SeqFirst: Building equity access to a precise genetic diagnosis in critically ill newborns.

IF 8.1 1区 生物学 Q1 GENETICS & HEREDITY
American journal of human genetics Pub Date : 2025-03-06 Epub Date: 2025-02-24 DOI:10.1016/j.ajhg.2025.02.003
Tara L Wenger, Abbey Scott, Lukas Kruidenier, Megan Sikes, Alexandra Keefe, Kati J Buckingham, Colby T Marvin, Kathryn M Shively, Tamara Bacus, Olivia M Sommerland, Kailyn Anderson, Heidi Gildersleeve, Chayna J Davis, Jamie Love-Nichols, Katherine E MacDuffie, Danny E Miller, Joon-Ho Yu, Amy Snook, Britt Johnson, David L Veenstra, Julia Parish-Morris, Kirsty McWalter, Kyle Retterer, Deborah Copenheaver, Bethany Friedman, Jane Juusola, Erin Ryan, Renee Varga, Daniel A Doherty, Katrina Dipple, Jessica X Chong, Paul Kruszka, Michael J Bamshad
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引用次数: 0

Abstract

Access to a precise genetic diagnosis (PrGD) in critically ill newborns is limited and inequitable because the complex inclusion criteria used to prioritize testing eligibility omit many patients at high risk for a genetic condition. SeqFirst-neo is a program to test whether a genotype-driven workflow using simple, broad exclusion criteria to assess eligibility for rapid genome sequencing (rGS) increases access to a PrGD in critically ill newborns. All 408 newborns admitted to a neonatal intensive care unit between January 2021 and February 2022 were assessed, and of 240 eligible infants, 126 were offered rGS (i.e., intervention group [IG]) and compared to 114 infants who received conventional care in parallel (i.e., conventional care group [CCG]). A PrGD was made in 62/126 (49.2%) IG neonates compared to 11/114 (9.7%) CCG infants. The odds of receiving a PrGD were ∼9 times greater in the IG vs. the CCG, and this difference was maintained at 12 months follow-up. Access to a PrGD in the IG vs. CCG differed significantly between infants identified as non-White (34/74, 45.9% vs. 6/29, 20.7%; p = 0.024) and Black (8/10, 80.0% vs. 0/4; p = 0.015). Neonatologists were significantly less successful at predicting a PrGD in non-White than non-Hispanic White infants. The use of a standard workflow in the IG with a PrGD revealed that a PrGD would have been missed in 26/62 (42%) infants. The use of simple, broad exclusion criteria that increase access to genetic testing significantly increases access to a PrGD, improves access equity, and results in fewer missed diagnoses.

SeqFirst:为重症新生儿的精确基因诊断提供公平机会。
危重新生儿获得精确基因诊断(PrGD)的机会有限且不公平,因为用于确定检测资格的复杂纳入标准忽略了许多遗传疾病高风险患者。SeqFirst-neo是一个程序,用于测试基因型驱动的工作流程是否使用简单、广泛的排除标准来评估快速基因组测序(rGS)的资格,从而增加危重新生儿获得PrGD的机会。对2021年1月至2022年2月期间入住新生儿重症监护病房的所有408名新生儿进行了评估,在240名符合条件的婴儿中,126名婴儿接受了rGS(即干预组[IG]), 114名婴儿同时接受了常规护理(即常规护理组[CCG])。在62/126 (49.2%)IG新生儿中进行了PrGD,而在11/114 (9.7%)CCG婴儿中进行了PrGD。IG组接受PrGD的几率是CCG组的9倍,这种差异在12个月的随访中保持不变。非白种人婴儿在IG和CCG中获得PrGD的机会差异显著(34/ 74,45.9% vs. 6/ 29,20.7%;p = 0.024)和Black (8/10, 80.0% vs. 0/4;P = 0.015)。新生儿科医生在预测非白人婴儿的PrGD方面的成功率明显低于非西班牙裔白人婴儿。在IG中使用标准的PrGD工作流程显示,有26/62(42%)的婴儿遗漏了PrGD。使用简单、广泛的排除标准增加了获得基因检测的机会,大大增加了获得PrGD的机会,提高了获得公平,并减少了漏诊。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
14.70
自引率
4.10%
发文量
185
审稿时长
1 months
期刊介绍: The American Journal of Human Genetics (AJHG) is a monthly journal published by Cell Press, chosen by The American Society of Human Genetics (ASHG) as its premier publication starting from January 2008. AJHG represents Cell Press's first society-owned journal, and both ASHG and Cell Press anticipate significant synergies between AJHG content and that of other Cell Press titles.
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