Early detection of necrotizing enterocolitis by fecal volatile organic compounds analysis

Tim G.J. de Meij, Marc P.C. van der Schee, Daan J.C. Berkhout, Mirjam E. van de Velde, Anna E. Jansen, Boris W. Kramer, Mirjam M. van Weissenbruch, Anton H. van Kaam, Peter Andriessen, Johannes B. van Goudoever, Hendrik J. Niemarkt, Nanne K.H. de Boer

Research output: Contribution to journalArticleAcademicpeer-review

27 Citations (Scopus)

Abstract

Objectives To test the hypothesis that fecal volatile organic compounds (VOCs) analysis by electronic nose (eNose) allows for early detection of necrotizing enterocolitis (NEC). Study design In 3 neonatal intensive care units, fecal samples of infants born at gestational age ≤30 weeks were collected daily, up to the 28th day of life. Included infants were allocated in 3 subgroups: NEC, sepsis, and matched controls. Three time windows were defined: (1) T-5,-4 (5 and 4 days before diagnosis); (2) T-3,-2 (3 and 2 days before diagnosis); and (3) T-1,-0 (day before and day of diagnosis). Three subgroups were analyzed by eNose. Results Fecal VOC profiles of infants with NEC (n = 13) could significantly be discriminated from matched controls (n = 14) at T-3,-2 (area under the curve ± 95% CI, P value, sensitivity, specificity: 0.77 ± 0.21, P =.02, 83%, 75%); the accuracy increased at T-3,-2 (0.99 ± 0.04, P ≤.001, 89%, 89%). VOC profiles of infants with NEC were also significantly different from those with sepsis (n = 31) at T-3,-2 (0.80 ± 0.17, P =.004, 83%, 75%), but not at T-1,0 (0.64 ± 0.18, P =.216, 89%, 57%). Conclusions In this proof of principle study, we observed that fecal VOC profiles of infants with NEC could be discriminated from controls, from 2-3 days predating onset of clinical symptoms. Our observations suggest that VOC-profiling by eNose has potential as a noninvasive tool for the early prediction of NEC.

Original languageEnglish
Pages (from-to)562-567
JournalJournal of Pediatrics
Volume167
Issue number3
DOIs
Publication statusPublished - Sep 2015
Externally publishedYes

Fingerprint

Volatile Organic Compounds
Necrotizing Enterocolitis
Electronic Nose
Sepsis
Neonatal Intensive Care Units
Gestational Age
Area Under Curve
Sensitivity and Specificity

Keywords

  • Early Diagnosis
  • Enterocolitis, Necrotizing/diagnosis
  • Feces/chemistry
  • Female
  • Humans
  • Infant, Newborn
  • Intensive Care Units, Neonatal
  • Male
  • Netherlands
  • Prospective Studies
  • ROC Curve
  • Sensitivity and Specificity
  • Sepsis/diagnosis
  • Time Factors
  • Volatile Organic Compounds/analysis

Cite this

de Meij, T. G. J., van der Schee, M. P. C., Berkhout, D. J. C., van de Velde, M. E., Jansen, A. E., Kramer, B. W., ... de Boer, N. K. H. (2015). Early detection of necrotizing enterocolitis by fecal volatile organic compounds analysis. Journal of Pediatrics, 167(3), 562-567. https://doi.org/10.1016/j.jpeds.2015.05.044
de Meij, Tim G.J. ; van der Schee, Marc P.C. ; Berkhout, Daan J.C. ; van de Velde, Mirjam E. ; Jansen, Anna E. ; Kramer, Boris W. ; van Weissenbruch, Mirjam M. ; van Kaam, Anton H. ; Andriessen, Peter ; van Goudoever, Johannes B. ; Niemarkt, Hendrik J. ; de Boer, Nanne K.H. / Early detection of necrotizing enterocolitis by fecal volatile organic compounds analysis. In: Journal of Pediatrics. 2015 ; Vol. 167, No. 3. pp. 562-567.
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title = "Early detection of necrotizing enterocolitis by fecal volatile organic compounds analysis",
abstract = "Objectives To test the hypothesis that fecal volatile organic compounds (VOCs) analysis by electronic nose (eNose) allows for early detection of necrotizing enterocolitis (NEC). Study design In 3 neonatal intensive care units, fecal samples of infants born at gestational age ≤30 weeks were collected daily, up to the 28th day of life. Included infants were allocated in 3 subgroups: NEC, sepsis, and matched controls. Three time windows were defined: (1) T-5,-4 (5 and 4 days before diagnosis); (2) T-3,-2 (3 and 2 days before diagnosis); and (3) T-1,-0 (day before and day of diagnosis). Three subgroups were analyzed by eNose. Results Fecal VOC profiles of infants with NEC (n = 13) could significantly be discriminated from matched controls (n = 14) at T-3,-2 (area under the curve ± 95{\%} CI, P value, sensitivity, specificity: 0.77 ± 0.21, P =.02, 83{\%}, 75{\%}); the accuracy increased at T-3,-2 (0.99 ± 0.04, P ≤.001, 89{\%}, 89{\%}). VOC profiles of infants with NEC were also significantly different from those with sepsis (n = 31) at T-3,-2 (0.80 ± 0.17, P =.004, 83{\%}, 75{\%}), but not at T-1,0 (0.64 ± 0.18, P =.216, 89{\%}, 57{\%}). Conclusions In this proof of principle study, we observed that fecal VOC profiles of infants with NEC could be discriminated from controls, from 2-3 days predating onset of clinical symptoms. Our observations suggest that VOC-profiling by eNose has potential as a noninvasive tool for the early prediction of NEC.",
keywords = "Early Diagnosis, Enterocolitis, Necrotizing/diagnosis, Feces/chemistry, Female, Humans, Infant, Newborn, Intensive Care Units, Neonatal, Male, Netherlands, Prospective Studies, ROC Curve, Sensitivity and Specificity, Sepsis/diagnosis, Time Factors, Volatile Organic Compounds/analysis",
author = "{de Meij}, {Tim G.J.} and {van der Schee}, {Marc P.C.} and Berkhout, {Daan J.C.} and {van de Velde}, {Mirjam E.} and Jansen, {Anna E.} and Kramer, {Boris W.} and {van Weissenbruch}, {Mirjam M.} and {van Kaam}, {Anton H.} and Peter Andriessen and {van Goudoever}, {Johannes B.} and Niemarkt, {Hendrik J.} and {de Boer}, {Nanne K.H.}",
note = "Copyright {\circledC} 2015 Elsevier Inc. All rights reserved.",
year = "2015",
month = "9",
doi = "10.1016/j.jpeds.2015.05.044",
language = "English",
volume = "167",
pages = "562--567",
journal = "Journal of Pediatrics",
issn = "0022-3476",
publisher = "Mosby Inc.",
number = "3",

}

de Meij, TGJ, van der Schee, MPC, Berkhout, DJC, van de Velde, ME, Jansen, AE, Kramer, BW, van Weissenbruch, MM, van Kaam, AH, Andriessen, P, van Goudoever, JB, Niemarkt, HJ & de Boer, NKH 2015, 'Early detection of necrotizing enterocolitis by fecal volatile organic compounds analysis', Journal of Pediatrics, vol. 167, no. 3, pp. 562-567. https://doi.org/10.1016/j.jpeds.2015.05.044

Early detection of necrotizing enterocolitis by fecal volatile organic compounds analysis. / de Meij, Tim G.J.; van der Schee, Marc P.C.; Berkhout, Daan J.C.; van de Velde, Mirjam E.; Jansen, Anna E.; Kramer, Boris W.; van Weissenbruch, Mirjam M.; van Kaam, Anton H.; Andriessen, Peter; van Goudoever, Johannes B.; Niemarkt, Hendrik J.; de Boer, Nanne K.H.

In: Journal of Pediatrics, Vol. 167, No. 3, 09.2015, p. 562-567.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Early detection of necrotizing enterocolitis by fecal volatile organic compounds analysis

AU - de Meij, Tim G.J.

AU - van der Schee, Marc P.C.

AU - Berkhout, Daan J.C.

AU - van de Velde, Mirjam E.

AU - Jansen, Anna E.

AU - Kramer, Boris W.

AU - van Weissenbruch, Mirjam M.

AU - van Kaam, Anton H.

AU - Andriessen, Peter

AU - van Goudoever, Johannes B.

AU - Niemarkt, Hendrik J.

AU - de Boer, Nanne K.H.

N1 - Copyright © 2015 Elsevier Inc. All rights reserved.

PY - 2015/9

Y1 - 2015/9

N2 - Objectives To test the hypothesis that fecal volatile organic compounds (VOCs) analysis by electronic nose (eNose) allows for early detection of necrotizing enterocolitis (NEC). Study design In 3 neonatal intensive care units, fecal samples of infants born at gestational age ≤30 weeks were collected daily, up to the 28th day of life. Included infants were allocated in 3 subgroups: NEC, sepsis, and matched controls. Three time windows were defined: (1) T-5,-4 (5 and 4 days before diagnosis); (2) T-3,-2 (3 and 2 days before diagnosis); and (3) T-1,-0 (day before and day of diagnosis). Three subgroups were analyzed by eNose. Results Fecal VOC profiles of infants with NEC (n = 13) could significantly be discriminated from matched controls (n = 14) at T-3,-2 (area under the curve ± 95% CI, P value, sensitivity, specificity: 0.77 ± 0.21, P =.02, 83%, 75%); the accuracy increased at T-3,-2 (0.99 ± 0.04, P ≤.001, 89%, 89%). VOC profiles of infants with NEC were also significantly different from those with sepsis (n = 31) at T-3,-2 (0.80 ± 0.17, P =.004, 83%, 75%), but not at T-1,0 (0.64 ± 0.18, P =.216, 89%, 57%). Conclusions In this proof of principle study, we observed that fecal VOC profiles of infants with NEC could be discriminated from controls, from 2-3 days predating onset of clinical symptoms. Our observations suggest that VOC-profiling by eNose has potential as a noninvasive tool for the early prediction of NEC.

AB - Objectives To test the hypothesis that fecal volatile organic compounds (VOCs) analysis by electronic nose (eNose) allows for early detection of necrotizing enterocolitis (NEC). Study design In 3 neonatal intensive care units, fecal samples of infants born at gestational age ≤30 weeks were collected daily, up to the 28th day of life. Included infants were allocated in 3 subgroups: NEC, sepsis, and matched controls. Three time windows were defined: (1) T-5,-4 (5 and 4 days before diagnosis); (2) T-3,-2 (3 and 2 days before diagnosis); and (3) T-1,-0 (day before and day of diagnosis). Three subgroups were analyzed by eNose. Results Fecal VOC profiles of infants with NEC (n = 13) could significantly be discriminated from matched controls (n = 14) at T-3,-2 (area under the curve ± 95% CI, P value, sensitivity, specificity: 0.77 ± 0.21, P =.02, 83%, 75%); the accuracy increased at T-3,-2 (0.99 ± 0.04, P ≤.001, 89%, 89%). VOC profiles of infants with NEC were also significantly different from those with sepsis (n = 31) at T-3,-2 (0.80 ± 0.17, P =.004, 83%, 75%), but not at T-1,0 (0.64 ± 0.18, P =.216, 89%, 57%). Conclusions In this proof of principle study, we observed that fecal VOC profiles of infants with NEC could be discriminated from controls, from 2-3 days predating onset of clinical symptoms. Our observations suggest that VOC-profiling by eNose has potential as a noninvasive tool for the early prediction of NEC.

KW - Early Diagnosis

KW - Enterocolitis, Necrotizing/diagnosis

KW - Feces/chemistry

KW - Female

KW - Humans

KW - Infant, Newborn

KW - Intensive Care Units, Neonatal

KW - Male

KW - Netherlands

KW - Prospective Studies

KW - ROC Curve

KW - Sensitivity and Specificity

KW - Sepsis/diagnosis

KW - Time Factors

KW - Volatile Organic Compounds/analysis

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U2 - 10.1016/j.jpeds.2015.05.044

DO - 10.1016/j.jpeds.2015.05.044

M3 - Article

C2 - 26188801

VL - 167

SP - 562

EP - 567

JO - Journal of Pediatrics

JF - Journal of Pediatrics

SN - 0022-3476

IS - 3

ER -

de Meij TGJ, van der Schee MPC, Berkhout DJC, van de Velde ME, Jansen AE, Kramer BW et al. Early detection of necrotizing enterocolitis by fecal volatile organic compounds analysis. Journal of Pediatrics. 2015 Sep;167(3):562-567. https://doi.org/10.1016/j.jpeds.2015.05.044