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A letter to the editor is presented in response to the article "Probiotics for prevention of atopic diseases in infants: systematic review and meta-analysis" by G. Zuccotti and others, in a 2015 issue.

A stepwise approach is currently considered the best choice to manage gastroesophageal reflux (GER) in preterm infants. This study aimed to evaluate the effect of different tube feeding techniques on GER frequency and features in symptomatic tube-fed preterm neonates. Tube-fed infants < 34 weeks' gestation were eligible for this prospective, bicentric, cross-over study if, due to GER symptoms, they underwent a diagnostic 24-h combined pH and multiple intraluminal impedance (pH-MII) monitoring. During the monitoring period, each infant received the same feeding cycle, repeated twice: continuous tube feeding, bolus feeding followed by tube feeding permanence and by tube feeding removal. The impact of these three feeding modalities on pH-MII GER features was assessed. Thirty-one infants were enrolled. Despite a low number of reflux episodes, a significant decrease in total GERs (P < 0.001), in GERs detected by pH monitoring (P < 0.001), and in both acid and non-acid GERs detected by MII (P < 0.001 and P = 0.009, respectively) was observed in association with continuous feeding compared to bolus feeds, followed or not by tube feeding removal. Compared to continuous feeding, both bolus feeding modalities were associated with a significantly higher number of proximal GERs (P < 0.001). No difference in any pH-MII parameter was observed in relation to tube feeding persistence after bolus feeding administration., Conclusions: Continuous feeding and boluses may have a different impact on pH-MII GER features in symptomatic tube-fed preterm infants, whereas the permanence of the feeding tube across LES did not seem to worsen GER indexes., What Is Known: • Due to the functional and anatomical immaturity of the gastrointestinal tract, gastroesophageal reflux (GER) is common in preterm infants. • A stepwise therapeutical approach which firstly undertakes conservative strategies is the most advisable choice to avoid potentially harmful pharmacological overtreatments in the preterm population., What Is New: • Continuous feeding and boluses may have a different impact on GER features assessed by pH-MII monitoring in tube-fed preterm infants. • The permanence of the feeding tube during or after the feeding period did not seem to worsen GER occurrence. • By reducing GER features, especially acid GER, continuous feeding may potentially contribute to limit the need for antiacid medications in this population., (© 2024. The Author(s).)

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.

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.

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., (© 2023 S. Karger AG, Basel.)

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., (© 2023. The Author(s).)

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., (© 2022. The Author(s).)

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 28 5/7 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 (27 4/7 vs. 29 0/7 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., (© 2021 Wiley Periodicals LLC.)

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 Fio 2 ratio, Fio 2 , and Silverman score for surfactant administration were evaluated using receiver operating characteristic curves. The simultaneous prognostic values of LUS and oxygen saturation to Fio 2 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 Fio 2 , oxygen saturation to Fio 2 ratio, LUS, and Silverman scores as criteria for surfactant administration, only the latter showed a significantly poorer performance. The combination of oxygen saturation to Fio 2 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 Fio 2 ratio significantly improves the prediction power for surfactant need., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)