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Faecal volatile organic compounds in preterm babies at risk of necrotising enterocolitis: the DOVE study
  1. Chris Probert1,
  2. Rosemary Greenwood2,
  3. Arno Mayor1,
  4. David Hughes3,
  5. Raphael Aggio1,
  6. Rachel Elizabeth Jackson4,
  7. Liz Simcox4,
  8. Heather Barrow4,
  9. Marta García-Finana3,
  10. Andrew K Ewer4,5
  1. 1Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK
  2. 2Department of Research and Innovation, University Hospitals Bristol NHS Foundation Trust, Bristol, UK
  3. 3Department of Biostatistics, Institute of Translation Medicine, University of Liverpool, Liverpool, UK
  4. 4Neonatal Unit, Birmingham Women’s and Children’s Hospital NHS Foundation Trust, Birmingham, UK
  5. 5Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, Universityof Birmingham, Birmingham, UK
  1. Correspondence to Professor Andrew K Ewer, Neonatal Unit, Birmingham Womens Hospital, Birmingham B15 2TG, UK; a.k.ewer{at}


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.

  • necrotising enterocolitis
  • preterm infants
  • volatile organic compounds
  • longitudinal discriminant analysis

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  • CP and RG are joint first authors.

  • Contributors CP and AKE: study concept and design; acquisition of data; analysis and interpretation of data; drafting of the manuscript; critical revision of the manuscript for important intellectual content; obtained funding; study supervision. RG, DH, MG-F: statistical analysis; analysis and interpretation of data; drafting of the manuscript; critical revision of the manuscript for important intellectual content; AM, RA: acquisition of data; analysis and interpretation of data; drafting of the manuscript; REJ, ES, HB: acquisition of data; drafting of the manuscript.

  • Funding This study was funded by The Henry Smith Charity and Action Medical Research. MG-F was supported by the UK EPSRC grant EP/N014499/1. DMH was supported by a UKRI Innovation Fellowship, funded by the MRC (Research Project MR/R024847/1).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval This study was sponsored by University of Birmingham and approved by West Midlands Research Ethics Committee (11/WM/0078).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available on reasonable request.