Department of Paediatrics and of Vaccine, Infection and Immunology, Spaarne Gasthuis Hospital, Haarlem, the Netherlands; Willem-Alexander Children's Hospital, Department of Pediatrics, Leiden University Medical Center, Leiden, the Netherlands.
Department of Paediatrics and of Vaccine, Infection and Immunology, Spaarne Gasthuis Hospital, Haarlem, the Netherlands.
Clin Microbiol Infect. 2024 Jul;30(7):850-857. doi: 10.1016/j.cmi.2024.03.005. Epub 2024 Mar 11.
An accurate diagnosis of early-onset sepsis (EOS) is challenging because of subtle symptoms and the lack of a good diagnostic tool, resulting in considerable antibiotic overtreatment. A biomarker, discriminating between infected and non-infected newborns at an early stage of the disease, could improve EOS prediction. Numerous biomarkers have been tested, but have never been compared directly.
We aimed to provide a comprehensive overview of early biomarkers and their diagnostic value in maternal samples, umbilical cord blood, and neonatal serum.
PubMed-Medline, EMBASE, The Cochrane Library, and Web of Science were searched up to 1 March 2023, without restrictions on publication date, population, or language.
Articles describing the diagnostic value of at least one biomarker in the detection of EOS in neonates, independent of gestational age, were included.
The QUADAS-2 tool was used to assess study quality.
Three independent researchers assessed the articles using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Meta-analysis was performed with all manuscripts describing diagnostic accuracy using a random-effects model.
Of 2296 identified articles, 171 reports were included in the systematic review and 69 in the meta-analysis. Literature showed mixed and inconsistent evidence for most biomarkers and sample types, because of a lack of a uniform EOS case definition, small sample sizes, and large heterogeneity between studies. Interesting markers were procalcitonin (pooled sensitivity 79%, 95% CI 71-84%; specificity 91%, 95% CI 83-96%, n = 11) and interleukin (IL)-6 (pooled sensitivity 83%, 95% CI 71-90%; specificity 87%, 95% CI 78-93%, n = 8) in umbilical cord blood and presepsin (pooled sensitivity 82%, 95% CI 62-93%; specificity 86%, 95% CI 73-93%, n = 3) and serum amyloid A (pooled sensitivity 92%, 95% CI 75-98%; specificity 96%, 95% CI 78-99%, n = 4) in neonatal serum. Studies on the combination of biomarkers were scarce.
A biomarker stand-alone test is currently not reliable for direct antibiotic stewardship in newborns, although several biomarkers show promising initial results. Further research into biomarker combinations could lead to an improved EOS diagnosis, reduce antibiotic overtreatment, and prevent associated health-related problems.
由于早期发病的症状不明显且缺乏良好的诊断工具，因此早期发病的脓毒症（EOS）的诊断具有挑战性，这导致了大量的抗生素过度治疗。一种能够在疾病早期区分感染和非感染新生儿的生物标志物，可以提高 EOS 的预测能力。已经测试了许多生物标志物，但从未直接进行过比较。
我们旨在全面概述母本样本、脐血和新生儿血清中早期生物标志物及其诊断价值。
截至 2023 年 3 月 1 日，在 PubMed-Medline、EMBASE、The Cochrane Library 和 Web of Science 上进行了检索，没有对出版物日期、人群或语言进行限制。
纳入了描述至少一种生物标志物在检测新生儿 EOS 中的诊断价值的文章，无论胎龄如何。
使用 QUADAS-2 工具评估研究质量。
三名独立研究人员使用系统评价和荟萃分析（PRISMA）指南对文章进行评估。使用随机效应模型对所有描述诊断准确性的手稿进行荟萃分析。
在 2296 篇确定的文章中，有 171 篇报告被纳入系统综述，69 篇报告被纳入荟萃分析。由于缺乏统一的 EOS 病例定义、样本量小以及研究之间存在很大的异质性，大多数生物标志物和样本类型的文献证据不一致。有趣的标志物有降钙素原（汇总敏感性 79%，95%CI 71-84%；特异性 91%，95%CI 83-96%，n=11）和白细胞介素（IL）-6（汇总敏感性 83%，95%CI 71-90%；特异性 87%，95%CI 78-93%，n=8）在脐血中，和前降钙素（汇总敏感性 82%，95%CI 62-93%；特异性 86%，95%CI 73-93%，n=3）和血清淀粉样蛋白 A（汇总敏感性 92%，95%CI 75-98%；特异性 96%，95%CI 78-99%，n=4）在新生儿血清中。关于生物标志物组合的研究很少。
目前，单独使用生物标志物并不可靠，无法直接用于新生儿的抗生素管理，尽管有几种生物标志物显示出有希望的初步结果。进一步研究生物标志物的组合可能会改善 EOS 的诊断，减少抗生素过度治疗，并预防相关的健康问题。
