Faecal volatile organic compounds in preterm babies at risk of necrotising enterocolitis: The DOVE study

Abstract

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 <34 weeks gestation. 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.