Karl G Sylvester1, Xuefeng B Ling2, G Y Liu3, Zachary J Kastenberg2, Jun Ji2, Zhongkai Hu2, Sihua Peng2, Ken Lau2, Fizan Abdullah4, Mary L Brandt5, Richard A Ehrenkranz6, Mary Catherine Harris7, Timothy C Lee5, Joyce Simpson6, Corinna Bowers8, R Lawrence Moss8. 1. Division of Pediatric Surgery, Lucile Packard Children's Hospital, Stanford, USA Department of Surgery, Stanford University School of Medicine, Stanford, USA. 2. Department of Surgery, Stanford University School of Medicine, Stanford, USA. 3. Department of Surgery, Stanford University School of Medicine, Stanford, USA Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, USA. 4. Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, USA. 5. Department of Surgery, Texas Children's Hospital, Baylor College of Medicine, Houston, USA. 6. Department of Pediatrics, Yale University School of Medicine, New Haven, USA. 7. Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, USA. 8. Division of Pediatric Surgery, Nationwide Children's Hospital, Columbus, USA Department of Surgery, Ohio State College of Medicine, Columbus, USA.
Abstract
OBJECTIVE:Necrotising enterocolitis (NEC) is a major source of neonatal morbidity and mortality. The management of infants with NEC is currently complicated by our inability to accurately identify those at risk for progression of disease prior to the development of irreversible intestinal necrosis. We hypothesised that integrated analysis of clinical parameters in combination with urine peptide biomarkers would lead to improved prognostic accuracy in the NEC population. DESIGN:Infants under suspicion of having NEC (n=550) were prospectively enrolled from a consortium consisting of eight university-based paediatric teaching hospitals. Twenty-seven clinical parameters were used to construct a multivariate predictor of NEC progression. Liquid chromatography/mass spectrometry was used to profile the urine peptidomes from a subset of this population (n=65) to discover novel biomarkers of NEC progression. An ensemble model for the prediction of disease progression was then created using clinical and biomarker data. RESULTS: The use of clinical parameters alone resulted in a receiver-operator characteristic curve with an area under the curve of 0.817 and left 40.1% of all patients in an 'indeterminate' risk group. Three validated urine peptide biomarkers (fibrinogen peptides: FGA1826, FGA1883 and FGA2659) produced a receiver-operator characteristic area under the curve of 0.856. The integration of clinical parameters with urine biomarkers in an ensemble model resulted in the correct prediction of NEC outcomes in all cases tested. CONCLUSIONS: Ensemble modelling combining clinical parameters with biomarker analysis dramatically improves our ability to identify the population at risk for developing progressive NEC. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
RCT Entities:
OBJECTIVE:Necrotising enterocolitis (NEC) is a major source of neonatal morbidity and mortality. The management of infants with NEC is currently complicated by our inability to accurately identify those at risk for progression of disease prior to the development of irreversible intestinal necrosis. We hypothesised that integrated analysis of clinical parameters in combination with urine peptide biomarkers would lead to improved prognostic accuracy in the NEC population. DESIGN:Infants under suspicion of having NEC (n=550) were prospectively enrolled from a consortium consisting of eight university-based paediatric teaching hospitals. Twenty-seven clinical parameters were used to construct a multivariate predictor of NEC progression. Liquid chromatography/mass spectrometry was used to profile the urine peptidomes from a subset of this population (n=65) to discover novel biomarkers of NEC progression. An ensemble model for the prediction of disease progression was then created using clinical and biomarker data. RESULTS: The use of clinical parameters alone resulted in a receiver-operator characteristic curve with an area under the curve of 0.817 and left 40.1% of all patients in an 'indeterminate' risk group. Three validated urine peptide biomarkers (fibrinogen peptides: FGA1826, FGA1883 and FGA2659) produced a receiver-operator characteristic area under the curve of 0.856. The integration of clinical parameters with urine biomarkers in an ensemble model resulted in the correct prediction of NEC outcomes in all cases tested. CONCLUSIONS: Ensemble modelling combining clinical parameters with biomarker analysis dramatically improves our ability to identify the population at risk for developing progressive NEC. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
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