Disrupted Seasonality of Respiratory Viruses: Retrospective Analysis of Pediatric Hospitalizations in Italy from 2019 to 2023.

This multicenter study in Italian hospitals highlights the epidemiologic disruptions in the circulation of the 5 main respiratory viruses from 2019 to 2023. Our data reveal a resurgence of respiratory syncytial virus and influenza during the 2022-2023 winter season, with an earlier peak in cases for both viruses, emphasizing the importance of timely monitoring.

Fetal to neonatal transition: what additional information can be provided by cerebral near infrared spectroscopy?

This narrative review focuses on the clinical use and relevance of cerebral oxygenation measured by NIRS during fetal to neonatal transition. Cerebral NIRS(cNIRS) offers the possibility of non-invasive, continuous, and objective brain monitoring in addition to the recommended routine monitoring. During the last decade, with growing interest in early and sensitive brain monitoring, many research groups worldwide have been working with cNIRS and verified the feasibility of cNIRS monitoring immediately after birth. Cerebral hypoxia during fetal to neonatal transition, defined as cerebral oxygenation values below10th percentile, seems to have an impact on neurological outcomes. Feasibility to guide clinical support using cNIRS to reduce the burden of cerebral hypoxia has been shown. It is well known that in some cases cerebral oxygenation follows different patterns than SpO2. Cerebral oxygenation does not only depend on systemic oxygenation, hemoglobin content and cerebral blood flow, but also on cardiocirculatory condition, ventilation, and metabolic parameters. Hence, measurement of cerebral oxygenation may uncover problems not detectable by standard monitoring. Therefore, applying NIRS can provide caregivers a more complete clinical overview, especially in critically ill neonates. In this review, we aim to describe the additional information which can be provided by cNIRS during fetal to neonatal transition. IMPACT: This narrative review focuses on the clinical use and relevance of cerebral oxygenation measured by near infrared spectroscopy (NIRS) during fetal to neonatal transition. During the last decade, interest on brain monitoring is growing continuously as the measurement of cerebral oxygenation may uncover problems which are not detectable by routine monitoring. Therefore, it will be crucial to have additional information to get a complete overview, especially in critically ill neonates in need of medical and respiratory support. In this review, we offer additional information which can be provided by cerebral NIRS during fetal to neonatal transition.

Different Settings of Nonsynchronized Bilevel Nasal Continuous Positive Airway Pressure and Respiratory Function in Preterm Infants: A Pilot Study.

OBJECTIVE: With this study, we evaluated the short-term effects of different modes and settings of noninvasive respiratory support on gas exchange, breathing parameters, and thoracoabdominal synchrony in preterm infants in the acute phase of moderate respiratory distress syndrome. STUDY DESIGN: A feasibility crossover trial was conducted in neonates < 32 weeks' gestation on nasal continuous positive airway pressure (n-CPAP) or bilevel n-CPAP. Infants were delivered the following settings in consecutive order for 10 minutes each: • n-CPAP (5 cm H2O) • bilevel n-CPAP 1 (Pres low = 5 cm H2O, Pres high = 7 cm H2O, T-high = 1 second, rate = 30/min) • n-CPAP (5 cm H2O) • bilevel n-CPAP 2 (Pres low = 5 cm H2O, Pres high = 7 cm H2O, T-high = 2 second, rate = 15/min) • n-CPAP (5 cm H2O). During each phase, physiologic parameters were recorded; the thoracoabdominal synchrony expressed by the phase angle (Φ) and other respiratory patterns were monitored by noncalibrated respiratory inductance plethysmography. RESULTS: Fourteen preterm infants were analyzed. The mean CPAP level was significantly lower in the n-CPAP period compared with bilevel n-CPAP 1 and 2 (p = 0.03). Higher values were achieved with bilevel n-CPAP 2 (6.2 ± 0.6 vs. 5.7 ± 0.5 cm H2O, respectively; p < 0.05). No statistical difference in the Φ was detected, nor between the three settings. CONCLUSION: Our study did not show any superiority of bilevel n-CPAP over n-CPAP. However, nonsynchronized bilevel n-CPAP might be helpful when additional pressure is needed. KEY POINTS: · There is currently a high degree of uncertainty about the superiority of one modality and setting of noninvasive respiratory over another.. · Our study confirmed that non-synchronized bilevel n-CPAP might be helpful when additional pressure is needed for recruitment.. · A T-high of 1 second could possibly be better tolerated in this population, but further research is needed..

The Role of Virulence Factors in Neonatal Sepsis Caused by Enterobacterales: A Systematic Review.

Neonatal sepsis is a life-threatening condition with high mortality. Virulence determinants relevant in causing Gram-negative (GN) neonatal sepsis are still poorly characterized. A better understanding of virulence factors (VFs) associated with GN neonatal sepsis could offer new targets for therapeutic interventions. The aim of this review was to assess the role of GN VFs in neonatal sepsis. We primarily aimed to investigate the main VFs leading to adverse outcome and second to evaluate VFs associated with increased invasiveness/pathogenicity in neonates. MEDLINE, Embase, and Cochrane Library were systematically searched for studies reporting data on the role of virulome/VFs in bloodstream infections caused by Enterobacterales among neonates and infants aged 0-90 days. Twenty studies fulfilled the inclusion criteria. Only 4 studies reported data on the association between pathogen virulence determinants and neonatal mortality, whereas 16 studies were included in the secondary analyses. The quality of reporting was suboptimal in the great majority of the published studies. No consistent association between virulence determinants and GN strains causing neonatal sepsis was identified. Considerable heterogeneity was found in terms of VFs analysed and reported, included population and microbiological methods, with the included studies often showing conflicting data. This variability hampered the comparison of the results. In conclusions, pathogens responsible for neonatal sepsis are widely heterogenous and can use different pathways to develop invasive disease. The recent genome-wide approach needs to include multicentre studies with larger sample sizes, analyses of VF gene profiles instead of single VF genes, alongside a comprehensive collection of clinical information. A better understanding of the roles of virulence genes in neonatal GN bacteraemia may offer new vaccine targets and new markers of highly virulent strains. This information can potentially be used for screening and preventive interventions as well as for new targets for anti-virulence antibiotic-sparing therapies.

Surfactant lung delivery with LISA and InSurE in adult rabbits with respiratory distress.

BACKGROUND: In preterm infants, InSurE (Intubation-Surfactant-Extubation) and LISA (less invasive surfactant administration) techniques allow for exogenous surfactant administration while reducing lung injury associated with mechanical ventilation. We compared the acute pulmonary response and lung deposition of surfactant by LISA and InSurE in surfactant-depleted adult rabbits. METHODS: Twenty-six spontaneously breathing surfactant-depleted adult rabbits (6-7 weeks old) with moderate RDS and managed with nasal continuous positive airway pressure were randomized to 3 groups: (1) 200 mg/kg of surfactant by InSurE; (2) 200 mg/kg of surfactant by LISA; (3) no surfactant treatment (Control). Gas exchange and lung mechanics were monitored for 180 min. After that, surfactant lung deposition and distribution were evaluated monitoring disaturated-phosphatidylcholine (DSPC) and surfactant protein C (SP-C), respectively. RESULTS: No signs of recovery were found in the untreated animals. After InSurE, oxygenation improved more rapidly compared to LISA. However, at 180' LISA and InSurE showed comparable outcomes in terms of gas exchange, ventilation parameters, and lung mechanics. Neither DSPC in the alveolar pool nor SP-C signal distributions in a frontal lung section were significantly different between InSurE and LISA groups. CONCLUSIONS: In an acute setting, LISA demonstrated efficacy and surfactant lung delivery similar to that of InSurE in surfactant-depleted adult rabbits. IMPACT: Although LISA technique is gaining popularity, there are still several questions to address. This is the first study comparing LISA and InSurE in terms of gas exchange, ventilation parameters, and lung mechanics as well as surfactant deposition and distribution. In our animal study, three hours post-treatment, LISA method seems to be as effective as InSurE and showed similar surfactant lung delivery. Our findings provide some clarifications on a fair comparison between LISA and InSurE techniques, particularly in terms of surfactant delivery. They should reassure some of the concerns raised by the clinical community on LISA adoption in neonatal units.

Interventions to reduce occupational stress and burn out within neonatal intensive care units: a systematic review.

Occupational stress is an emerging problem among physician and nurses, and those working in intensive care settings are particularly exposed to the risk of developing burnout. To verify what types of interventions to manage occupational stress and burn out within neonatal intensive care units (NICUs) have been introduced so far and to verify their efficacy among caregivers. PsycINFO (PsycINFO 1967-July week 3 2019), Embase (Embase 1996-2019 week 29) e Medline (Ovid MEDLINE(R) without revisions 1996-July week 2 2019) were systematically searched combining MeSH and free text terms for "burn out" AND "healthcare provider" AND "NICU". Inclusion criteria were interventions directed to healthcare providers settled in NICUs. Only English language papers were included. Six articles were included in the final analysis. All the studies reported an overall efficacy of the interventions in reducing work-related stress, both when individual focused and organisation directed. The analysis revealed low quality of the studies and high heterogeneity in terms of study design, included populations, interventions and their evaluation assessment. There is currently very limited evidence regarding the management of occupational stress and burn out within NICUs. The quality of available studies was suboptimal. The peculiarities of the NICUs should be considered when developing strategies for occupational stress management. Training self-awareness of workers regarding their reactions to the NICU environment, also from the pre-employment stage, could be an additional approach to prevent and manage stress.

Acute ulceronecrotic adverse reaction to potassium hydroxide 5% solution in the treatment of molluscum contagiosum.

Molluscum contagiosum is a common childhood condition, and although it is self-limited, treatments are often prescribed. Several medications are available, but there is no consensus regarding the optimal choice in the pediatric population. We report a child who underwent potassium hydroxide 5% treatment resulting in superficial diffuse erosions caused by the inappropriate application. This underlines the importance of parent education before use of this medication with well-known caustic properties.

Respiratory Support of Neonate Affected by Bronchiolitis in Neonatal Intensive Care Unit.

Acute respiratory infections are very common medical emergency in early infancy, often requiring hospitalization. The most frequent respiratory infection at this stage of life is bronchiolitis, with a benign course in the majority of cases. However, especially during neonatal period, infants are at higher risk for developing complications, and ventilatory support of various degrees is needed. The two most widespread methods to provide noninvasive respiratory support are heated humidified high-flow nasal cannula and nasal continuous positive airway pressure. They are both used in neonatal intensive care unit to treat respiratory distress syndrome of the premature infants, and the main concept of recruiting and distending alveoli is valid also for respiratory failure occurring during bronchiolitis. However, there is still ongoing debate about the superiority of one method, and their real efficacy still need to be confirmed. Once respiratory failure does not respond to noninvasive ventilation, more intensive care must be provided in the form of conventional mechanical ventilation or high-frequency ventilation. There is currently no evidence of the optimal ventilation strategy to use, and a deeper comprehension of the pulmonary mechanics during bronchiolitis would be desirable to tailor ventilation according to the degree of severity. Further research is then urgently needed to better clarify these aspects. KEY POINTS: · Guidelines on the management of bronchiolitis in neonatal population are lacking.. · Noninvasive respiratory support is mostly delivered with HHHFNC and nCPAP.. · A deeper comprehension of the pulmonary mechanics during bronchiolitis is crucial to tailor invasive ventilation..

National surveys of UK and Italian neonatal units highlighted significant differences in the use of non-invasive respiratory support.

AIM: This study compared how non-invasive respiratory support (NRS) was provided in neonatal units in Italy and the UK. METHODS: An NRS questionnaire was sent to tertiary neonatal centres, identified by national societies, from November 2015 to May 2016. RESULTS: Responses were received from 49/57 (86%) UK units and 103/115 (90%) Italian units. NRS was started in the delivery room by 61% of UK units and 85% of Italian units. In neonatal intensive care units, 33% of UK units used nasal high-flow therapy (HFT) as primary support, compared to 3% in Italy. Nasal continuous positive airway pressure (CPAP) was used in 57% of UK units and 90% of Italian units. The commonest starting flow rate on nasal HFT for term and preterm infants was 6 L/min in the UK, while Italian units mainly used this flow for term infants. In the UK, 67% of units decreased nasal HFT by 1 L/min per day. In Italy, infants on nasal CPAP were weaned by 1 cm H2 O per day in 39% of units. CONCLUSION: The way that NRS was managed for very preterm infants differed between the UK and Italy, reflecting a lack of evidence on optimal NRS and the use of local protocols.

Full oral feeding is possible before discharge even in extremely preterm infants.

AIM: This study described the steps needed to achieve full oral feeding before discharge in a group of very and extremely preterm (EPT) infants. We analysed the effects of oral feeding skills on discharge timing and on weight gain during their neonatal intensive care unit (NICU) stay. METHODS: A prospective cross-sectional observational study of 100 infants who were <32 weeks of gestation (GA) was conducted at the Division of Neonatology, Graz, Austria, from March 2014 to February 2015. Patients were stratified into two groups: those who were <28 weeks at birth and those who were 28 weeks and over. Velocity of oral feeding skills attainment and weight gain were analysed. RESULTS: All infants successfully acquired oral feeding skills during hospitalisation. The median GA at which full oral feeding skills were reached was 37 + 1 weeks in EPT and 34 + 5 weeks in very preterm infants. More immature neonates showed worse feeding performances and lower weight increments during oral feeding steps. CONCLUSION: Our study confirmed the role of GA in the development of oral feeding skills in the most premature babies. It also raises the question of whether expected daily weight gain should be targeted according to GA.

Comparison between two ocular cleansing modalities in a population of newborns admitted to Neonatal Intensive Care Unit with clinical signs of conjunctivitis: a randomized controlled trial.

BACKGROUND: Neonatal conjunctivitis is frequent and could benefit from daily cleansing with saline. Anyway super infections can occur and therefore antibiotics are frequently needed. Recently alternative therapies (e.g. Echinacea angustifolia) are used for neonatal conjunctivitis to try to reduce antibiotics therapy. The aim of the study was to verify if the use of gauze containing Echinacea angustifolia compared to standard sodium-chloride at the onset of conjunctivitis symptoms is effective in reducing the clinical symptoms and the risk for superinfections. METHODS: The study was randomized and controlled. Neonates admitted in a tertiary level Neonatal Intensive Care Unit (NICU), with clinical signs of conjunctivitis during hospital stay, were randomized in two groups: group A (3 times daily ocular cleansing for 48 h with sterile gauze; group B (3 times daily ocular cleansing for 48 h with Iridium® baby gauze (Neoox) containing Echinacea angustifolia and pineapple sativus). An eye swab for cultural analysis was taken at time of presentation (T0) prior to treatment and at the end of ocular cleansing (T1). RESULTS: Sixty-three neonates were enrolled (GrA=30 and GrB=33). At T0, eye specimen positivity was found in 16/30 (48%) in group A and in 18/33 (55%) in group B (P=0.9). No statistical differences among groups at T0 regarding culture positivity. After 48 h, babies in Gr A have significantly fewer positive swabs compared to group B (group A: 18/29, group B: 10/32; P=0.009). Neonates in group B who had negative swab at T0 had a significantly reduced risk to have positive culture at T1 (OR 0.28, CI: 0.10-0,80, P=0.01), also considering confounding factors (birth weight, gestational age, mode of delivery) (adjusted OR 0.15, CI: 0.03-0.52, P<0.01). No differences in regard to antibiotic needs (P=0.95) during the course of conjunctivitis between groups. CONCLUSIONS: Our data suggest that these gauzes containing Echinacea angustifolia might help in avoiding super-infections, contaminations and in reducing ocular bacterial load.

Is Less Invasive Surfactant Administration Necessary or "Only" Helpful or Just a Fashion?

In the 1990s, the most relevant pillars in the treatment of neonatal respiratory distress syndrome (RDS) have been improvements in ventilation strategies, the introduction of exogenous surfactant replacement therapy, and the use of antenatal steroids. Lately, in addition to the standard INSURE (INtubation-SURfactant administration-Extubation) method to administer surfactant, a new technique has been gaining increasing popularity. It is the so-called less invasive surfactant administration (LISA) method, which has shown promising results in preventing bronchopulmonary dysplasia development and in reducing mortality in preterm neonates. The rationale behind this technique is to avoid positive pressure ventilation and the endotracheal tube, being surfactant delivered through a thin catheter while the neonate is maintained on continuous positive airway pressure. Given the paucity of large-scale randomized trials on LISA method to prove its effects on short- and long-term outcomes, some questions still remain unanswered. Then, uncertainty regarding the feasibility of this maneuver needs to be better clarified before gaining wide acceptance in routine clinical practice. In our report, we aim at hypothesizing the main mechanisms behind the efficacy of LISA, considering it as a single maneuver in a comprehensive approach for RDS management in the delivery room.

Effect of Cerebral Oximetry-Guided Treatment on Brain Injury in Preterm Infants as Assessed by Magnetic Resonance Imaging at Term Equivalent Age: An Ancillary SafeBoosC-III Study.

INTRODUCTION: The SafeBoosC-III trial investigated the effect of cerebral oximetry-guided treatment in the first 72 h after birth on mortality and severe brain injury diagnosed by cranial ultrasound in extremely preterm infants (EPIs). This ancillary study evaluated the effect of cerebral oximetry on global brain injury as assessed by magnetic resonance imaging (MRI) at term equivalent age (TEA). METHODS: MRI scans were obtained between 36 and 44.9 weeks PMA. The Kidokoro score was independently evaluated by two blinded assessors. The intervention effect was assessed using the nonparametric Wilcoxon rank sum test for median difference and 95% Hodges-Lehmann (HL) confidence intervals (CIs). The intraclass correlation coefficient (ICC) was used to assess the agreement between the assessors. RESULTS: A total of 210 patients from 8 centers were included, of whom 121 underwent MRI at TEA (75.6% of alive patients): 57 in the cerebral oximetry group and 64 in the usual care group. There was an excellent correlation between the assessors for the Kidokoro score (ICC agreement: 0.93, 95% CI: 0.91-0.95). The results showed no significant differences between the cerebral oximetry group (median 2, interquartile range [IQR]: 1-4) and the usual care group (median 3, IQR: 1-4; median difference -1 to 0, 95% HLCI: -1 to 0; p value 0.1196). CONCLUSIONS: In EPI, the use of cerebral oximetry-guided treatment did not lead to significant alterations in brain injury, as determined by MRI at TEA. The strong correlation between the assessors highlights the potential of the Kidokoro score in multicenter trials.

Neglected Populations Not to Be Forgotten: Tackling Antimicrobial Resistance in Neonatal Infections.

Making further progress in reducing child mortality hinges on lowering the annual count of neonatal deaths; currently, this stands at 2 [...].

Effects of Perinatal Antibiotic Exposure and Neonatal Gut Microbiota.

Antibiotic therapy is one of the most important strategies to treat bacterial infections. The overuse of antibiotics, especially in the perinatal period, is associated with long-lasting negative consequences such as the spread of antibiotic resistance and alterations in the composition and function of the gut microbiota, both of which negatively affect human health. In this review, we summarize recent evidence about the influence of antibiotic treatment on the neonatal gut microbiota and the subsequent negative effects on the health of the infant. We also analyze the possible microbiome-based approaches for the re-establishment of healthy microbiota in neonates.

Italian immunization calendar implementation: Time to optimize number of vaccination appointments?

In the Italian vaccination schedule, at least six vaccination appointments are scheduled in the first year of life. This implies more discomfort for both the patient and the parents. This was particularly evident during the COVID-19 pandemic, during which several appointments were missed. A UK experience with three injectable vaccines and an oral one co-administered at the same appointment (4-in-1) at 2 and 4 months of age showed interesting results. The vaccination coverage was high, consistent with previous practice, and no relevant increase in adverse events was reported. Translating the UK experience into the Italian context would not be immediate, due to several organizational and social issues. Nevertheless, this option warrants some further considerations, which are discussed in this manuscript.

The Management of Neonates ≥34 Weeks' Gestation at Risk of Early Onset Sepsis: A Pilot Study.

Early onset sepsis (EOS) is a potentially fatal condition in neonates, and its correct management is still challenging for neonatologists. Early antibiotic administration in the neonatal period may carry short- and long-term risks. Neonatal EOS calculator has been recently introduced as a new strategy to manage infants at risk of sepsis, and has shown promising results. METHODS: In this single-center observational retrospective study, 1000 neonates ≥ 34 weeks' gestation were enrolled with the aim to evaluate our standard protocol for the management of suspected EOS compared to the EOS calculator. Outcome measures included the following: (1) incidence of EOS and (2) proportion of infants in need of sepsis evaluations and antibiotics using our standard protocol versus theoretical application of EOS calculator. RESULTS: A total of 223/1000 infants underwent blood investigations versus 35/1000 (3.5%) if EOS calculator had been applied (p < 0.0001; k = 0.18). Furthermore, 48/1000 infants received antibiotics with our protocol versus 35/1000 with EOS calculator (p = 0.12; k = 0.58). Three infants had a positive blood culture that EOS calculator would have missed. CONCLUSIONS: In our study, EOS calculator could have reduced investigations but not antibiotic therapy. EOS calculator is an effective and promising tool, but further studies are required to improve it.

Pressure and tidal volume delivery in extremely preterm infants at birth using different t-piece resuscitation devices.

Infants <28 weeks' gestation in need of inflations at birth were recorded with Respiratory Function Monitor. Two devices were used for resuscitation. Peak Inspiratory Pressure spikes were visible in all inflations with GE Panda and in none with Neo-Puff. There was no significant difference in mean Vte/kg between GE Panda and Neo-Puff.

Tidal volume optimization and heart rate response during stabilization of very preterm infants.

AIM: To verify the added value of respiratory function monitor (RFM) to assess ventilation and the heart rate (HR) changes during stabilization of preterm infants. METHODS: Preterm infants <32 weeks' gestation, bradycardic at birth and in need for positive pressure ventilation (PPV) were included. The first 15 min of stabilization was monitored with RFM. Three time points were identified according to HR values (T0 the start of mask PPV; T1 the HR rise >100 bpm; T2 the delivery of the last PPV). For each inflation, PIP, PEEP, MAP, expired tidal volume/kg (Vte/kg), and mean dynamic compliance (Cdyn) were analyzed. RESULTS: PIP and MAP values were significantly higher at T1 (27.09 ± 5.37 and 17.47 ± 3.85 cmH2 O) and at T2 (24.7 ± 3.86 and 15.2 ± 3.78 cmH2 O) compared to T0 (24.05 ± 2.27 and 15.85 ± 2.77 cmH2 O). PEEP at T1 was significantly higher (6.27 ± 2.17 cmH2 O) compared to T2 (5.61 ± 1.50 cmH2 O). Vte/kg showed significantly lower T0 values (3.57 ± 2.14 ml/kg) compared to T1 (6.18 ± 2.51 ml/kg) and T2 (6.89 ± 2.40 ml/kg). There was a significant effect of time on Cdyn. CONCLUSIONS: A clear correspondence between HR rise and adequate Vte/kg during stabilization of very preterm infants was highlighted. RFM might be useful to tailor ventilation, following real-time changes of lung compliance.