Predictive factors for surgical treatment in preterm neonates with necrotizing enterocolitis: a multicenter case-control study.

Necrotizing enterocolitis (NEC) is one of the most common and lethal gastrointestinal diseases in preterm infants. Early recognition of infants in need for surgical intervention might enable early intervention. In this multicenter case-control study, performed in nine neonatal intensive care units, preterm born infants (< 30 weeks of gestation) diagnosed with NEC (stage ≥ IIA) between October 2014 and August 2017 were divided into two groups: (1) medical (conservative treatment) and (2) surgical NEC (sNEC). Perinatal, clinical, and laboratory parameters were collected daily up to clinical onset of NEC. Univariate and multivariate logistic regression analyses were applied to identify potential predictors for sNEC. In total, 73 preterm infants with NEC (41 surgical and 32 medical NEC) were included. A low gestational age (p value, adjusted odds ratio [95%CI]; 0.001, 0.91 [0.86-0.96]), no maternal corticosteroid administration (0.025, 0.19 [0.04-0.82]), early onset of NEC (0.003, 0.85 [0.77-0.95]), low serum bicarbonate (0.009, 0.85 [0.76-0.96]), and a hemodynamically significant patent ductus arteriosus for which ibuprofen was administered (0.003, 7.60 [2.03-28.47]) were identified as independent risk factors for sNEC.Conclusions: Our findings may support the clinician to identify infants with increased risk for sNEC, which may facilitate early decisive management and consequently could result in improved prognosis. What is Known: • In 27-52% of the infants with NEC, a surgical intervention is indicated during its disease course. • Absolute indication for surgical intervention is bowel perforation, whereas fixed bowel loop or clinical deterioration highly suggestive of bowel perforation or necrosi, is a relative indication. What is New: • Lower gestational age, early clinical onset, and no maternal corticosteroids administration are predictors for surgical NEC. • Low serum bicarbonate in the 3 days prior clinical onset and patent ductus arteriosus for which ibuprofen was administered predict surgical NEC.

Optimized sample preparation for fecal volatile organic compound analysis by gas chromatography-mass spectrometry.

INTRODUCTION: Headspace gas chromatography-mass spectrometry (HS-GC-MS) is widely considered the gold standard of quantitative fecal VOC analysis. However, guidelines providing general recommendations for bioanalytical method application in research and clinical setting are lacking. OBJECTIVES: To propose an evidence-based research protocol for fecal VOC analysis by HS-GC-MS, based on extensive testing of instrumental and sampling conditions on detection and quantification limits, linearity, accuracy and repeatability of VOC outcome. METHODS: The influence of the following variables were assessed: addition of different salt solutions, injection temperature, injection speed, injection volume, septum use, use of calibration curves and fecal sample mass. Ultimately, the optimal sample preparation was assessed using fecal samples from healthy preterm infants. Fecal VOC analysis in this specific population has potential as diagnostic biomarkers, but available amount of feces is limited here, so optimization of VOC extraction is of importance. RESULTS: We demonstrated that addition of lithium chloride enhanced the release of polar compounds (e.g. small alcohols) into the headspace. Second, a linear relationship between injection volume, speed and temperature, and fecal sample mass on the abundance of VOC was demonstrated. Furthermore, the use of a septum preserved 90% of the non-polar compounds. By application of optimal instrumental and sampling conditions, a maximum of 320 unique compounds consisting of 14 different chemical classes could be detected. CONCLUSIONS: These findings may contribute to standardized analysis of fecal VOC by HS-GC-MS, facilitating future application of fecal VOC in clinical practice.

Development of severe bronchopulmonary dysplasia is associated with alterations in fecal volatile organic compounds.

BackgroundThe aim of this study was to evaluate the potential of fecal volatile organic compounds (VOCs), obtained by means of an electronic nose device (Cyranose 320), as early non-invasive biomarker for BPD.MethodsIn this nested case-control study performed at three Neonatal Intensive Care Units, fecal samples obtained at postnatal age of 7, 14, 21, and 28 days from preterm infants with severe bronchopulmonary dysplasia (BPD) were compared with fecal VOC profiles from matched controls. Microbiota analysis was performed by means of IS-pro technique on fecal samples collected at 28 days postnatally.ResultsVOC profiles of infants developing severe BPD (n=15) could be discriminated from matched controls (n=15) at postnatal age of 14 days (area under the curve (±95% confidence interval), P-value, sensitivity, specificity; 0.72 (0.54-0.90), 0.040, 60.0%, 73.3%), 21 days (0.71 (0.52-0.90), 0.049, 66.7%, 73.3%) and 28 days (0.77 (0.59-0.96), 0.017, 69.2%, 69.2%) but not at 7 days. Intestinal microbiota did not differ between BPD subjects and controls.ConclusionFecal VOC profiles of infants developing BPD could be differentiated from controls at postnatal day 14, 21, and 28. VOC differences could not be directed to intestinal microbiota alterations but presumably reflect local and systemic metabolic and inflammatory pathways associated with BPD.