Tolerance and Safety of an Anti-Regurgitation Formula Containing Locust Bean Gum, Pre-, and Postbiotics: A Multi-Country Multi-Center Prospective Randomized Controlled Study in Infants with Regurgitation.

This multi-center prospective randomized controlled trial was a tolerance and safety study investigating the thickener locust bean gum (LBG) in infants with regurgitation, to support the re-evaluation of the safety of LBG in infant formula. The primary objective was to demonstrate that after an 8-week intervention, stool consistency was not inferior (i.e., was not looser or more watery) in infants fed an anti-regurgitation (AR) formula containing LBG vs. the stool consistency of infants fed with an unthickened control formula. A total of 103 full-term infants with regurgitation were randomized to the test or control formula. The test formula contained LBG (0.4 g/100 mL), short-chain galacto-oligosaccharides, and long-chain fructo-oligosaccharides (scGOS/lcFOS; 9:1; 0.4 g/100 mL) and postbiotics and the control formula contained scGOS/lcFOS (0.8 g/100 mL), the same amount of postbiotics, and did not contain LBG. The average stool consistency score at the 8th intervention week was the primary outcome parameter. Secondary outcome parameters were stool consistency at other timepoints, stool frequency, Infant Gastrointestinal Symptom Questionnaire (IGSQ) score, growth, (serious) adverse events ([S]AEs), regurgitation severity, and infant well-being. Overall, the infants were 36.9 ± 12.9 [mean ± SD] days old, 62.7% girls in the test, and 50.0% girls in the control group. The primary analysis showed that the test group did not have looser or more watery stools than the control group. IGSQ sum scores decreased comparably in both groups. The frequency of regurgitation was significantly lower in the test group compared to the control group (mixed model repeated measurement, p ≤ 0.028) and parent-reported well-being scores were favorable. Adequate growth was observed in both groups. Both products were well-tolerated and safe and the AR formula with LBG was efficacious in reducing regurgitation frequency. This study provides further evidence for the dietary management of regurgitation by LBG-containing formulae in infants who are not exclusively breastfed, and the reassurance it can bring to parents.

Preterm Infants' Airway Microbiome: A Scoping Review of the Current Evidence.

The aim of this scoping review was to investigate and synthesize existing evidence on the airway microbiome of preterm infants to outline the prognostic and therapeutic significance of these microbiomes within the preterm population and identify gaps in current knowledge, proposing avenues for future research. We performed a scoping review of the literature following the Arskey and O'Malley framework. In accordance with our inclusion criteria and the intended purpose of this scoping review, we identified a total of 21 articles. The investigation of the airway microbiome in preterm infants has revealed new insights into its unique characteristics, highlighting distinct dynamics when compared to term infants. Perinatal factors, such as the mode of delivery, chorioamnionitis, the respiratory support, and antibiotic treatment, could impact the composition of the airway microbiome. The 'gut-lung axis', examining the link between the lung and gut microbiome as well as modifications in respiratory microbiome across different sites and over time, has also been explored. Furthermore, correlations between the airway microbiome and adverse outcomes, such as bronchopulmonary dysplasia (BPD), have been established. Additional research in neonatal care is essential to understand the early colonization of infants' airways and explore methods for its optimization. The critical opportunity to shape long-term health through microbiome-mediated effects likely lies within the neonatal period.

External Validation of a Multivariate Model for Targeted Surfactant Replacement.

INTRODUCTION: Early targeted surfactant therapy for preterm infants is recommended but the best criteria to personalize treatment are unclear. We validate a previously published multivariate prognostic model based on gestational age (GA), lung ultrasound score (LUS), and oxygen saturation to inspire oxygen fraction ratio (SatO2/FiO2) using an independent data set. METHODS: Pragmatic, observational study in 10 Italian and Spanish NICUs, including preterm babies (250 and 336 weeks divided into 3 GA intervals) with clinical signs of respiratory distress syndrome and stabilized on CPAP. LUS and SatO2/FiO2 were collected soon after stabilization. Their prognostic accuracy was evaluated on the subsequent surfactant administration by a rigorously masked physician. RESULTS: One hundred seventy-five infants were included in the study. Surfactant was given to 74% infants born at 25-27 weeks, 38.5% at 28-30 weeks, and 26.5% at 31-33 weeks. The calibration curve comparing the validation and the development populations showed significant overlap with an intercept = 0.08, 95% CI (-0.34; 0.5) and a slope = 1.53, 95% CI (1.07-1.98). The validation cohort had a high predictive accuracy. Its ROC curve showed an AUC = 0.95, 95% CI (0.91-0.99) with sensitivity = 0.93, 95% CI (0.83-0.98), specificity = 0.81, 95% CI (0.73-0.88), PPV = 0.76, 95% CI (0.65-0.84), NPV = 0.95, 95% CI (0.88-0.98). LUS ≥9 demonstrated the highest sensitivity (0.91, 95% CI [0.82-0.97]) and specificity = 0.81, 95% CI (0.72-0.88) as individual predictor. LUS and SatO2/FiO2 prognostic performances varied with GA. CONCLUSION: We validated a prognostic model based on LUS and Sat/FiO2 to facilitate early, customized surfactant administration that may improve respiratory management of preterm neonates.

Relevance of sonographic parameters for inflammatory bowel disease in children.

PURPOSE: Intestinal ultrasound (IUS) is widely used as the first exam in patients with suspected inflammatory bowel disease (IBD). This study investigated the accuracy of several IUS parameters, including increased bowel wall thickening (BWT), in detecting IBD in a paediatric population. METHODS: The study included an unselected series of 113 patients aged 2-18 years (mean age 10.8 years, 65 male), referred for recurrent abdominal pain or altered bowel habits, without known organic diseases, to perform an IUS as first investigation of a diagnostic workup. Patients with full systematic IUS examination, clinical and biochemical exams, and ileocolonoscopy or an uneventful follow-up at least one year follow up were eligible. RESULTS: 23 IBD patients (20.4%; 8 ulcerative colitis, 12 Crohn's disease and 3 indeterminate colitis) were diagnosed. We found that increased BWT > 3 mm (OR 5.4), altered IUS bowel pattern (IUS-BP, OR 9.8) and mesenteric hypertrophy (MH, OR 5.2) accurately identified IBD at the multivariate analysis. IUS-BP, MH and BWT > 3 mm had a sensitivity of 78.3%, 65.2% and 69.6% and a specificity of 93.3%, 92.2% and 96.7%, respectively. The combination of these three alterations increased the specificity up to 100%, whilst decreased sensitivity to 56.5%. CONCLUSION: Among several US parameters suggestive of IBD, the increased BWT, MH and altered echopattern are independent predictors of IBD. The ultrasonographic diagnosis of IBD could be more accurate if relied on combination of different sonographic parameters, than on the sole BWT evaluation.

Increase of Parkin and ATG5 plasmatic levels following perinatal hypoxic-ischemic encephalopathy.

Brain injury at birth is an important cause of neurological and behavioral disorders. Hypoxic-ischemic encephalopathy (HIE) is a critical cerebral event occurring acutely or chronically at birth with high mortality and morbidity in newborns. Therapeutic strategies for the prevention of brain damage are still unknown, and the only medical intervention for newborns with moderate-to-severe HIE is therapeutic hypothermia (TH). Although the neurological outcome depends on the severity of the initial insult, emerging evidence suggests that infants with mild HIE who are not treated with TH have an increased risk for neurodevelopmental impairment; in the current clinical setting, there are no specific or validated biomarkers that can be used to both correlate the severity of the hypoxic insult at birth and monitor the trend in the insult over time. The aim of this work was to examine the presence of autophagic and mitophagic proteins in bodily fluids, to increase knowledge of what, early at birth, can inform therapeutic strategies in the first hours of life. This is a prospective multicentric study carried out from April 2019 to April 2020 in eight third-level neonatal intensive care units. All participants have been subjected to the plasma levels quantification of both Parkin (a protein involved in mitophagy) and ATG5 (involved in autophagy). These findings show that Parkin and ATG5 levels are related to hypoxic-ischemic insult and are reliable also at birth. These observations suggest a great potential diagnostic value for Parkin evaluation in the first 6 h of life.

Esophageal impedance baseline in infants with bronchopulmonary dysplasia: A pilot study.

BACKGROUND: Bronchopulmonary dysplasia (BPD) may induce gastroesophageal reflux (GER). Esophageal impedance baseline values (BI) reflect mucosal inflammation. Our aim was to evaluate BI levels in preterm infants with BPD compared with those without BPD and to identify BI predictors. METHODS: This is a retrospective pilot study including infants born <32 weeks' gestational age (GA) who underwent esophageal multichannel intraluminal impedance (MII)-pH. Univariate/multivariate analysis were performed to compare data between BPD and non-BPD infants and to identify BI predictors. A subgroup analysis was performed in infants born <29 weeks' GA, at highest risk for BPD. RESULTS: Ninety-seven patients (median GA 285/7 weeks, mean postnatal age 49 days, 29 with BPD), were studied. BPD infants had significantly lower birth weight compared with non-BPD infants (750 vs. 1275 g), were more immature (274/7 vs. 290/7 weeks GA), were older at MII-pH (79 vs. 38 days) and received less fluids during MII-pH (147 vs. 161 ml/kg/day). The same findings were found in the group of 53 infants born <29 weeks. BPD versus non-BPD infants had significantly lower BI (2050 vs. 2574 ohm, p = 0.007) (<1000 ohm in five BPD infants vs. one non-BPD) whereas the other MII-pH parameters were not significantly different. Multiple regression analysis found that increasing chronological age was positively associated with BI (B = 9.3, p = 0.013) whereas BPD was associated with lower BI (B = -793.4, p < 0.001). CONCLUSIONS: BPD versus non-BPD infants had significantly lower BI despite similar MII-pH data. BPD and chronological age predicted BI, whereas only BPD predicted BI in the most immature infants.

Management of asymptomatic hypoglycemia with 40% oral dextrose gel in near term at-risk infants to reduce intensive care need and promote breastfeeding.

BACKGROUND: Neonatal hypoglycemia is a common disorder especially in at-risk infants and it can be associated with poor long-term neurological outcomes. Several therapeutic interventions are suggested, from the implementation of breastfeeding to the glucose intravenous administration. Oral dextrose gel massaged into the infant's inner cheek is a recent treatment option of asymptomatic hypoglycemia, after which oral feeding is encouraged. This approach seems to reduce the admission of infants to neonatal intensive care unit (NICU) so favouring maternal bonding and breastfeeding success at discharge. METHODS: In our ward, we prospectively compared a group of near-term neonates, (Gr2, n = 308) at risk for hypoglycemia, treated with an innovative protocol based on the addition of 40% oral dextrose gel (Destrogel, Orsana®,Italy) administered by massaging gums and cheek with historical matching newborns (Gr1, n = 389) treated with a formerly used protocol, as control group. The primary outcome was occurrence of NICU admission and the requirement of intravenous glucose administration; while discharge with full breastfeeding was the secondary outcome. RESULTS: In Gr1, 39/389 (10%) infants presented with asymptomatic hypoglycemia, 19/39 were transferred to the NICU, and 14/39 required intravenous glucose treatment. In Gr2, among the 30/308 infants with asymptomatic hypoglycemia managed according to the new protocol, 3/30 were transferred to the NICU and received intravenous glucose infusion. The mean duration of hospitalization respectively was 6.43 (± 6.36) and 3.73 ± 1.53 days (p <  0.001). At discharge, 7.7% of the infants in Gr1 and 30% of the infants in Gr2 were exclusively breastfed (p = 0.02). Considering Gr1 vs Gr2, the number of patients that were transferred to NICU was 19 (48.7%) vs 3 (10%) (p = 0.001) and the number of infants that needed intravenous glucose infusion was 14 (35.9%) vs 3 (10%) (p = 0.01), respectively. CONCLUSIONS: In our population of near term infants, the introduction of 40% oral dextrose gel to the protocol, helped in the safe management of asymptomatic hypoglycemia and, at the same time, implemented breastfeeding.

Neonatal Lung Ultrasound and Surfactant Administration: A Pragmatic, Multicenter Study.

BACKGROUND: Previous research shows that a lung ultrasound score (LUS) can anticipate CPAP failure in neonatal respiratory distress syndrome. RESEARCH QUESTION: Can LUS also predict the need for surfactant replacement? STUDY DESIGN AND METHODS: Multicenter, pragmatic study of preterm neonates who underwent lung ultrasound at birth and those given surfactant by masked physicians, who also were scanned within 24 h from administration. Clinical data and respiratory support variables were recorded. Accuracy of LUS, oxygen saturation to Fio2 ratio, Fio2, and Silverman score for surfactant administration were evaluated using receiver operating characteristic curves. The simultaneous prognostic values of LUS and oxygen saturation to Fio2 ratio for surfactant administration, adjusting for gestational age (GA), were analyzed through a logistic regression model. RESULTS: Two hundred forty infants were enrolled. One hundred eight received at least one dose of surfactant. LUS predicted the first surfactant administration with an area under the receiver operating characteristic curve (AUC) of 0.86 (95% CI, 0.81-0.91), cut off of 9, sensitivity of 0.79 (95% CI, 0.70-0.86), specificity of 0.83 (95% CI, 0.76-0.89), positive predictive value of 0.79 (95% CI, 0.71-0.87), negative predictive value of 0.82 (95% CI, 0.75-0.89), positive likelihood ratio of 4.65 (95% CI, 3.14-6.89), and negative likelihood ratio of 0.26 (95% CI, 0.18-0.37). No significant difference was shown among different GA groups: 25 to 27 weeks' GA (AUC, 0.91; 95% CI, 0.84-0.99), 28 to 30 weeks' GA (AUC, 0.81; 95% CI, 0.72-0.91), and 31 to 33 weeks' GA (AUC, 0.88; 95% CI, 0.79-0.95), respectively. LUS declined significantly within 24 h in infants receiving one surfactant dose. When comparing Fio2, oxygen saturation to Fio2 ratio, LUS, and Silverman scores as criteria for surfactant administration, only the latter showed a significantly poorer performance. The combination of oxygen saturation to Fio2 ratio and LUS showed the highest predictive power, with an AUC of 0.93 (95% CI, 0.89-0.97), regardless of the GA interval. INTERPRETATION: LUS is a reliable criterion to administer the first surfactant dose regardless of GA. Its association with oxygen saturation to Fio2 ratio significantly improves the prediction power for surfactant need.

Nutritional status of children and adolescents in three Serbian enclaves in Kosovo and Metohija.

OBJECTIVE: To evaluate nutritional status of children and adolescents living in three Serbian enclaves in Kosovo and Metohija. METHODS: We conducted an observational cross-sectional, population-based study, enrolling children and adolescents who underwent a pediatric screening performed in the three Serbian enclaves of Gracanica, Gornje Kusce and Velika Hoca in Kosovo and Metohija. Children and adolescents (5-19 years) of all ethnic groups were evaluated in one of the three free outpatient medical facilities in rural villages in Kosovo. Body weight and height were measured, height-for-age z- scores (HAZ) and BMI-for-age z-scores (BAZ) indicators were analyzed. The anthropometric indicators HAZ and BAZ distributions were compared between sex and ages using Fisher's exact test. A two-sample Z-test for proportions was used to detect differences in individual categories of height- and BMI-for-age categories across sexes and age classes. RESULTS: Three hundred twenty-eight children and adolescents (184 females, 56.1% and 144 males, 43.9%) aged between 5 and 19 years were enrolled in the study. 241/328 participants showed a normal linear growth; with significantly more girls (78.3%) than boys (67.4%) being in the normal category. Similarly, a significant difference in BAZ distribution between sexes was noted, with more females being in the normal BMI category compared to males (63.0% vs 50.0%, respectively). Underweight and severe underweight subjects showed a prevalence of 1.5 and 0.6%, respectively. Overweight and obesity prevalence was 19.5 and 9.1%, respectively, which was comparable to World Health Organization overweight and obesity prevalence data for Serbia. CONCLUSIONS: Prevalence of undernutrition and severe undernutrition in children and adolescents living in three Serbian enclaves in Kosovo and Metohija is small. By contrast, a tendency to an increase in overweight and obesity, especially in the male population, was noted.

Lung Ultrasound Score Progress in Neonatal Respiratory Distress Syndrome.

BACKGROUND AND OBJECTIVES: The utility of a lung ultrasound score (LUS) has been described in the early phases of neonatal respiratory distress syndrome (RDS). We investigated lung ultrasound as a tool to monitor respiratory status in preterm neonates throughout the course of RDS. METHODS: Preterm neonates, stratified in 3 gestational age cohorts (25-27, 28-30, and 31-33 weeks), underwent lung ultrasound at weekly intervals from birth. Clinical data, respiratory support variables, and major complications (sepsis, patent ductus arteriosus, pneumothorax, and persistent pulmonary hypertension of the neonate) were also recorded. RESULTS: We enrolled 240 infants in total. The 3 gestational age intervals had significantly different LUS patterns. There was a significant correlation between LUS and the ratio of oxygen saturation to inspired oxygen throughout the admission, increasing with gestational age (b = -0.002 [P < .001] at 25-27 weeks; b = -0.006 [P < .001] at 28-30 weeks; b = -0.012 [P < .001] at 31-33 weeks). Infants with complications had a higher LUS already at birth (12 interquartile range 13-8 vs 8 interquartile range 12-4 control group; P = .001). In infants 25 to 30 weeks' gestation, the LUS at 7 days of life predicted bronchopulmonary dysplasia with an area under the curve of 0.82 (95% confidence interval 0.71 to 93). CONCLUSIONS: In preterm neonates affected by RDS, the LUS trajectory is gestational age dependent, significantly correlates with the oxygenation status, and predicts bronchopulmonary dysplasia. In this population, LUS is a useful, bedside, noninvasive tool to monitor the respiratory status.

Response to therapy among neonates with gastro-esophageal reflux is associated with esophageal clearance.

BACKGROUND: Few studies evaluated the efficacy of pharmacological therapy for gastro-esophageal reflux disease (GERD) in newborns, whose safety has been questioned. Esophageal basal impedance (BI) is a marker of mucosal integrity, and treatment with proton pump inhibitors significantly increases BI in infants; however, no correlation with clinical improvement was reported. AIMS: To evaluate the relationship between BI and other esophageal pH-impedance parameters and clinical response to therapy in newborns with GERD. STUDY DESIGN: Multicenter retrospective study. SUBJECTS: Infants who received omeprazole or ranitidine for GERD. OUTCOME MEASURES: Complete response to therapy was defined as symptom decrease by ≥50% compared to baseline, partial response as symptom decrease <50%, no response as no symptom decrease based on chart analysis. Response to therapy was assessed 2 and 4 weeks after the onset of therapy. Univariate and multivariate statistics were performed to assess associations between response to therapy and clinical/pH-impedance parameters. RESULTS: We studied 60 infants (51 born preterm): 47 received omeprazole, 13 ranitidine. Response to therapy was associated with decreasing esophageal clearance time: odds ratio 0.308, 95%CI 0.126-0.753, p = 0.010 at 2 weeks, odds ratio 0.461, 95%CI 0.223-0.955, p = 0.037 at 4 weeks. CONCLUSIONS: Clinical response to therapy among infants with GERD was associated with esophageal clearance but not with esophageal BI level.

Birth Weight and the Development of Functional Gastrointestinal Disorders in Infants.

PURPOSE: To assess the association between birth weight and the development of functional gastrointestinal disorders (FGIDs) in the first year of life. METHODS: This is a secondary analysis of a prospective cohort multicenter study including neonates, consecutively enrolled at birth, and followed up for one year. At birth all infants were classified by birth weight as extremely low (ELBW), very low, or low when <1,000, <1,500, and <2,500 g, respectively, and by birth weight for gestational age as appropriate (AGA, weight in the 10-90th percentile), small (SGA, weight <10th percentile), and large (LGA, weight >90th percentile) for gestational age. FGIDs were classified according to the Rome III criteria and assessed at 1, 3, 6, and 12 months of life. RESULTS: Among 1,152 newborns enrolled, 934 (81.1%) completed the study: 302 (32.3%) were preterm, 35 (3.7%) were ELBW, 104 (11.1%) were SGA, 782 (83.7%) were AGA, and 48 (5.1%) were LGA infants. Overall, throughout the first year of life, 718 (76.9%) reported at least one FGID. The proportion of infants presenting with at least one FGID was significantly higher in ELBW (97%) compared to LBW (74%) (p=0.01) and in LGA (85.4%) and SGA (85.6%) compared to AGA (75.2%) (p=0.0001). On multivariate analysis, SGA was significantly associated with infantile colic. CONCLUSION: We observed an increased risk of FGIDs in ELBW, SGA, and LGA neonates. Our results suggest that prenatal factors determining birth weight may influence the development of FGIDs in infants. Understanding the role of all potential risk factors may provide new insights and targeted approaches for FGIDs.

Laryngeal signs and pH-multichannel intraluminal impedance in infants and children: The missing ring: LPR and MII-pH in children.

OBJECTIVE: to investigate the reliability of laryngeal reflux finding score (RFS) and symptom index (RSI) in assessing gastroesophageal reflux (GER) in children and infants. METHODS: patients with laryngeal or respiratory symptoms, who underwent laryngoscopy and esophageal pH-impedance (MII-pH) were recruited. RSI and RFS were correlated to MII-pH results. A RSI>13, RFS>7, acid exposure index>7%, total reflux episodes>100/24 h in infants or>70/24 h in children, or a positive symptom index or association probability, were considered pathological. Analysis considering age (12 months) was performed. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of the laryngeal scores were calculated. RESULTS: 197 children (median 53 months, 61 infants) were enrolled. MII-pH was pathological in 5/10 patients with RFS>7, and in 17/31 with RSI>13. RFS>7 had 3.9% sensitivity, 93% specificity, a PPV of 50 and a NPV of 34 in predicting GER disease. RFS was inversely associated to weakly acidic and proximal GER. RSI>13 had 13% sensitivity, 83% specificity, and a PPV and NPV similar to RFS. RSI was significantly associated with the number of acid reflux episodes, and, in infants, with bolus exposure index. CONCLUSIONS: RSI and RFS aren't accurate in predicting GER in infants and children. Acid reflux relates to laryngeal symptoms, but neither acid, nor proximal and weakly acidic GER relate to laryngeal alterations.

Neonatal Antibiotics and Prematurity Are Associated with an Increased Risk of Functional Gastrointestinal Disorders in the First Year of Life.

OBJECTIVE: To assess the prevalence of functional gastrointestinal disorders (FGIDs) in the first year of life and the influence of different neonatal factors on development of FGIDs. STUDY DESIGN: A prospective cohort multicenter study including neonates, consecutively enrolled at birth, and followed up until 1 year. Gestational age, neonatal antibiotic administration, duration of hospitalization, mode of delivery, birth weight, and feeding pattern were recorded. FGIDs were classified according to Rome III criteria and assessed at 1, 3, 6, and 12 months of life. RESULTS: Among 1152 newborns enrolled, 934 (81.1%) completed the study, 302 (32%) were newborns born preterm, 320 (34%) had neonatal antibiotics, and 718 (76.9%) had at least 1 FGID according to Rome III criteria (443 [47.4%] infantile colic, 374 [40.0%] regurgitation, 297 [31.8%] infant dyschezia, 248 [26.6%] functional constipation, and 34 [3.6%] functional diarrhea) throughout the first year of life. The proportion of infants born preterm presenting with FGIDs (86%) was significantly greater compared with infants born full term (72.5%) (χ2 = 21.3, P = .0001). On multivariate analysis, prematurity and neonatal use of antibiotics was significantly associated with at least 1 FGID. CONCLUSIONS: We found a high rate FGIDs in infants, likely related to the population recruited, the long observation period, the diagnosis based on Rome III criteria, and parental reports. Preterm delivery and neonatal use of antibiotics in the first months of life are associated with an increased incidence of FGIDs, particularly infantile colic and regurgitation. In our population, cesarean delivery and feeding pattern at 1 month of life emerged as additional risk factors for infant dyschezia and functional diarrhea. Other neonatal factors associated with FGIDs need to be further explored.

Noninvasive testing in the management of children with suspected inflammatory bowel disease.

Objective: To assess the accuracy of noninvasive parameters, fecal calprotectin (FC), increased bowel wall thickening (BWT) at intestinal ultrasound (IUS) and blood inflammatory indexes (BII), alone or in combination, as diagnostic tools for inflammatory bowel disease (IBD) in pediatric patients. Methods: Retrospective data were collected on consecutive children (age 2-18 years) referred to our pediatric gastroenterology clinic, for recurrent abdominal pain and/or altered bowel habit from 2007 to 2013. Subjects who had diagnostic workup: laboratory tests (FC, BII, white blood cell (WBC), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)) and IUS as initial assessment were eligible. Subjects with known gastrointestinal (GI) diseases, or signs or symptoms highly suggestive for organic diseases necessitating prompt endoscopy (e.g., perianal disease or rectal bleeding), or who had recently performed endoscopy were excluded. The accuracy of noninvasive tests for detecting IBD was assessed using endoscopic and/or radiological investigations, performed in subsequent clinical follow up, as reference gold standard. Results: Seventy-seven patients (mean age 11.3, 44 males) were included, 23 (29.9%) with a final diagnosis of IBD. As single tests, FC gave the highest sensitivity (96%) but lower specificity (72%) and IUS highest specificity (96%) with lower sensitivity (70%). The combination of FC + IUS showed excellent accuracy for detecting children with IBD with positive predictive value: 100%; negative predictive value: 88.5%. The probability of IBD in children with normal FC, BII and IUS was 0.09%. Conclusions: FC and increased BWT at IUS are accurate to guide reassurance or proceeding with further invasive procedures for detecting IBD in children with mild GI symptoms.

Enteral Nutrition Tolerance And REspiratory Support (ENTARES) Study in preterm infants: study protocol for a randomized controlled trial.

BACKGROUND: Respiratory distress syndrome (RDS) and feeding intolerance are common conditions in preterm infants and among the major causes of neonatal mortality and morbidity. For many years, preterm infants with RDS have been treated with mechanical ventilation, increasing risks of acute lung injury and bronchopulmonary dysplasia. In recent years non-invasive ventilation techniques have been developed. Showing similar efficacy and risk of bronchopulmonary dysplasia, nasal continuous positive airway pressure (NCPAP) and heated humidified high-flow nasal cannula (HHHFNC) have become the most widespread techniques in neonatal intensive care units. However, their impact on nutrition, particularly on feeding tolerance and risk of complications, is still unknown in preterm infants. The aim of the study is to evaluate the impact of NCPAP vs HHHFNC on enteral feeding and to identify the most suitable technique for preterm infants with RDS. METHODS: A multicenter randomized single-blind controlled trial was designed. All preterm infants with a gestational age of 25-29 weeks treated with NCPAP or HHHFNC for RDS and demonstrating stability for at least 48 h along with the compliance with inclusion criteria (age less than 7 days, need for non-invasive respiratory support, suitability to start enteral feeding) will be enrolled in the study and randomized to the NCPAP or HHHFNC arm. All patients will be monitored until discharge, and data will be analyzed according to an intention-to-treat model. The primary outcome is the time to reach full enteral feeding, while parameters of respiratory support, feeding tolerance, and overall health status will be evaluated as secondary outcomes. The sample size was calculated at 141 patients per arm. DISCUSSION: The identification of the most suitable technique (NCPAP vs HHHFNC) for preterm infants with feeding intolerance could reduce gastrointestinal complications, improve growth, and reduce hospital length of stay, thus improving clinical outcomes and reducing health costs. The evaluation of the timing of oral feeding could be useful in understanding the influence that these techniques could have on the development of sucking-swallow coordination. Moreover, the evaluation of the response to NCPAP and HHHFNC could clarify their efficacy as a treatment for RDS in extremely preterm infants. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03548324 . Registered on 7 June 2018.

Weaning Time in Preterm Infants: An Audit of Italian Primary Care Paediatricians.

INTRODUCTION: According to the 2016 Italian National Institute of Statistics (Istat) data in Italy, about 6.7% of all newborns are born prematurely. Due to the lack of data on current complementary feeding in preterm infants in Italy, the aim of the survey was to evaluate individual attitudes of primary care paediatricians, concerning the introduction of complementary foods in preterm infants. METHODS: An internet-based survey was conducted among primary care paediatricians, working in Italy, regarding (1) timing of the introduction of complementary foods to preterm newborns; (2) type of complementary foods introduced; (3) vitamin D and iron supplementations. RESULTS: A total of 347 primary care Italian paediatricians answered the questionnaire; 44% of responders based the timing of the introduction of solid food exclusively on an infant's age, 18% on an infant's neurodevelopmental status and 4% on the body weight; the remaining 34% based the timing on two or more of these aspects. The type of complementary foods did not comply with an evidence-based sequence; 98% of participants promoted vitamin D supplementation and 89% promoted iron supplementation with great diversity in timing and doses. CONCLUSIONS: Due to limited evidence, there is a great heterogeneity in the attitudes of primary care paediatricians concerning the introduction of complementary foods to preterm newborns. Further research is needed to provide evidence-based guidelines regarding weaning preterm newborns.

Probiotics Prevent Late-Onset Sepsis in Human Milk-Fed, Very Low Birth Weight Preterm Infants: Systematic Review and Meta-Analysis.

Growing evidence supports the role of probiotics in reducing the risk of necrotizing enterocolitis, time to achieve full enteral feeding, and late-onset sepsis (LOS) in preterm infants. As reported for several neonatal clinical outcomes, recent data have suggested that nutrition might affect probiotics' efficacy. Nevertheless, the currently available literature does not explore the relationship between LOS prevention and type of feeding in preterm infants receiving probiotics. Thus, the aim of this systematic review and meta-analysis was to evaluate the effect of probiotics for LOS prevention in preterm infants according to type of feeding (exclusive human milk (HM) vs. exclusive formula or mixed feeding). Randomized-controlled trials involving preterm infants receiving probiotics and reporting on LOS were included in the systematic review. Only trials reporting on outcome according to feeding type were included in the meta-analysis. Fixed-effects models were used and random-effects models were used when significant heterogeneity was found. The results were expressed as risk ratio (RR) with 95% confidence interval (CI). Twenty-five studies were included in the meta-analysis. Overall, probiotic supplementation resulted in a significantly lower incidence of LOS (RR 0.79 (95% CI 0.71-0.88), p < 0.0001). According to feeding type, the beneficial effect of probiotics was confirmed only in exclusively HM-fed preterm infants (RR 0.75 (95% CI 0.65-0.86), p < 0.0001). Among HM-fed infants, only probiotic mixtures, and not single-strain products, were effective in reducing LOS incidence (RR 0.68 (95% CI 0.57-0.80) p < 0.00001). The results of the present meta-analysis show that probiotics reduce LOS incidence in exclusively HM-fed preterm infants. Further efforts are required to clarify the relationship between probiotics supplementation, HM, and feeding practices in preterm infants.

Functional nutrients in infants born by vaginal delivery or Cesarean section.

The development of a proper neonatal microbiota is of great importance, especially for the effects that dysbiosis has in acute and chronic diseases' onset. The microbiota, particularly the intestinal one, plays a crucial role in maintaining the health of the host, preventing colonization by pathogenic bacteria and significantly influencing the development and maturation of a normal gastrointestinal mucosal immunity. Several factors may interfere with the physiological development of microbiota, such as diseases during pregnancy, type of delivery, maternal nutrition, type of neonatal feeding, use of antibiotics, exposition to hospital environment (e.g., neonatal intensive care unit) and genetic factors. Thanks to a proper maternal and neonatal supplementation with specific functional nutrients, it is now possible to correct dysbiosis, thus reducing the risks for the newborn's health. In this review of the literature, we give an overview of the studies highlighting the composition of the maternal, fetal and neonatal microbiota, the factors potentially responsible for dysbiosis and the use of functional nutrients to prevent diseases' onset.

Nutritional problems of children with bronchopulmonary dysplasia after hospital discharge.

The last decades have seen significant improvements in the care of premature infants. The introduction of new approaches, especially in the ventilatory management, have led to significant increase of survival rate of low and extremely low gestational age infants. These populations of neonates, however, often experience prolonged mechanical ventilation, which is widely recognized to be closely related to bronchopulmonary dysplasia (BPD) development. The management of BPD, which is a multifactorial disease, requires a multidisciplinary approach and remains challenging for all the physicians involved. In fact, short and long-term sequelae are not only related to pulmonary performances but include neurological impairment and growth deficiency. A proper nutrition management since the very first days has shown to significantly contribute to the optimal maturation and functionality of the lung. In this paper, we aim to give an overall of the main principles of nutrition in infants born prematurely, with specific regard to the interventions, which could be relevant in infants affected by BPD.