Sensitivity of Dried Blood Spot Testing for Detection of Congenital Cytomegalovirus Infection.
Sensitivity of Dried Blood Spot Testing for Detection of Congenital Cytomegalovirus Infection.
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DOI：
10.1001/jamapediatrics.2020.5441
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发表时间：
2021-03-01
期刊：
影响因子：
26.1
通讯作者：
Schleiss MR
中科院分区：
文献类型：
--
作者：
Dollard SC;Dreon M;Hernandez-Alvarado N;Amin MM;Wong P;Lanzieri TM;Osterholm EA;Sidebottom A;Rosendahl S;McCann MT;Schleiss MR
本队列研究以唾液作为筛查参考标准，收集尿样确认先天性感染，评估干血斑聚合酶链反应筛查新生儿先天性巨细胞病毒感染的敏感性，采用目前最佳方法对用于新生儿普遍筛查的干血斑部署先天性巨细胞病毒进行聚合酶链反应检测的敏感性是什么？这项队列研究在明尼苏达州的一项多地点研究中筛选了12554名新生儿，其中56名（每1000人中有4.5人）确诊先天性巨细胞病毒感染。干血斑聚合酶链反应检测的敏感性为85.7%，2个实验室结果合并，明显高于以往研究报道。在本研究的中期分析中，干血斑相对较高的敏感性表明，随着DNA提取和聚合酶链反应方法的不断改进，它们可能用于通用巨细胞病毒筛查。干血斑（DBS）识别新生儿先天性巨细胞病毒（cCMV）感染的敏感性尚未在使用当前高灵敏度DBS处理方法的筛选研究中进行评估。目的评估DBS聚合酶链反应（PCR）筛查新生儿cCMV感染的敏感性，以唾液作为筛查参考标准，然后采集尿样确认先天性感染。这项基于人群的队列研究于2016年4月至2019年6月在明尼苏达州明尼阿波利斯/圣保罗地区的5个新生儿托儿所和3个新生儿重症监护病房进行。经父母同意入组的新生儿使用DBS进行常规新生儿筛查，并在出生后1至2天收集唾液进行cCMV筛查。在明尼苏达大学（UMN）和美国疾病控制与预防中心（CDC）用PCR检测了干血点的巨细胞病毒DNA。唾液拭子仅在UMN实验室用巨细胞病毒DNA PCR检测。通过唾液或DBS筛查呈阳性的新生儿有由初级保健专业人员获得的诊断性尿液样本，并在出生后3周内通过PCR检测。分析开始于2019年7月。用PCR法检测唾液拭子的巨细胞病毒。尿检证实cCMV的儿童人数和通过DBS筛查CMV阳性的儿童比例。截至2019年6月，在纳入的12554名患者中（预计入组人数为2.5万人），56名新生儿被确认患有cCMV （4.5 / 1000 [95% CI, 3.3-5.7]）。UMN或CDC联合DBS结果的敏感性为85.7% (48 / 56;95% CI, 74.3%-92.6%)，特异性为100.0% (95% CI, 100.0%-100.0%)，阳性预测值（PPV）为98.0% (95% CI, 89.3%-99.6%)，阴性预测值（NPV）为99.9% （95% CI, 99.9%-100.0%）。UMN干血斑结果的敏感性为73.2% (95% CI, 60.4% ~ 83.0%)，特异性为100.0% (100.0% ~ 100.0%)，PPV为100.0% (95% CI, 91.4% ~ 100.0%)， NPV为99.9% （95% CI, 99.8% ~ 99.9%）。CDC干血斑检测结果的敏感性为76.8% (95% CI, 64.2% ~ 85.9%)，特异性为100.0% (95% CI, 100.0% ~ 100.0%)， PPV为97.7% (95% CI, 88.2% ~ 99.6%)， NPV为99.9% （95% CI, 99.8% ~ 99.9%）。唾液拭子结果的敏感性为92.9% (52 / 56;95% CI, 83.0%-97.2%)，特异性为99.9% (95% CI, 99.9%-100.0%)， PPV为86.7% (95% CI, 75.8%-93.1%)， NPV为100.0% （95% CI, 99.9%-100.0%）。与以往进行基于人群筛查的研究相比，本研究显示DBS的分析灵敏度相对较高。随着更灵敏的DNA提取和PCR方法的不断出现，基于dbs的检测作为一种潜在的低成本、高通量的cCMV筛查选择，应该继续进行研究。
This cohort study assesses the sensitivity of dried blood spots polymerase chain reaction for newborn screening for congenital cytomegalovirus infection using saliva as the reference standard for screening, followed by collection of a urine sample for confirmation of congenital infection What is the sensitivity of polymerase chain reaction testing for congenital cytomegalovirus deployed on dried blood spots obtained for universal newborn screening using current best methods? This cohort study of 12 554 newborns screened in a multisite study in Minnesota included 56 (4.5 per 1000) with confirmed congenital cytomegalovirus infection. The sensitivity of dried blood spots polymerase chain reaction testing was 85.7% with results of 2 laboratory results combined, which is substantially higher than reported in past studies. The relatively high sensitivity of dried blood spots in the interim analysis of this study suggests their potential usefulness for universal cytomegalovirus screening as DNA extraction and polymerase chain reaction methodologies continue to improve. The sensitivity of dried blood spots (DBS) to identify newborns with congenital cytomegalovirus (cCMV) infection has not been evaluated in screening studies using the current, higher-sensitivity methods for DBS processing. To assess the sensitivity of DBS polymerase chain reaction (PCR) for newborn screening for cCMV infection using saliva as the reference standard for screening, followed by collection of a urine sample for confirmation of congenital infection. This population-based cohort study took place at 5 newborn nurseries and 3 neonatal intensive care units in the Minneapolis/Saint Paul area in Minnesota from April 2016 to June 2019. Newborns enrolled with parental consent were screened for cCMV using DBS obtained for routine newborn screening and saliva collected 1 to 2 days after birth. Dried blood spots were tested for CMV DNA by PCR at both the University of Minnesota (UMN) and the US Centers for Disease Control and Prevention (CDC). Saliva swabs were tested by CMV DNA PCR at the UMN laboratory only. Newborns who screened positive by saliva or DBS had a diagnostic urine sample obtained by primary care professionals, tested by PCR within 3 weeks of birth. Analysis began July 2019. Detection of CMV from a saliva swab using a PCR assay. Number of children with urine-confirmed cCMV and the proportion of them who were CMV positive through DBS screening. Of 12 554 individuals enrolled through June 2019 (of 25 000 projected enrollment), 56 newborns were confirmed to have cCMV (4.5 per 1000 [95% CI, 3.3-5.7]). Combined DBS results from either UMN or CDC had a sensitivity of 85.7% (48 of 56; 95% CI, 74.3%-92.6%), specificity of 100.0% (95% CI, 100.0%-100.0%), positive predictive value (PPV) of 98.0% (95% CI, 89.3%-99.6%), and negative predictive value (NPV) of 99.9% (95% CI, 99.9%-100.0%). Dried blood spot results from UMN had a sensitivity of 73.2% (95% CI, 60.4%-83.0%), specificity of 100.0% (100.0%-100.0%), PPV of 100.0% (95% CI, 91.4%-100.0%), and NPV of 99.9% (95% CI, 99.8%-99.9%). Dried blood spot results from CDC had a sensitivity of 76.8% (95% CI, 64.2%-85.9%), specificity of 100.0% (95% CI, 100.0%-100.0%), PPV of 97.7% (95% CI, 88.2%-99.6%), and NPV of 99.9% (95% CI, 99.8%-99.9%). Saliva swab results had a sensitivity of 92.9% (52 of 56; 95% CI, 83.0%-97.2%), specificity of 99.9% (95% CI, 99.9%-100.0%), PPV of 86.7% (95% CI, 75.8%-93.1%), and NPV of 100.0% (95% CI, 99.9%-100.0%). This study demonstrates relatively high analytical sensitivity for DBS compared with previous studies that performed population-based screening. As more sensitive DNA extraction and PCR methods continue to emerge, DBS-based testing should remain under investigation as a potential low-cost, high-throughput option for cCMV screening.
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