Near-Infrared Spectroscopy: A Tool for Diagnosing Necrotizing Enterocolitis at Onset of Symptoms in Preterm Neonates with Acute Gastrointestinal Symptoms?

OBJECTIVE: In premature neonates, bloody stools and/or abdominal distension with feeding intolerance may be inaugural signs of necrotizing enterocolitis (NEC). We assessed the ability of near-infrared spectroscopy (NIRS) to distinguish those neonates with NEC soon after the occurrence of these symptoms. STUDY DESIGN: We prospectively collected NIRS measurements of abdominal and cerebral regional tissue oxygen saturation (r-SO2), with values masked by an opaque cover. Two physicians, blinded to the NIRS data, determined whether the gastrointestinal symptoms were related to NEC 10 days after symptom onset. RESULTS: Forty-five neonates with mean (standard deviation [SD]) gestational, birth weight and postnatal ages of 31 (3.9) weeks, 1,486 (794) g, and 18 (14) days were enrolled over 30 months. Gastrointestinal symptoms were related to NEC in 23 patients and associated with other causes in 22. Analysis of the 48 hours of monitoring revealed comparable abdominal r-SO2 and splanchnic-cerebral oxygenation ratio (SCOR) in patients with and without NEC (r-SO2: 47.3 [20.4] vs. 50.4 [17.8], p = 0.59, SCOR: 0.64 [0.26] vs. 0.69 [0.24], p = 0.51). Results were unchanged after NIRS analysis in 6-hour periods, and restriction of the analysis to severe NEC (i.e., grade 2 and 3, 57% of the NEC cases). CONCLUSION: In this study, NIRS monitoring was unable to individualize NEC in premature infants with acute gastrointestinal symptoms.

A Nursing Survey on Nutritional Care Practices in French-Speaking Pediatric Intensive Care Units: NutriRéa-Ped 2014.

OBJECTIVES: Malnutrition in critically ill children contributes to morbidity and mortality. The French-speaking pediatric intensive care nutrition group (NutriSIP) aims to promote optimal nutrition through education and research. METHODS: The NutriSIP-designed NutriRéa-Ped study included a cross-sectional survey. This 62-item survey was sent to the nursing teams of all of the French-speaking pediatric intensive care units (PICUs) to evaluate nurses' nutrition knowledge and practices. One nurse per PICU was asked to answer and describe the practices of their team. RESULTS: Of 44 PICUs, 40 responded in Algeria, Belgium, Canada, France, Lebanon, Luxemburg, and Switzerland. The majority considered nutrition as a priority care but only 12 of the 40 (30%) had a nutrition support team, 26 of the 40 (65%) had written nutrition protocols, and 19 of 39 (49%) nursing teams felt confident with the nutrition goals. Nursing staff generally did not know how to determine nutritional requirements or to interpret malnutrition indices. They were also unaware of reduced preoperative fasting times and fast-track concepts. In 17 of 35 (49%) PICUs, the target start time for enteral feeding was within the first 24 hours; however, frequent interruptions occurred because of neuromuscular blockade, fasting for extubation or surgery, and high gastric residual volumes. Combined pediatric neonatal intensive care units were less likely to perform systematic nutritional assessment and to start enteral nutrition rapidly. CONCLUSIONS: We found a large variation in nursing practices around nutrition, exacerbated by the lack of nutritional guidelines but also because of the inadequate nursing knowledge around nutritional factors. These findings encourage the NutriSIP to improve nutrition through focused education programs and research.

Clostridium butyricum Strains and Dysbiosis Linked to Necrotizing Enterocolitis in Preterm Neonates.

BACKGROUND: Necrotizing enterocolitis (NEC) is the most common and serious gastrointestinal disorder among preterm neonates. We aimed to assess a specific gut microbiota profile associated with NEC. METHODS: Stool samples and clinical data were collected from 4 geographically independent neonatal intensive care units, over a 48-month period. Thirty stool samples from preterm neonates with NEC (n = 15) and controls (n = 15) were analyzed by 16S ribosomal RNA pyrosequencing and culture-based methods. The results led us to develop a specific quantitative polymerase chain reaction (qPCR) assay for Clostridium butyricum, and we tested stool samples from preterm neonates with NEC (n = 93) and controls (n = 270). We sequenced the whole genome of 16 C. butyricum strains, analyzed their phylogenetic relatedness, tested their culture supernatants for cytotoxic activity, and searched for secreted toxins. RESULTS: Clostridium butyricum was specifically associated with NEC using molecular and culture-based methods (15/15 vs 2/15; P < .0001) or qPCR (odds ratio, 45.4 [95% confidence interval, 26.2-78.6]; P < .0001). Culture supernatants of C. butyricum strains from preterm neonates with NEC (n = 14) exhibited significant cytotoxic activity (P = .008), and we identified in all a homologue of the ß-hemolysin toxin gene shared by Brachyspira hyodysenteriae, the etiologic agent of swine dysentery. The corresponding protein was secreted by a NEC-associated C. butyricum strain. CONCLUSIONS: NEC was associated with C. butyricum strains and dysbiosis with an oxidized, acid, and poorly diversified gut microbiota. Our findings highlight the plausible toxigenic mechanism involved in the pathogenesis of NEC.

Temporal dynamics of the very premature infant gut dominant microbiota.

BACKGROUND: The very-preterm infant gut microbiota is increasingly explored due to its probable role in the development of life threatening diseases. Results of high-throughput studies validate and renew the interest in approaches with lower resolution such as PCR-Temporal Temperature Gel Electrophoresis (TTGE) for the follow-up of dominant microbiota dynamics. We report here an extensive longitudinal study of gut colonization in very preterm infants. We explored by 16S rDNA-based PCR-TTGE a total of 354 stool specimens sampled during routine monitoring from the 1(st) to the 8(th) week of life in 30 very pre-term infants born before 30 weeks of gestational age. RESULTS: Combining comparison with a diversity ladder and sequencing allowed affiliation of 50 Species-Level Operational Taxonomic Units (SLOTUs) as well as semi-quantitative estimation of Operational Taxonomic Units (OTUs). Coagulase-negative staphylococci, mainly the Staphylococcus epidermidis, was found in all the infants during the study period and was the most represented (75.7% of the SLOTUs) from the first days of life. Enterococci, present in 60% of the infants were early, highly represented and persistent colonizers of the premature gut. Later Enterobacteriaceae and the genus Clostridium appeared and were found in 10 (33%) and 21 infants (70%), respectively. We showed a high representation of Veillonella in more than a quarter of the infants and being able to persistently colonize premature gut. The genera Anaerococcus, Aquabacterium, Bacillus, Bifidobacterium, Corynebacterium, Micrococcus, Oceanobacillus, Propionibacterium, Pseudomonas, Rothia, Sarcina, Sneathia and Streptococcus were observed as transient or persistent colonizers, each genus being found in a minority of infants. CONCLUSIONS: Despite low resolution, PCR-TTGE remains complementary to high-throughput sequencing-based approaches because it allows the follow-up of dominant bacteria in gut microbiota in a large longitudinal cohorts of preterm neonates. We described the development of pre-term gut microbiota that should be now replaced regarding the functional role of major OTUs.

Thoracic computed tomography in absent pulmonary valve syndrome management.

A neonate with absent pulmonary valve syndrome (APVS) and features of tetralogy of Fallot presented respiratory distress. The prolonged need for mechanical ventilation was an indication for surgical repair. Preoperative thoracic CT imaging showed nearly complete closure of the distal trachea, compressed by the aneurysmal dilatation of the pulmonary arteries, and its reopening after ventilator pressure was increased. Management of APVS may require high-pressure ventilation to prevent bronchial collapse due to compression by the pulmonary arteries. In this context, thoracic CT imaging is very useful for adjusting ventilation support so that surgical repair can be performed in optimal conditions.

Dynamics and clinical evolution of bacterial gut microflora in extremely premature patients.

OBJECTIVE: To determine baseline clinical characteristics that influence bacterial gut flora dynamics in very preterm infants and the relationship between gut flora dynamics and clinical evolution. STUDY DESIGN: Prospective, monocentric study enrolling 29 consecutive very preterm infants. We collected data about growth, digestive tolerance, nutrition, and antibiotic use. Microflora in stool samples, collected between 3 and 56 days of life, was identified with direct molecular fingerprinting. RESULTS: Median (interquartile range) body weight and gestational age at birth were 950 g (760-1060 g) and 27 weeks (27-29 weeks), respectively. The diversity score (number of operational taxonomic units) increased 0.45 units/week (P < .0001), with staphylococci as the major group. Bifidobacterium was poorly represented. Gestational age (≥ 28 weeks) and caesarean delivery independently correlated with better diversity scores during follow-up (P < .05). The 6-week diversity score inversely correlated with the duration of antibiotherapy (P = .0184) and parenteral feeding (P = .013). The microflora dynamics was associated with the digestive tolerance profile. Weight gain increased with increasing diversity score (P = .0428). CONCLUSION: Microflora diversity settled progressively in very preterm infants. Staphylococci were the major group, and few infants were colonized with Bifidobacterium spp. Measures that may improve microflora could have beneficial effects on digestive tolerance and growth.

NUTRI-REAPED study: nutritional assessment of French critically ill children and nutrition practice survey in French-speaking pediatric intensive care units.

BACKGROUND: Impaired nutritional status is adversely associated with suboptimal outcomes in critically ill children. Undernutrition at pediatric intensive care unit (PICU) admission ranges from 15 to 65%. A lack of knowledge of the nutritional status of children in French PICUs prevents us from specifically targeting education. This study aims to describe the nutritional status of children in French PICUs and to assess nutritional practices and physicians' knowledge of nutrition, in order to focus NutriSIP (the French-speaking PICU nutrition group) future education programs. A prospective observational multicenter point prevalence study was conducted in French PICUs, recruiting all children admitted over three different weeks. Anthropometric measurements were taken (weight, height/length, mid-upper arm, and head circumferences), in order to calculate nutritional indices. Nutritional status was defined according to WHO Body Mass Index z-score and dynamic assessment based on growth faltering detection. Concurrently, PICU physicians and PICU nurses from seven French-speaking countries completed a survey to ascertain knowledge about local nutritional care practices and overall nutrition knowledge. PICU physicians' responses were compared to PICU nurses' responses (previously published). RESULTS: Four hundred and thirty-two children were included in the observational study from 27 French PICUs. Undernutrition was diagnosed in 18.5% of them, young age and underlying chronic condition being the two independent risk factors. Faltering growth was diagnosed in 4.8% and overweight in 7.4%. Subjective nutritional assessment was not accurate. Thirty-eight French-speaking PICUs completed the survey. These showed nutritional practices frequently did not comply with international guidelines, especially regarding nutritional goals, and the reasons for withholding enteral nutrition. Comparison between physicians' and nurses' responses to the survey showed large discrepancies. CONCLUSION: Undernutrition is frequent at admission in French PICUs. Nutritional status should be assessed using a holistic approach, because of the potential impact on outcome. French-speaking PICU healthcare professionals need further nutrition education, in order to improve nutritional practices to comply with international recommendations. This study will serve as a baseline to focus NutriSIP teaching programs in the future.

Probiotics and growth in preterm infants: A randomized controlled trial, PREMAPRO study.

BACKGROUND & AIMS: Recent studies have suggested that the gut microflora has metabolic effects. We aimed to evaluate postnatal growth in preterm infants who received different probiotic supplements, and to assess the safety of probiotic administration. METHODS: This prospective, randomized, double-blind, controlled trial was performed at three tertiary care neonatal units. Preterm infants were randomly assigned to receive daily supplementation over 4-6 weeks with placebo (group C) or probiotics (group P). Group P comprised three subgroups: P1 received Bifidobacterium lactis, P2 received Bifidobacterium longum, and P3 received B. lactis and B. longum. We assessed postnatal growth during the supplementation period and up to a corrected gestational age (GA) of 41 weeks when body composition was assessed using whole-body dual-energy X-ray absorptiometry. Aerobic and anaerobic blood cultures were performed on suspicion of late-onset sepsis. RESULTS: The study comprised 199 preterm infants with a mean GA of 29.1 ± 1.4 weeks and a mean birth weight of 1173 ± 210 g, who received a placebo (group C, n = 52) or probiotics (group P, n = 147) from the first week of life. At the end of the supplementation period, no statistically significant differences were seen between the groups in relation to the mean body weight (group C = 1906 ± 23 g, group P = 1875 ± 14 g, p = 0.25), length, or head circumference. The incidence rates of necrotizing enterocolitis and late-onset sepsis were similar in the two groups. At the corrected GA of 41 weeks, there were no differences between the groups with respect to anthropometric measurements or body composition analysis. CONCLUSIONS: Preterm infants receiving Bifidobacterium supplements did not exhibit better postnatal growth compared with those who received placebo treatment. No adverse effects were associated with probiotic administration. Registered under ClinicalTrials.gov Identifier no. NCT01379417.

High-flow nasal cannula: recommendations for daily practice in pediatrics.

High-flow nasal cannula (HFNC) is a relatively new device for respiratory support. In pediatrics, HFNC use continues to increase as the system is easily set up and is well tolerated by patients. The use of nasal cannula adapted to the infant's nares size to deliver heated and humidified gas at high flow rates has been associated with improvements in washout of nasopharyngeal dead space, lung mucociliary clearance, and oxygen delivery compared with other oxygen delivery systems. HFNC may also create positive pharyngeal pressure to reduce the work of breathing, which positions the device midway between classical oxygen delivery systems, like the high-concentration face mask and continuous positive airway pressure (CPAP) generators. Currently, most of the studies in the pediatric literature suggest the benefits of HFNC therapy only for moderately severe acute viral bronchiolitis. But, the experience with this device in neonatology and adult intensive care may broaden the pediatric indications to include weaning from invasive ventilation and acute asthma. As for any form of respiratory support, HFNC initiation in patients requires close monitoring, whether it be for pre- or inter-hospital transport or in the emergency department or the pediatric intensive care unit.

tuf-PCR-temporal temperature gradient gel electrophoresis for molecular detection and identification of staphylococci: application to breast milk and neonate gut microbiota.

Coagulase negative staphylococci (CoNS) are a leading cause of infections in preterm infants, mostly involved in late-onset infection in low birth weight neonates. The epidemiology and pathophysiology of these infections remain unclear, notably because the causing agents are gathered in the artificial CoNS group. The aim of this work was to optimize the study of Staphylococcus species diversity in human breast milk and neonate stool, two sample types with bacterial communities dominated by CoNS, using PCR-temporal temperature gel electrophoresis based on the tuf gene. The optimized protocol identified 18 Staphylococcus species involved in neonate gut microbiota and infections and was applied to cultivation-independent study of breast milk and neonate stool. The efficiency, sensitivity, specificity and species discrimination of the proposed protocol appears suitable for patient follow-up in order to link microbiological data at the community level in milk and stool and interpret them from epidemiological and pathophysiological points of view.

6 cmH2O continuous positive airway pressure versus conventional oxygen therapy in severe viral bronchiolitis: a randomized trial.

OBJECTIVE: To compare the effects of nasal continuous positive airway pressure (nCPAP) and conventional oxygen therapy on the clinical signs of respiratory distress and the respiratory muscle workload in acute viral bronchiolitis. DESIGN: Prospective, randomized, monocentric study carried out in the pediatric intensive care unit (PICU) of a university hospital. PATIENTS: Infants <6 months old, admitted to the PICU with severe respiratory syncytial virus bronchiolitis. INTERVENTION: The patients were randomized into two groups for 6 hr. The nCPAP group (n = 10) received 6 cmH(2)O pressure support delivered by a jet flow generator and the control group (n = 9) received an air/oxygen mixture from a heated humidifier. Respiratory distress was assessed by the modified Wood's clinical asthma score (m-WCAS), and inspiratory muscle work was evaluated by calculating the pressure-time product per breath (PTP(insp) /breath) and per minute (PTP(insp) /min) from the esophageal pressure (Pes) recordings. MEASUREMENTS AND MAIN RESULTS: Compared with control condition, nCPAP decreased m-WCAS [-2.4 (1.05) vs. -0.5 (1.3), P = 0.03], PTPes(insp)/breath [-9.7 (5.7) vs. -1.4 (8.2), P = 0.04], PTPes(insp) /min [-666 (402) vs. -116 (352), P = 0.015], and FiO(2) [-7 (10) vs. +5 (15), P = 0.05]. Significant worsening of m-WCAS was only observed in the control group (4/9 vs. 0/10, P = 0.03). CONCLUSIONS: nCPAP rapidly decreased inspiratory work in young infants with acute bronchiolitis. Improvement in the respiratory distress score at 6 hr was proportional to the initial clinical severity, suggesting the importance of rapid nCPAP initiation in the more severe forms of the disease.

Validation of a neonatal pain scale adapted to the new practices in caring for preterm newborns.

UNLABELLED: BACKGROUND Neonatal pain assessment generally requires access to facial expression. Improved neonatology practices, such as greater protection against bright lights and non-invasive mask ventilation, have made facial observation more difficult. OBJECTIVE: To validate a 'faceless' acute neonatal pain scale (FANS), which does not depend on facial expression. METHODS: In a prospective, multicentre study, 24-40-week-old neonates were videotaped during a painful procedure (heel prick). Three investigators then scored the pain using FANS and a previously validated scale: DAN (Douleur aiguë du Nouveau-né). FANS is based on assessment of limb movement, cry and autonomic reaction. Reliability was assessed by inter-rater agreement and internal consistency (Cronbach's alpha). Validity was evaluated by agreement between scales (intraclass correlation coefficient (ICC)). The Wilcoxon test evaluated the FANS score differences between conditions. Results are expressed as medians (25th and 75th percentiles). Ranges are presented for outcome parameters. RESULTS: From April 2006 to September 2007, 53 preterms of 32 (30-35) gestational weeks and 1500 (1000-2200) g were observed. Cronbach's alpha was 0.72. The ICC was 0.92 (0.9-0.98) for inter-rater agreement and 0.88 (0.76-0.93) for agreement between scales. CONCLUSION: FANS, which is reliable and valid, is the first scale to score pain in preterm newborns when facial expression is not accessible.

Optimized PCR-Temporal Temperature Gel Electrophoresis compared to cultivation to assess diversity of gut microbiota in neonates.

Temporal Temperature Gel Electrophoresis of amplified 16S rRNA gene sequences (16S rDNA PCR-TTGE) constitutes a culture-independent molecular method used to study bacterial communities. All the technical steps are crucial for quality and exhaustiveness of the results obtained by such approach. Careful optimization of the protocols used is ideally needed for each ecosystem studied. We present here the strategy used to construct an optimized protocol for a 16S rDNA PCR-TTGE-based analysis of gut microflora in neonates. Improvement of the different steps, i.e. total DNA extraction, amplification in terms of efficiency and reduction of heteroduplex formation, TTGE migration conditions and bacterial identification from TTGE patterns, was performed. The optimized protocol was used for the subsequent analysis of 14 stool samples comparatively to a culture-based method. We showed that a specifically designed ladder representative of the diversity of the studied microflora is a useful tool for the identification of bacterial taxa despite biases inherent to 16S rRNA genes, including intra-genomic heterogeneity. Cultivation and PCR-TTGE gave congruent results but cultivation was more efficient for the detection of minor populations whereas PCR-TTGE gave a more complete description of the major populations. Finally, we demonstrated the reliability, the detection sensitivity and the convenience of the optimized 16S rDNA PCR-TTGE method compared with cultural approaches for studying the premature neonate gut microbiota.