.022502.103213 - DOI - PubMed
    1. Kwon C, Farrell PM. The magnitude and challenge of false-positive newborn screening test results. Arch Pediatr Adolesc Med. 2000;154(7):714-718. doi:10.1001/archpedi.154.7.714 - DOI - PubMed
    1. Biesecker LG, Green RC. Diagnostic clinical genome and exome sequencing. N Engl J Med. 2014;370(25):2418-2425. doi:10.1056/NEJMra1312543 - DOI - PubMed

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