Tim G J de Meij1, Marc P C van der Schee2, Daan J C Berkhout1, Mirjam E van de Velde1, Anna E Jansen1, Boris W Kramer3, Mirjam M van Weissenbruch4, Anton H van Kaam5, Peter Andriessen6, Johannes B van Goudoever4, Hendrik J Niemarkt7, Nanne K H de Boer8. 1. Department of Pediatric Gastroenterology, Vrije Universiteit University Medical Center, Amsterdam, The Netherlands. 2. Department of Pediatric Pulmonology, Academic Medical Center, Amsterdam, The Netherlands. 3. Department of Pediatrics, Maastricht University Medical Center, Maastricht, The Netherlands. 4. Neonatal Intensive Care Unit, Vrije Universiteit University Medical Center, Amsterdam, The Netherlands. 5. Neonatal Intensive Care Unit, Academic Medical Center, Amsterdam, The Netherlands. 6. Department of Pediatrics, Maastricht University Medical Center, Maastricht, The Netherlands; Neonatal Intensive Care Unit, Máxima Medical Center, Veldhoven, The Netherlands. 7. Department of Pediatrics, Maastricht University Medical Center, Maastricht, The Netherlands. Electronic address: hendrik.niemarkt@mumc.nl. 8. Department of Gastroenterology and Hepatology, Vrije Universiteit University Medical Center, Amsterdam, The Netherlands.
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-1,0 (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.
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-1,0 (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.
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