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

Chris Probert; Rosemary Greenwood; Arno Mayor; David Hughes; Raphael  Aggio; Rachel Elizabeth Jackson; Liz Simcox; Heather Barrow; Marta García-Finana; Andrew Ewer

doi:10.1136/archdischild-2019-318221

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

Chris Probert, Rosemary Greenwood, Arno Mayor, David Hughes, Raphael Aggio, Rachel Elizabeth Jackson, Liz Simcox, Heather Barrow, Marta García-Finana, Andrew Ewer

Metabolism and Systems Research

Research output: Contribution to journal › Article › peer-review

5 Citations (Scopus)

305 Downloads (Pure)

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.

Original language	English
Pages (from-to)	F1-F6
Number of pages	6
Journal	Archives of disease in childhood. Fetal and neonatal edition
Early online date	23 Dec 2019
DOIs	https://doi.org/10.1136/archdischild-2019-318221
Publication status	E-pub ahead of print - 23 Dec 2019

Keywords

necrotising enterocolitis
preterm infants
volatile organic compounds
longitudinal discriminant analysis

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10.1136/archdischild-2019-318221Licence: None: All rights reserved

Probert_et_al_Faecal_volatile_organic_compounds_in_preterm_babies_ADC_Fetal_&_Neonatal_edition_2019
This article has been accepted for publication in Archives of Disease in Childhood - Fetal and Neonatal Edition, 2019, following peer review, and the Version of Record can be accessed online at http://dx.doi.org/10.1136/archdischild-2019-318221
Accepted author manuscript, 793 KBLicence: None: All rights reserved

https://fn.bmj.com/content/early/2019/12/22/archdischild-2019-318221Licence: None: All rights reserved

Cite this

Probert, C., Greenwood, R., Mayor, A., Hughes, D., Aggio, R., Jackson, R. E., Simcox, L., Barrow, H., García-Finana, M., & Ewer, A. (2019). Faecal volatile organic compounds in preterm babies at risk of necrotising enterocolitis: the DOVE study. Archives of disease in childhood. Fetal and neonatal edition, F1-F6. Advance online publication. https://doi.org/10.1136/archdischild-2019-318221

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title = "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.",

keywords = "necrotising enterocolitis, preterm infants, volatile organic compounds, longitudinal discriminant analysis",

author = "Chris Probert and Rosemary Greenwood and Arno Mayor and David Hughes and Raphael Aggio and Jackson, {Rachel Elizabeth} and Liz Simcox and Heather Barrow and Marta Garc{\'i}a-Finana and Andrew Ewer",

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T1 - Faecal volatile organic compounds in preterm babies at risk of necrotising enterocolitis

T2 - the DOVE study

AU - Probert, Chris

AU - Greenwood, Rosemary

AU - Mayor, Arno

AU - Hughes, David

AU - Aggio, Raphael

AU - Jackson, Rachel Elizabeth

AU - Simcox, Liz

AU - Barrow, Heather

AU - García-Finana, Marta

AU - Ewer, Andrew

PY - 2019/12/23

Y1 - 2019/12/23

N2 - 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.

AB - 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.

KW - necrotising enterocolitis

KW - preterm infants

KW - volatile organic compounds

KW - longitudinal discriminant analysis

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U2 - 10.1136/archdischild-2019-318221

DO - 10.1136/archdischild-2019-318221

M3 - Article

SN - 1359-2998

SP - F1-F6

JO - Archives of disease in childhood. Fetal and neonatal edition

JF - Archives of disease in childhood. Fetal and neonatal edition

ER -

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

Abstract

Keywords

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