Department of Pediatrics, Division of Pulmonary and Sleep Medicine, University of Washington, Seattle, Washington, USA.
Center for Respiratory Biology and Therapeutics, Seattle Children's Research Institute, Seattle, Washington, USA.
Pediatr Pulmonol. 2024 Nov;59(11):2901-2909. doi: 10.1002/ppul.27155. Epub 2024 Jun 28.
Newborn screening (NBS) for cystic fibrosis (CF) is universal in the United States. Protocols vary but include an immunoreactive trypsinogen (IRT) level and CFTR variant panel. California CF NBS has a 3-step screening: IRT level, variant panel, and CFTR sequencing if only one variant identified on panel.
This was a cohort study of infants with CF born in California (2007-2021) to examine racial and ethnic differences in having a false-negative NBS result for CF and at which step the false-negative occurred. We examined how different CFTR variant panels would improve detection of variants by race and ethnicity: original 39-variant panel, current 75-variant panel, and all 402 disease-causing CFTR variants in the CFTR2 database.
Of the 912 infants born in California with CF, 84 had a false-negative result: 38 due to low IRT level and 46 with a high IRT value (but incomplete variant detection). Asian (OR 6.3) and Black infants (OR 2.5) were more likely to have a false-negative screening result than non-Hispanic white infants. The majority of false-negative screening (but CF diagnosis) cases among American Indian/Native Alaskan and non-Hispanic White infants were due to low IRT levels. The majority of Asian and Hispanic infants with false-negative screening had no variants detected. Detection of two CFTR variants was improved with the 75-variant panel in Black, Hispanic, and non-Hispanic White infants and with the 402-variant panel in Black, Hispanic, non-Hispanic White, and other race infants.
Larger CFTR panels in NBS improved the detection of CF in all races and ethnicities.
美国普遍开展新生儿囊性纤维化（CF）筛查（NBS）。方案有所不同，但包括免疫反应性胰蛋白酶原（IRT）水平和 CFTR 变异体检测。加利福尼亚州 CF NBS 有三步筛查：IRT 水平、变异体检测，如果仅在检测中发现一种变异体，则进行 CFTR 测序。
本研究为加利福尼亚州出生的 CF 患儿的队列研究，旨在研究 CF NBS 假阴性结果的种族和民族差异，以及假阴性发生在哪一步。我们研究了不同的 CFTR 变异体检测面板如何通过种族和民族提高对变异体的检测：原始的 39 个变异体检测面板、当前的 75 个变异体检测面板和 CFTR2 数据库中的所有 402 个致病 CFTR 变异体。
在加利福尼亚州出生的 912 名 CF 患儿中，有 84 名患儿出现 NBS 假阴性结果：38 名患儿因 IRT 水平低，46 名患儿因 IRT 值高（但不完全检测到变异体）。亚洲（OR6.3）和黑人（OR2.5）患儿发生 NBS 假阴性筛查结果的可能性高于非西班牙裔白人患儿。美国印第安人/阿拉斯加原住民和非西班牙裔白人患儿的假阴性筛查（而非 CF 诊断）病例主要归因于低 IRT 水平。大多数亚洲和西班牙裔患儿的 NBS 假阴性筛查结果未检测到变异体。在黑人、西班牙裔和非西班牙裔白人群体中，75 个变异体检测面板提高了对 CFTR 两种变异体的检测，在黑人、西班牙裔、非西班牙裔白人和其他种族群体中，402 个变异体检测面板提高了对 CFTR 两种变异体的检测。
NBS 中更大的 CFTR 检测面板提高了所有种族和民族的 CF 检测率。
