Diagnostic utility of rapid sequencing in critically ill infants: a systematic review and meta-analysis

Genetic disorders are a major cause of death in critically ill infants. Several studies have assessed the diagnostic yield of rapid genomic sequencing in critically ill infants. This meta-analysis aimed to summarize the diagnostic utility of rapid genomic sequencing in critically ill infants. PubMed, Scopus, Web of Science, and Cochrane Library, were searched before 1 July 2022. Studies reported diagnostic rate of rapid genomic sequencing in critically ill infants were selected. Two authors screened and extracted data regarding the method of genetic test, total number of patients, and number of diagnosed patients. Twenty-three studies, comprising 1567 critically ill infants were included in the meta-analysis. In the overall analysis, the pooled diagnostic utility of rapid genomic sequencing was 0.42 (95% CI: 0.37–0.49, I² = 79%, <i>P</i> &lt; 0.1). Moreover, the pooled diagnostic rates of rapid whole-exome and rapid whole-genome sequencing were 0.50 (95% CI: 0.41–0.61; I² = 74%; P &lt; 0.01) and 0.37 (95% CI: 0.30–0.46; I² = 77%; P &lt; 0.01), respectively. Sensitive analysis showed that the results were stable in the overall analysis. Additionally, publication bias was not observed in the overall analysis. This meta-analysis proved that rapid genomic sequencing has a good diagnostic utility for critically ill infants.遗传疾病是重症监护婴儿死亡的主要诱因。目前已有多项研究评估了快速基因组测序（rapid genomic sequencing）在重症监护婴儿中的诊断效能。本荟萃分析（meta-analysis）旨在总结快速基因组测序在该人群中的诊断应用价值。本研究于2022年7月1日前检索了PubMed、Scopus、Web of Science及Cochrane Library数据库，筛选纳入报道重症监护婴儿快速基因组测序诊断率的相关研究。由两名研究者独立完成文献筛选与数据提取，提取内容涵盖基因检测方法、患者总例数及确诊患者例数。最终共有23项符合标准的研究被纳入本次荟萃分析，累计涉及1567例重症监护婴儿。整体合并分析结果显示，快速基因组测序的合并诊断效能为0.42（95%置信区间（Confidence Interval, CI）：0.37~0.49，异质性指数I²=79%，P<0.1）。其中，快速全外显子测序（rapid whole-exome sequencing）与快速全基因组测序（rapid whole-genome sequencing）的合并诊断率分别为0.50（95%置信区间：0.41~0.61；I²=74%；P<0.01）与0.37（95%置信区间：0.30~0.46；I²=77%；P<0.01）。敏感性分析结果表明，整体分析的结论具有良好稳定性。此外，整体分析未观察到显著的发表偏倚。本荟萃分析证实，快速基因组测序对重症监护婴儿具备良好的诊断应用价值。