Bick Sarah L, Nathan Aparna, Park Hannah, Green Robert C, Wojcik Monica H, Gold Nina B
Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA; Division of Medical Genetics and Metabolism, Massachusetts General Hospital for Children, Boston, MA; Harvard Medical School, Boston, MA.
Department of Biomedical Informatics, Harvard Medical School, Boston, MA.
Genet Med. 2025 Jan;27(1):101284. doi: 10.1016/j.gim.2024.101284. Epub 2024 Sep 28.
Over 30 research groups and companies are exploring newborn screening using genomic sequencing (NBSeq), but the sensitivity of this approach is not well understood.
We identified individuals with treatable inherited metabolic disorders (IMDs) and ascertained the proportion whose DNA analysis revealed explanatory deleterious variants (EDVs). We examined variables associated with EDV detection and estimated the sensitivity of DNA-first NBSeq. We further predicted the annual rate of true-positive and false-negative NBSeq results in the United States for several conditions on the Recommended Uniform Screening Panel.
We identified 635 individuals with 80 unique IMDs. In univariate analyses, Black race (OR = 0.37, 95% CI: 0.16-0.89, P = .02) and public insurance (OR = 0.60, 95% CI: 0.39-0.91, P = .02) were less likely to be associated with finding EDVs. Had all individuals been screened with NBSeq, the sensitivity would have been 80.3%. We estimated that between 0 and 649.9 cases of Recommended Uniform Screening Panel IMDs would be missed annually by NBSeq in the United States.
The overall sensitivity of NBSeq for treatable IMDs is estimated at 80.3%. That sensitivity will likely be lower for Black infants and those who are on public insurance.
超过30个研究小组和公司正在探索使用基因组测序进行新生儿筛查（NBSeq），但这种方法的敏感性尚未得到充分了解。
我们确定了患有可治疗的遗传性代谢疾病（IMD）的个体，并确定了其DNA分析显示解释性有害变异（EDV）的比例。我们检查了与EDV检测相关的变量，并估计了DNA优先NBSeq的敏感性。我们进一步预测了美国在推荐统一筛查小组中几种疾病的NBSeq真阳性和假阴性结果的年发生率。
我们确定了635名患有80种独特IMD的个体。在单变量分析中，黑人种族（OR = 0.37，95% CI：0.16 - 0.89，P = 0.02）和公共保险（OR = 0.60，95% CI：0.39 - 0.91，P = 0.02）与发现EDV的关联较小。如果所有个体都接受NBSeq筛查，敏感性将为80.3%。我们估计，在美国，NBSeq每年将漏诊0至649.9例推荐统一筛查小组中的IMD病例。
NBSeq对可治疗的IMD的总体敏感性估计为80.3%。对于黑人婴儿和参加公共保险的婴儿，这种敏感性可能会更低。
