Faecal volatile organic compounds in preterm babies at risk of necrotising enterocolitis: the DOVE study (original) (raw)
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Early Detection of Necrotizing Enterocolitis by Fecal Volatile Organic Compounds Analysis
The Journal of pediatrics, 2015
To test the hypothesis that fecal volatile organic compounds (VOCs) analysis by electronic nose (eNose) allows for early detection of necrotizing enterocolitis (NEC). 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. 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) ...
Fecal Volatile Organic Compounds in Preterm Infants Are Influenced by Enteral Feeding Composition
Sensors, 2018
Fecal volatile organic compound (VOC) analysis has shown great potential as a noninvasive diagnostic biomarker for a variety of diseases. Before clinical implementation, the factors influencing the outcome of VOC analysis need to be assessed. Recent studies found that the sampling conditions can influence the outcome of VOC analysis. However, the dietary influences remains unknown, especially in (preterm) infants. Therefore, we assessed the effects of feeding composition on fecal VOC patterns of preterm infants (born at <30 weeks gestation). Two subgroups were defined: (1) daily intake >75% breastmilk (BM) feeding and (2) daily intake >75% formula milk (FM) feeding. Fecal samples, which were collected at 7, 14 and 21 days postnatally, were analyzed by an electronic nose device (Cyranose 320®). In total, 30 preterm infants were included (15 FM, 15 BM). No differences in the fecal VOC patterns were observed at the three predefined time-points. Combining the fecal VOC profiles...
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2018
The intestinal microbiota has increasingly been considered to play a role in the etiology of late-onset sepsis (LOS). We hypothesize that early alterations in fecal volatile organic compounds (VOCs), reflecting intestinal microbiota composition and function, allow for discrimination between infants developing LOS and controls in a preclinical stage. In 9 neonatal intensive care units in the Netherlands and Belgium, fecal samples of preterm infants born at a gestational age ≤30 weeks were collected daily, up to the postnatal age of 28 days. Fecal VOC were measured by high-field asymmetric waveform ion mobility spectrometry (FAIMS). VOC profiles of LOS infants, up to 3 days prior to clinical LOS onset, were compared with profiles from matched controls. In total, 843 preterm born infants (gestational age ≤30 weeks) were included. From 127 LOS cases and 127 matched controls, fecal samples were analyzed by means of FAIMS. Fecal VOCs allowed for preclinical discrimination between LOS and ...
Microorganisms
Early detection of late-onset sepsis (LOS) in preterm infants is crucial since timely treatment initiation is a key prognostic factor. We hypothesized that fecal volatile organic compounds (VOCs), reflecting microbiota composition and function, could serve as a non-invasive biomarker for preclinical pathogen-specific LOS detection. Fecal samples and clinical data of all preterm infants (≤30 weeks’ gestation) admitted at nine neonatal intensive care units in the Netherlands and Belgium were collected daily. Samples from one to three days before LOS onset were analyzed by gas chromatography—ion mobility spectrometry (GC-IMS), a technique based on pattern recognition, and gas chromatography—time of flight—mass spectrometry (GC-TOF-MS), to identify unique metabolites. Fecal VOC profiles and metabolites from infants with LOS were compared with matched controls. Samples from 121 LOS infants and 121 matched controls were analyzed using GC-IMS, and from 34 LOS infants and 34 matched control...
Biosensors
Fecal volatile organic compounds (VOC) reflect human and gut microbiota metabolic pathways and their interaction. VOC behold potential as non-invasive preclinical diagnostic biomarkers in various diseases, e.g., necrotizing enterocolitis and late onset sepsis. There is a need for standardization and assessment of the influence of clinical and environmental factors on the VOC outcome before this technique can be applied in clinical practice. The aim of this study was to investigate the influence of gestational age (GA) and mode of delivery on the fecal VOC pattern in preterm infants born below 30 weeks of gestation. Longitudinal fecal samples, collected on days 7, 14, and 21 postnatally, were analyzed by an electronic nose device (Cyranose 320®). In total, 58 preterm infants were included (29 infants born at GA 24–26 weeks vs. 29 at 27–29 completed weeks, 24 vaginally born vs. 34 via C-section). No differences were identified at any predefined time point in terms of GA and delivery m...
The metabolomics of necrotising enterocolitis in preterm babies: an exploratory study
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians, 2015
No single diagnostic investigation is currently available for necrotising enterocolitis (NEC). We implemented a novel, untargeted, exploratory study to determine whether metabolomics can reveal early biomarker(s) of NEC. The effect of gestational age on the metabolome was also investigated. Two serum samples were obtained from 12 preterm babies (born <30 weeks gestation) and eight term controls: sample "A" at ≤1 week of age and sample "B" once fully fed. Samples were subjected to gas chromatography-mass spectrometry. Metabolomic data was analysed by principal component analysis (PCA), univariate and network analysis. Sixteen metabolite features significantly differed when B samples were compared between preterm babies who subsequently developed NEC and preterm/term controls (p value <0.05). Of these seven metabolites were linked to up-regulation of IL-1β. Significant differences in 54 metabolite features (p value <0.05) were observed between preterm and ...
2015
Necrotizing enterocolitis (NEC) is an inflammatory disease of the intestine primarily affecting preterm infants. Currently, the diagnosis of NEC is based on a constellation of non-specific clinical symptoms and signs, radiologic findings, and laboratory data (Bell's staging criteria). However, a definitive diagnosis of NEC is difficult because of its similarity in presentation to other clinical conditions. Biomarkers measured in stool samples will better reflect inflammation and pathology specific to the intestine. Certain stool markers are able to identify inflammatory bowel disease in pediatric and …
An analysis of volatiles in the headspace of the faeces of neonates
Journal of breath research, 2008
A gas chromatography/mass spectrometry (GCMS) analysis of the headspace from the faeces of neonates was undertaken to record the volatiles associated with preterm babies on a neonatal unit. The compounds ethanol, acetone, 2-ethyl-1-hexanol, 3-methylbutanal, hexanal and 2,3-butanedione occurred with the highest frequency. The volatiles analysed were then compared to a previously published study of the volatiles from asymptomatic adult faeces. Fewer compounds were found in the neonatal faeces and virtually no sulfides were detected, in contrast to the adult samples where carbon disulfide, dimethyl disulfide and dimethyl sulfide were ubiquitous. In addition, 7 of the most abundant 15 volatile compounds were found to be aldehydes, while in contrast only 2, acetaldehyde and benzaldehyde, were present in the most abundant 15 compounds found in the headspace of adult faeces. 2-Ethyl-1-hexanol was considerably more abundant in the neonate stool compared to adult stool, and probably reflects...
Biomarkers for Infants at Risk for Necrotizing Enterocolitis: Clues to Prevention?
Pediatric Research, 2009
Necrotizing enterocolitis (NEC) is the most common severe gastrointestinal emergency that affects premature newborns. This disease often has a rapid onset with few, if any, antecedent signs that can be used to reliably predict its occurrence. Its rapid onset and progression to death, as well as its severe morbidity when the infant survives, begs for early diagnostic tools that may be used in determining those infants who would be at greatest risk for development of the disease and for whom early preventative measures could be targeted. Although studies have suggested efficacy of several techniques such as breath hydrogen, inflammatory mediators in blood, urine or stool, and genetic markers, these all have drawbacks limiting their use. The application of newly developed "omic" approaches may provide biomarkers for early diagnosis and targeted prevention of this disease.
2013
Background: Necrotizing enterocolitis (NEC) is a devastating intestinal disease that afflicts 10% of extremely preterm infants. The contribution of early intestinal colonization to NEC onset is not understood, and predictive biomarkers to guide prevention are lacking. We analyzed banked stool and urine samples collected prior to disease onset from infants <29 weeks gestational age, including 11 infants who developed NEC and 21 matched controls who survived free of NEC. Stool bacterial communities were profiled by 16S rRNA gene sequencing. Urinary metabolomic profiles were assessed by NMR.