Faecal volatile organic compounds in preterm babies at risk of necrotising enterocolitis: the DOVE study
Faecal volatile organic compounds in preterm babies at risk of necrotising enterocolitis: the DOVE study
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DOI：
10.1136/archdischild-2019-318221
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发表时间：
2020-09-01
影响因子：
4.4
通讯作者：
Ewer, Andrew K.
中科院分区：
文献类型：
--
作者：
Probert, Chris;Greenwood, Rosemary;Ewer, Andrew K.
背景：坏死性小肠结肠炎(NEC)的早期诊断可能会改善预后，但尚无已证实的生物标志物。目的探讨粪便挥发性有机化合物(VOCs)作为NEC潜在生物标志物的变化。设计多中心前瞻性研究。设置8个英国新生儿单位。方法前瞻性采集1326例早产儿每日粪便标本，其中49例确诊为NEC。32例NEC患者的粪便样本与频率匹配的对照组样本进行了比较。顶空、固相微萃取、气相色谱/质谱联用，从参考文库中鉴定挥发性有机化合物。用判别分析和因子分析两种方法对病例和对照的挥发性有机化合物样本进行比较。结果VOCs可分为9组(因子)，其中3组与NEC相关，提示在临床确诊前3~4d有发病可能。其中一个因素是，每增加1个SD，患NEC的几率增加1.6倍；另外两个因素的相似降低与风险降低相关(OR分别为0.5或0.7)。判别分析确定了五个单独的VOCs，它们与高危婴儿的NEC有关，每个VOCs在接收器工作特征曲线下的面积为0.75-0.76，直到做出临床诊断的前4天。结论NEC早产儿粪便VOCs发生改变。目前，这些数据不足以可靠地检测出有患NEC风险的婴儿，还需要进一步研究VOCs在阐明NEC病因学中的作用。
Background Early diagnosis of necrotising enterocolitis (NEC) may improve prognosis but there are no proven biomarkers. Objective To investigate changes in faecal volatile organic compounds (VOCs) as potential biomarkers for NEC. Design Multicentre prospective study. Settings 8 UK neonatal units. Patients Preterm infants Methods Daily faecal samples were collected prospectively from 1326 babies of whom 49 subsequently developed definite NEC. Faecal samples from 32 NEC cases were compared with samples from frequency-matched controls without NEC. Headspace, solid phase microextraction gas chromatography/mass spectrometry was performed and VOCs identified from reference libraries. VOC samples from cases and controls were compared using both discriminant and factor analysis methods. Results VOCs were found to cluster into nine groups (factors), three were associated with NEC and indicated the possibility of disease up to 3-4 days before the clinical diagnosis was established. For one factor, a 1 SD increase increased the odds of developing NEC by 1.6 times; a similar decrease of the two other factors was associated with a reduced risk (OR 0.5 or 0.7, respectively). Discriminant analyses identified five individual VOCs, which are associated with NEC in babies at risk, each with an area under the receiver operating characteristics curve of 0.75-0.76, up to 4 days before the clinical diagnosis was made. Conclusions Faecal VOCs are altered in preterm infants with NEC. These data are currently insufficient to enable reliable cotside detection of babies at risk of developing NEC and further work is needed investigate the role of VOCs in clarifying the aetiology of NEC.