A narrative review on tip navigation and tip location of central venous access devices in the neonate: Intracavitary ECG or real time ultrasound?

The proper location of the tip of a central venous access device plays a crucial role in minimizing the risks potentially associated with its use. Recent guidelines strongly recommend preferring real-time, intra-procedural methods of tip location since they are more accurate, more reliable and more cost-effective than post-procedural methods. Intracavitary electrocardiography and real time ultrasound can both be applied in the neonatal setting, but they offer different advantages or disadvantages depending on the type of central venous access device. Reviewing the evidence currently available about the use of these two methods in neonates, in terms of applicability, feasibility and accuracy, it can be concluded that (a) real time ultrasound is the only acceptable methodology for tip navigation for any central venous access device in neonates, (b) intracavitary electrocardiography is the preferred method of tip location for central catheters inserted by ultrasound-guided cannulation of the internal jugular vein or the brachiocephalic vein, and (c) real time ultrasound is the preferred method of tip location for umbilical venous catheters, epicutaneo-cava catheters, and central catheters inserted by ultrasound-guided cannulation of the common femoral vein.

Patent ductus arteriosus (also non-hemodynamically significant) correlates with poor outcomes in very low birth weight infants. A multicenter cohort study.

OBJECTIVES: To standardize the diagnosis of patent ductus arteriosus (PDA) and report its association with adverse neonatal outcomes in very low birth weight infants (VLBW, birth weight < 1500 g). STUDY DESIGN: A multicenter prospective observational study was conducted in Emilia Romagna from March 2018 to October 2019. The association between ultrasound grading of PDA and adverse neonatal outcomes was evaluated after correction for gestational age. A diagnosis of hemodynamically significant PDA (hsPDA) was established when the PDA diameter was ≥ 1.6 mm at the pulmonary end with growing or pulsatile flow pattern, and at least 2 of 3 indexes of pulmonary overcirculation and/or systemic hypoperfusion were present. RESULTS: 218 VLBW infants were included. Among infants treated for PDA closure in the first postnatal week, up to 40% did not have hsPDA on ultrasound, but experienced clinical worsening. The risk of death was 15 times higher among neonates with non-hemodynamically significant PDA (non-hsPDA) compared to neonates with no PDA. In contrast, the risk of death was similar between neonates with hsPDA and neonates with no PDA. The occurrence of BPD was 6-fold higher among neonates with hsPDA, with no apparent beneficial role of early treatment for PDA closure. The risk of IVH (grade ≥ 3) and ROP (grade ≥ 3) increased by 8.7-fold and 18-fold, respectively, when both systemic hypoperfusion and pulmonary overcirculation were present in hsPDA. CONCLUSIONS: The increased risk of mortality in neonates with non-hsPDA underscores the potential inadequacy of criteria for defining hsPDA within the first 3 postnatal days (as they may be adversely affected by other clinically severe factors, i.e. persistent pulmonary hypertension and mechanical ventilation). Parameters such as length, diameter, and morphology may serve as more suitable ultrasound indicators during this period, to be combined with clinical data for individualized management. Additionally, BPD, IVH (grade ≥ 3) and ROP (grade ≥ 3) are associated with hsPDA. The existence of an optimal timeframe for closing PDA to minimize these adverse neonatal outcomes remains uncertain.

Prospective case series study on the use of a novel analgosedation protocol for ultrasound-guided catheterization in Neonatal Intensive Care Unit.

Critically ill newborns admitted to Neonatal Intensive Care Unit often require a centrally inserted central catheters (CICCs) inserted by ultrasound-guided puncture of the internal jugular or brachio-cephalic vein. Achieving an appropriate level of sedation and analgesia is paramount for procedure success and patient safety, avoiding the potential risks associated with excessive deep sedation. The aim of this study is to evaluate the feasibility of a novel protocol of sedation. Data from 46 patients were prospectively collected. The feasibility was assessed throughout the monitoring of adverse events and the incidence of spontaneous movements. The procedure was completed in 100% of cases. There were no cases of escalation of the baseline ventilatory support despite the procedure and no case of hypotension, and all spontaneous movements were controlled with additional boluses when required. CONCLUSION: Our study represents the very first step towards the design of a validated protocol for analgosedation during ultrasound-guided CICC insertion in NICU. WHAT IS KNOWN: • Critically ill newborns admitted to Neonatal Intensive Care Unit often require a centrally inserted central catheter. • Achieving an appropriate level of sedation and analgesia is paramount for procedure success and patient safety, avoiding the potential risks associated with excessive deep sedation. WHAT IS NEW: • The use of this new protocol for analgosedation is able to achieve a good level of sedation and pain control without significant adverse event. • Ultrasound-guided CICC insertion can be performed even in non-ventilated newborns.

A novel neonatal protocol for Safe Insertion of Umbilical Venous Catheters (SIUVeC): Minimizing complications in placement and management.

Insertion of umbilical venous catheters is a common procedure in neonatal intensive care. Though sometimes lifesaving, this maneuver is potentially associated with early and late complications, some of which may be severe and even life threatening (catheter malposition, hepatic lesions, venous thrombosis, pericardial effusion, etc.). The recent literature suggests several operative strategies that, if adopted systematically, may significantly reduce the incidence of both early and late catheter related complications. This paper describes a standardized protocol (Safe Insertion Umbilical Venous Catheter = SIUVeC) which incorporates such novel strategies, with the goal of minimizing the complications related to this procedure.

Lung UltrasouNd Guided surfactant therapy in preterm infants: an international multicenter randomized control trial (LUNG study).

BACKGROUND: The management of respiratory distress syndrome (RDS) in premature newborns is based on different types of non-invasive respiratory support and on surfactant replacement therapy (SRT) to avoid mechanical ventilation as it may eventually result in lung damage. European guidelines currently recommend SRT only when the fraction of inspired oxygen (FiO2) exceeds 0.30. The literature describes that early SRT decreases the risk of bronchopulmonary dysplasia (BPD) and mortality. Lung ultrasound score (LUS) in preterm infants affected by RDS has proven to be able to predict the need for SRT and different single-center studies have shown that LUS may increase the proportion of infants that received early SRT. Therefore, the aim of this study is to determine if the use of LUS as a decision tool for SRT in preterm infants affected by RDS allows for the reduction of the incidence of BPD or death in the study group. METHODS/DESIGN: In this study, 668 spontaneously-breathing preterm infants, born at 25+0 to 29+6 weeks' gestation, in nasal continuous positive airway pressure (nCPAP) will be randomized to receive SRT only when the FiO2 cut-off exceeds 0.3 (control group) or if the LUS score is higher than 8 or the FiO2 requirements exceed 0.3 (study group) (334 infants per arm). The primary outcome will be the difference in proportion of infants with BPD or death in the study group managed compared to the control group. DISCUSSION: Based on previous published studies, it seems that LUS may decrease the time to administer surfactant therapy. It is known that early surfactant administration decreases BPD and mortality. Therefore, there is rationale for hypothesizing a reduction in BPD or death in the group of patients in which the decision to administer exogenous surfactant is based on lung ultrasound scores. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT05198375 . Registered on 20 January 2022.

The Role of Ultrasound in Epicutaneo-Caval Catheter Insertion in Neonates: Systematic Review, Meta-Analysis and Future Perspectives.

Chest and abdominal X-rays after the insertion of an epicutaneo-caval catheter in infants are the standard method of checking the tip location in many neonatal intensive care units. The role of ultrasound in the tip location of the epicutaneo-caval catheter in neonates has been the subject of many recent studies. This systematic review investigates the accuracy of epicutaneo-caval catheter tip location by comparing ultrasound and conventional radiology. We performed a systematic literature search in multiple databases. The selection of studies yielded nineteen articles. The systematic review and meta-analysis were performed according to PRISMA (Preferred Reporting Items for Systematic reviews and Meta-analysis). The analyses showed that ultrasound is a better imaging technique for epicutaneo-caval catheter tip location in the neonatal intensive care unit than conventional radiology. By improving operator training and selecting a standardized echography protocol, ultrasound could become the gold standard for visualizing the epicutaneo-caval catheter tip in the neonatal intensive care unit. This would have some important benefits: (1) increased accuracy in tip location (2); a more rapid use of the central venous access (3); and a significant reduction in radiation exposure.

The neonatal DAV-expert algorithm: a GAVeCeLT/GAVePed consensus for the choice of the most appropriate venous access in newborns.

In most NICUs, the choice of the venous access device currently relies upon the operator's experience and preferences. However, considering the high failure rate of vascular devices in the neonatal population, such clinical choice has a critical relevance and should preferably be based on the best available evidence. Though some algorithms have been published over the last 5 years, none of them seems in line with the current scientific evidence. Thus, the GAVePed-which is the pediatric interest group of the most important Italian group on venous access, GAVeCeLT-has developed a national consensus about the choice of the venous access device in the neonatal population. After a systematic review of the available evidence, the panel of the consensus (which included Italian neonatologists specifically experts in this area) has provided structured recommendations answering four sets of questions regarding (1) umbilical venous catheters, (2) peripheral cannulas, (3) epicutaneo-cava catheters, and (4) ultrasound-guided centrally and femorally inserted central catheters. Only statements reaching a complete agreement were included in the final recommendations. All recommendations were also structured as a simple visual algorithm, so as to be easily translated into clinical practice.  Conclusion: The goal of the present consensus is to offer a systematic set of recommendations on the choice of the most appropriate vascular access device in Neonatal Intensive Care Unit.

Use of the Dialkylcarbamoylchloride Dressing in the Care of Central Venous Access Exit Site in a Pediatric and Neonatal Population.

Dialkylcarbamoylchloride dressing is a fatty acid derivative that has been shown in vitro to bind a number of pathogenic microorganisms. The purpose of this prospective study was to evaluate the safety and the efficacy of this technology in the care of the exit site of central venous catheter in a paediatric and neonatal population. METHODS: The study was conducted from September 2020 to December 2022 at the Infermi Hospital in Rimini. Central venous catheters were placed using the SIC bundle for insertion. Dialkylcarbamoylchloride dressing was placed below the subcutaneous anchoring at the time of CVC placement and at each dressing change. Data about the catheters and the exit site were recorded and then compared with an historical cohort. RESULTS: 118 catheters were placed during the studied period. The dialkylcarbamoylchloride dressing was well-tolerated. No case of systemic or local infection was recorded. The comparison with the historical cohort showed a reduction in the rate of exit site infection (p value 0.03). CONCLUSION: Dialkylcarbamoylchloride dressing is well-tolerated in paediatric and neonatal population. It represents a promising tool as a strategy for infection prevention.

The intracavitary ECG method for tip location of ultrasound-guided centrally inserted central catheter in neonates.

BACKGROUND: The correct position of the tip of a central venous access device is important in all patients, and especially in neonates. The traditional method of tip location (approximated intra-procedural length estimation + post procedural chest X-ray) is currently considered inaccurate and not cost-effective by most recent guidelines, which recommend the adoption of tip location by intracavitary electrocardiography (IC-ECG) whenever possible. METHODS: This study prospectively investigated the applicability, the feasibility, the accuracy, and the safety IC-ECG for tip location in neonates requiring insertion of ultrasound-guided centrally inserted central venous catheters (CICCs) with caliber 3Fr or more. All catheter tip locations were verified using simultaneously both IC-ECG and ultrasound-based tip location, using the Neo-ECHOTIP protocol. RESULTS: A total of 105 neonates were enrolled. The applicability of IC-ECG was 100% since a P wave was evident on the surface ECG of all neonates recruited for the study. The feasibility was also 100% since an increase of the P-wave was detected in all cases. The accuracy was also 100%, since a perfect match between IC-ECG based tip location and ultrasound-based tip location was found. There were no adverse events directly or indirectly related to the IC-ECG technique; no arrhythmias occurred. CONCLUSIONS: When applied to ultrasound guided CICCs, tip location by IC-ECG is applicable and feasible in neonates, and it is safe and accurate.

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.

Amplitude-integrated EEG recorded at 32 weeks postconceptional age. Correlation with MRI at term.

OBJECTIVE: The study aims to establish the role of late aEEG (scored by Burdjalov) in predicting brain maturation as well as abnormalities evaluated at term equivalent age (TEA) by brain MRI. METHODS: 91 infants born before 30 wks gestation underwent an aEEG monitoring at 32 wks postconceptional age (PCA). aEEG, was correlated with TEA MRI, scored by Kidokoro. RESULTS: A significant correlation between the aEEG score and the MRI scores was found. The same results were obtained for the aEEG continuity score; cyclicity and bandwidth scores were associated with grey matter and cerebellar MRI items. Moreover, a correlation between aEEG and cEEG recorded both at 32 and 40 wks PCA, was found. CONCLUSIONS: aEEG monitoring can be predictive of MRI findings at TEA, suggesting that it could be implemented as a useful tool to support ultrasound to help identify neonates who will benefit from early intervention services.

Neuroprem 2: An Italian Study of Neurodevelopmental Outcomes of Very Low Birth Weight Infants.

Background: Despite the increased survival of preterm newborns worldwide, the risk of neurodevelopmental disabilities remains high. Analyzing the outcomes of the preterm population can identify risk factors and enable specific early interventions. Aims: Neuroprem is a prospective cohort study of very low birth weight (VLBW) infants that aims to evaluate the neurodevelopmental outcomes and risk factors for severe functional disability at 2 years of corrected age. Methods: Nine Italian neonatal intensive care units participated in the network. The Griffiths Mental Developmental Scales (GMDS-R) or the Bayley Scales of Infant and Toddler Development (BSDI III) and a neuro-functional evaluation (according to the International Classification of Disability and Health and Neuro-Functional Assessment, or NFA ICF-CY) were administered to VLBW infants at 24 months of corrected age. The primary outcome measure was severe functional disability, defined as cerebral palsy, bilateral blindness, deafness, an NFA ICF-CY of >2, a BSDI III cognitive composite score of <2 SD, or a GMDS-R global quotient score of <2 SD. Perinatal risk factors for severe functional disability were assessed through multivariate logistic regression analysis. Results: Among 502 VLBW survivors who completed the 24-month follow-up, 48 (9.6%) presented severe functional disability, of whom 27 had cerebral palsy (5.4%). Rates of severe functional disability and cerebral palsy were higher in neonates with a lower gestational age (p < 0.001). Overall, 147 infants (29.3%) were referred to neuromotor intervention. In the multivariate regression model, gestational age at birth OR 0.79; 95% CI 0.67-0.90; p = 0.001) and periventricular-intraventricular hemorrhage (OR 2.51; 95% CI 1.19-5.26; p = 0.015) were significantly associated with severe functional disability. Conclusion: Neuroprem 2 provides updated information on the neurodevelopmental outcomes of VLBW infants in a large Italian cohort. The overall rate of neurodevelopmental disabilities was quite lower than reported in the previous literature. These data indicate the need for structured follow-up programs from a national neonatal network perspective.

Being the Father of a Preterm-Born Child: Contemporary Research and Recommendations for NICU Staff.

Background: Most studies on parental reactions to a preterm birth and to hospitalization of the newborn in Neonatal Intensive Care Units (NICUs) have involved mothers. However, emotional responses and behaviors of fathers are equally important. Usually, the father is the first to meet the preterm newborn, to find out information about baby's condition and to communicate to the mother and other family members. In this context he is often left alone and can show psychological difficulties including affective disorders such as depression or anxiety. This paper describes the role of fathers in the NICU, the best practices to support fathers, and to explain the role of a psychologist in the NICU staff. Considerations and suggestions are provided on the difficulties encountered to support parents, with a focus on the role of fathers during the COVID-19 pandemic. Methods and Discussion: Considering contemporary research data and following an attachment perspective, we analyze the role of the father of a preterm-born child in the relation with the partner and in newborn caring. Research has shown that involving fathers in newborn care in NICU and at home is essential not only because it promotes the father/son attachment relationship and has positive effects on the psychological and somatic development of the newborn, but also for the health of the mother and whole family. Conclusion: Recommendations are provided to enhance the functions of fathers in the NICU, promote their involvement in the care of their infant, and interventions to prevent the manifestation of psychological suffering and/or perinatal affective disorders. The commitments of a psychologist in a NICU team are presented and require not only clinical skills, but also the ability to manage the emotional and relational difficulties of fathers, family and NICU staff. Considerations and suggestions are provided on the difficulties encountered by parents in the NICU during the COVID-19 pandemic.

Centrally inserted central catheters in preterm neonates with weight below 1500 g by ultrasound-guided access to the brachio-cephalic vein.

OBJECTIVE: Central venous access in critically ill newborns can be challenging. Ultrasound-guided brachio-cephalic vein catheterization is a relatively new procedure, recently introduced in several neonatal intensive care units. The aim of this study is to evaluate the safety and feasibility of such a technique in preterm babies. DESIGN: Retrospective analysis of prospectively collected data on ultrasound-guided central venous catheter insertion in preterm neonates. SETTING: Neonatal intensive care unit. PATIENTS: Critically ill preterm neonates with weight below 1500 g requiring a central access. INTERVENTIONS: Ultrasound-guided brachio-cephalic vein catheterization. MAIN RESULTS: Thirty centrally inserted catheters were placed in 30 neonates. The success rate of the procedure was 100%. No case of accidental arterial or pleural puncture was registered during the study period. CONCLUSION: The brachio-cephalic vein can be safely catheterized in preterm newborns requiring intensive care after appropriate training.

Intrapartum Asphyxiated Newborns Without Fetal Heart Rate and Cord Blood Gases Abnormalities: Two Case Reports of Shoulder Dystocia to Reflect Upon.

Our report covers two cases of severe hypoxic-ischemic encephalopathy in newborns whose birth was complicated by shoulder dystocia. In both cases, there were inconsistencies observed among cardiotocographic traces, baby's clinical conditions at birth, and umbilical cord blood gases. Namely, normal cardiotocographic monitoring and cord pH > 7, in spite of the fact that the newborns were severely depressed at birth and their blood gases evaluated within 1 h from birth showed a severe metabolic acidosis. Moreover, one of the two newborns displayed moderately low hemoglobin levels. Metabolic and infectious causes were ruled out. Both newborns developed severe hypoxic-ischemic encephalopathy and received therapeutic hypothermia for 72 h. Both survived, one with a severe dystonic cerebral palsy whereas the other developed only a mild developmental delay in language. Cardiac asystole theory could explain these two cases, reinforcing the need for specific resuscitation guidelines for infants experiencing a birth complicated by shoulder dystocia.

An Uninfected Preterm Newborn Inadvertently Fed SARS-CoV-2-Positive Breast Milk.

There are increasing concerns regarding coronavirus disease, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Approaches to breastfeeding and the management of neonates born to pauci-symptomatic mothers with coronavirus disease vary worldwide, although some scientific societies across Europe and the United States have emphasized the benefits of breastfeeding, even with expressed breast milk. Because SARS-CoV-2 has been, thus far, only exceptionally detected in breast milk, the risk of disease transmission has remained hypothetical.We herein report the case of a healthy preterm newborn who was inadvertently fed SARS-CoV-2-positive breast milk. Two different samples, collected with and without strict hygiene precautions, were both confirmed to be SARS-CoV-2 positive. However, the newborn was not infected, supporting the protective role of breast milk. Furthermore, in this report, we highlight the difficulties in the practical management of a neonate whose breastfeeding mother was confirmed as positive for SARS-CoV-2 after delivery.

COnsensus on Pediatric Pain in the Emergency Room: the COPPER project, issued by 17 Italian scientific societies.

In the pediatric setting, management of pain in the emergency department - and even in common care - is a challenging exercise, due to the complexity of the pediatric patient, poor specific training of many physicians, and scant resources.A joint effort of several Italian societies involved in pediatrics or in pain management has led to the definition of the PIPER group and the COPPER project. By applying a modified Delphi method, the COPPER project resulted in the definition of 10 fundamental statements. These may represent the basis for improving the correct management of children pain in the emergency department.

Parechovirus infection causing sepsis-like illness in newborns: a NICU approach.

Human parechovirus (HpeV) is an important emerging infection in young infants, able to cause sepsis-like disease and meningoencephalitis, especially in newborns. Among the 19 identified genotypes, HPeV1, 3 and 6 are the most common types involved in human infections; HPeV3 is the type mainly responsible for neonatal infections and for infections involving the central nervous system. Signs and symptoms overlap with those of a bacterial infection and patients are usually treated with broad spectrum antibiotics. In the majority of cases lumbar puncture shows absence of pleocytosis, even in the presence of signs of meningitis. In these cases, cerebrospinal fluid cultures are negative for bacteria but, in the absence of diagnosis of viral infection, a full and unnecessary antibiotic cycle is often continued. Moreover, high sensitivity neuroimaging, i.e., magnetic resonance, and follow-up are often missed, thus resulting in substandard care. Availability of a real time PCR assay for HPeV RNA allows rapid and sensitive diagnosis as long as the disease is suspected. In this case study, we present cases of HPeV infections in newborns requiring neonatal intensive care admission, discuss their optimal management, and highlight the most relevant findings in the literature.

Neurodevelopmental Trajectories of Preterm Infants of Italian Native-Born and Migrant Mothers and Role of Neonatal Feeding.

There is evidence that preterm infants of migrant mothers are at a higher risk of adverse perinatal outcomes than those of native-born mothers, and that human milk feeding is beneficial to infants' neurodevelopment. Using the United Nations Human Development Index (HDI) to classify mother's country of origin, we investigated whether type of neonatal feeding (human milk vs. mixed milk vs. exclusive formula milk) affected preterm newborn neurodevelopment varying across different HDI categories (Italian native-born vs. high HDI migrant vs. low HDI migrant) up to 2 years of age. Neurodevelopment of 530 infants born in Italy at ≤32 weeks of gestational age and/or weighing <1500 g was measured at 3-, 6-, 9-, 12-, 18-, and 24-months corrected age (CA) using the revised Griffiths Mental Development Scale 0-2 years. The trajectories of the general developmental quotient and its five subscales were estimated using mixed models. At 24-months CA only preterm infants of low HDI migrant mothers and fed exclusive formula milk showed moderate neurodevelopment impairment, with lower developmental trajectories of eye-hand coordination, performance, and personal-social abilities. Migrant mothers from low HDI countries and their preterm infants should be targeted by specific programs supporting maternal environment, infant development, and human or mixed milk neonatal feeding. Future research should focus on a deeper understanding of the mechanisms through which type of feeding and mother migrant conditions interact in influencing preterm infants' neurodevelopment.

Mitophagy in Cardiovascular Diseases.

Cardiovascular diseases are one of the leading causes of death. Increasing evidence has shown that pharmacological or genetic targeting of mitochondria can ameliorate each stage of these pathologies, which are strongly associated with mitochondrial dysfunction. Removal of inefficient and dysfunctional mitochondria through the process of mitophagy has been reported to be essential for meeting the energetic requirements and maintaining the biochemical homeostasis of cells. This process is useful for counteracting the negative phenotypic changes that occur during cardiovascular diseases, and understanding the molecular players involved might be crucial for the development of potential therapies. Here, we summarize the current knowledge on mitophagy (and autophagy) mechanisms in the context of heart disease with an important focus on atherosclerosis, ischemic heart disease, cardiomyopathies, heart failure, hypertension, arrhythmia, congenital heart disease and peripheral vascular disease. We aim to provide a complete background on the mechanisms of action of this mitochondrial quality control process in cardiology and in cardiac surgery by also reviewing studies on the use of known compounds able to modulate mitophagy for cardioprotective purposes.