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

64 Citations (Scopus)


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
Issue number3
Publication statusPublished - Sept 2015
Externally publishedYes


  • 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


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