Use of neonatal lung ultrasound in European neonatal units: a survey by the European Society of Paediatric Research.

OBJECTIVE: Regarding the use of lung ultrasound (LU) in neonatal intensive care units (NICUs) across Europe, to assess how widely it is used, for what indications and how its implementation might be improved. DESIGN AND INTERVENTION: International online survey. RESULTS: Replies were received from 560 NICUs in 24 countries between January and May 2023. LU uptake varied considerably (20%-98% of NICUs) between countries. In 428 units (76%), LU was used for clinical indications, while 34 units (6%) only used it for research purposes. One-third of units had <2 years of experience, and only 71 units (13%) had >5 years of experience. LU was mainly performed by neonatologists. LU was most frequently used to diagnose respiratory diseases (68%), to evaluate an infant experiencing acute clinical deterioration (53%) and to guide surfactant treatment (39%). The main pathologies diagnosed by LU were pleural effusion, pneumothorax, transient tachypnoea of the newborn and respiratory distress syndrome. The main barriers for implementation were lack of experience with technical aspects and/or image interpretation. Most units indicated that specific courses and an international guideline on neonatal LU could promote uptake of this technique. CONCLUSIONS: Although LU has been adopted in neonatal care in most European countries, the uptake is highly variable. The main indications are diagnosis of lung disease, evaluation of acute clinical deterioration and guidance of surfactant. Implementation may be improved by developing courses and publishing an international guideline.

Neonatal point-of-care lung ultrasound: what should be known and done out of the NICU?

Lung ultrasound is rapidly becoming a useful tool in the care of neonates: its ease of use, reproducibility, low cost, and negligible side effects make it a very suitable tool for the respiratory care of all neonates. This technique has been extensively studied by different approaches in neonatal intensive care unit (NICU), both for diagnostic and prognostic aims and to guide respiratory treatments. However, many neonates are being born in level I/II hospitals without NICU facilities so all pediatricians, not just neonatal intensivists, should be aware of its potential. This is made possible by the increasing access to ultrasound machines in a modern hospital setting. In this review, we describe the ultrasonographic characteristics of the normal neonatal lung. We also discuss the ultrasound features of main neonatal respiratory diseases: transient tachypnea of the neonate (TTN), respiratory distress syndrome (RDS), meconium aspiration syndrome (MAS), pneumothorax (PNX), pleural effusion (PE), or pneumonia. Finally, we mention two functional approaches to lung ultrasound: 1. The use of lung ultrasound in level I delivery centers as a mean to assess the severity of neonatal respiratory distress and request a transport to a higher degree structure in a timely fashion. 2. The prognostic accuracy of lung ultrasound for early and targeted surfactant replacement. CONCLUSION:  LU is still a useful tool in level I/II neonatal units, both for diagnostic and functional issues. WHAT IS KNOWN: • Neonatal lung ultrasound has been recently introduced in the usual care in many Neonatal Intensive Care Units. WHAT IS NEW: • It also has many advantages in level I/II neonatal units, both for neonatologist or even pediatricians that treat neonates in those sites.

Renal Function Impairment in Children With Congenital Cytomegalovirus Infection: A Cross-sectional Study.

BACKGROUND: We aimed to determine the prevalence and severity of glomerular and tubular renal dysfunction by means of urinalysis in infants and toddlers with congenital cytomegalovirus infection (cCMV) and their association with cCMV disease, viruria and antiviral treatment. METHODS: This cross-sectional study was done using the Spanish Registry of Congenital Cytomegalovirus Infection. First-morning urine samples were collected from January 2016 to December 2018 from patients <5 years old enrolled in Spanish Registry of Congenital Cytomegalovirus Infection. Samples were excluded in case of fever or other signs or symptoms consistent with acute infection, bacteriuria or bacterial growth in urine culture. Urinary protein/creatinine and albumin/creatinine ratios, urinary beta-2-microglobulin levels, hematuria and CMV viruria were determined. A 0.4 cutoff in the urinary albumin/protein ratio was used to define tubular (<0.4) or glomerular (>0.4) proteinuria. Signs and symptoms of cCMV at birth, the use of antivirals and cCMV-associated sequelae at last available follow-up were obtained from Spanish Registry of Congenital Cytomegalovirus Infection. RESULTS: Seventy-seven patients (37 females, 48.1%; median [interquartile range] age: 14.0 [4.4-36.2] months) were included. Symptom-free elevated urinary protein/creatinine and albumin/creatinine ratios were observed in 37.5% and 41.9% of patients, respectively, with tubular proteinuria prevailing (88.3%) over glomerular proteinuria (11.6%). Proteinuria in the nephrotic range was not observed in any patients. In multivariate analysis, female gender was the only risk factor for tubular proteinuria (adjusted odds ratio = 3.339, 95% confidence interval: 1.086-10.268; P = 0.035). cCMV disease at birth, long-term sequelae, viruria or the use of antivirals were not associated with urinalysis findings. CONCLUSIONS: Mild nonsymptomatic tubular proteinuria affects approximately 40% of infants and toddlers with mostly symptomatic cCMV in the first 5 years of life.

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.

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.

Imaging of bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a multifactorial disease with many associated co-morbidities, responsible for most cases of chronic lung disease in childhood. The use of imaging exams is pivotal for the clinical care of BPD and the identification of candidates for experimental therapies and a closer follow-up. Imaging is also useful to improve communication with the family and objectively evaluate the clinical evolution of the patient's disease. BPD imaging has been classically performed using only chest X-rays, but several modern techniques are currently available, such as lung ultrasound, thoracic tomography, magnetic resonance imaging and electrical impedance tomography. These techniques are more accurate and provide clinically meaningful information. We reviewed the most recent evidence published in the last five years regarding these techniques and analyzed their advantages and disadvantages.

The increase in diaphragm thickness in preterm infants is related to birth weight: a pilot study.

Diaphragm ultrasound (DU) has been used in adult and pediatric critical patients in relation to prediction of extubation success or to detect diaphragm dysfunction, but there is a lack of evidence in neonates. Our aim is to study the evolution of diaphragm thickness in preterm infants, as well as related variables. This prospective monocentric observational study included preterm infants born before 32 weeks (PT32). We performed DU to measure right and left inspiratory and expiratory thickness (RIT, LIT, RET, and LET) and calculated the diaphragm-thickening fraction (DTF) in the first 24 h of life and then weekly until 36 weeks postmenstrual age, death, or discharge. Using multilevel mixed-effect regression, we evaluated the influence of time since birth on diaphragm measurements, as well as bronchopulmonary dysplasia (BPD), birth weight (BW), and days of invasive mechanical ventilation (IMV). We included 107 infants, and we performed 519 DUs. All diaphragm thickness increased with time since birth, but the only additional variable that influenced this growth was BW: beta coefficients RIT = 0.00006; RET = 0.00005; LIT = 0.00005; and LET = 0.00004, p < 0.001. Right DTF values remained stable since birth but left DTF increased with time only in infants with BPD.   Conclusion: In our population we found that the higher the BW, the higher diaphragm thicknesses at birth and follow-up. Contrary to the previously published findings in adult and pediatric settings, we were unable to describe a relationship between days of IMV and diaphragm thickness in PT32. The final diagnosis of BPD does not influence this increase either, but it does increase left DTF. What is Known: • Diaphragm thickness and diaphragm thickening fraction have been related to the time on invasive mechanical ventilation in adults and pediatric patients, as well as with extubation failure. • Very few evidence is yet available on the use of diaphragmatic ultrasound in preterm infants. What is New: • Birth weight is the only variable related to diaphragm thickness in preterm infants born before 32 weeks postmenstrual age. • Days of invasive mechanical ventilation do not influence diaphragm increase in thickness in preterm infants.

Lung ultrasound description of a newborn with bronchial atresia: A case report.

Introduction: Congenital pulmonary malformations are a heterogeneous group of embryological alterations at different stages of lung development, the most frequent being the congenital malformation of the airway. Lung ultrasound is a very useful tool in neonatal intensive care units, providing great value for differential diagnosis, as well as therapeutic response or early detection of complications. Case Report: The case is a newborn of 38weeks' gestation who was followed by prenatal ultrasound control for suspected adenomatous cystic malformation type III in the left lung from week 22. She did not present complications during pregnancy. The study of Genetics and serological test were negative. She was born by urgent caesarean section due to breech presentation without requiring resuscitation, weighing 2.915 g. She was admitted to the Unit for study, remaining stable throughout her stay, with a normal physical examination. Atelectasis of the left upper lobe was appreciated by chest X-ray. Pulmonary ultrasound on the second day of life showed signs of consolidation in the left posterosuperior field with air bronchogram, without other alterations. In subsequent ultrasound controls, an interstitial infiltrate was observed in the left posterosuperior region, compatible with progressive aeration of the area, which was maintained until 1 month of life. The computed tomographic scan performed at 6months of age shows hyperlucency and increased volume in the left upper lobe with slight hypovascularization, accompanied by paramediastinal subsegmental atelectasis. There was a hypodense image at the hilar level. These findings were compatible with bronchial atresia, later confirmed by fiberoptic bronchoscopy. At 18months of age, surgical intervention was performed. Discussion and Conclusion: We present the first case of bronchial atresia diagnosed by LUS, thus adding new images to the very scarce literature currently available.

Lung Ultrasound Scores Progress Differently in Extreme and Very Preterm Infants after Birth: A Multicentre Prospective Study.

INTRODUCTION: The lung ultrasound score (LUS) has been suggested to predict moderate-severe bronchopulmonary dysplasia (msBPD) in preterm infants. We aimed to assess LUS evolution after birth in preterm infants and the effect of gestational age. METHODS: This multicentre prospective observational study was performed with newborns born before 33 weeks of gestation. We created two groups: group 1 (23-27 weeks) and group 2 (28-32 weeks). We compared LUSs between the groups from birth until 36 weeks of postmenstrual age, and we estimated the LUS evolution in each group with a linear multilevel mixed-effects regression model. The effects of the need for surfactant or an msBPD diagnosis were also studied. RESULTS: We included 339 patients: 122 (36%) in group 1 and 217 (64%) in group 2. The infants in group 1 showed a steady progression in the LUS from birth until 4 weeks of age and a subsequent decrease; the infants in group 2 showed a progressive decrease in the LUS throughout the study. This progression varied significantly in the first weeks of life in infants who required surfactant at birth and after the first week of life in the patients diagnosed with msBPD. DISCUSSION/CONCLUSIONS: Extremely preterm infants showed persistently high LUSs during the first weeks of life, regardless of the progression to msBPD. In this group, the infants who did not require surfactant at birth exhibited an increase in their LUSs after the first week until their values were equal to the remaining infants in their group.

Lung ultrasound score has better diagnostic ability than NT-proBNP to predict moderate-severe bronchopulmonary dysplasia.

The N-terminal end of B-type natriuretic peptide (NT-proBNP) and lung ultrasound (LUS) score have been proven to be adequate early biomarkers of bronchopulmonary dysplasia (BPD) in preterm infants. Our aim was to study if the predictive capacity of each one is increased by analyzing them together. We included infants born before 32 weeks with NT-proBNP and LUS scores on the first day of life (DOL) and on the 3rd, 7th, and 14th DOL and compared the diagnostic ability for moderate-severe BPD (msBPD) of each biomarker and in combination. We also compared them with a multivariate model of msBPD using only clinical variables. The sample size was 133 patients, and twenty-seven (20%) developed msBPD. The LUS score on the 7th DOL had better performance than NT-proBNP at the same moment: area under the receiver operating characteristic curve (AUC) 0.83 (0.75-0.89) versus 0.66 (0.56-0.75), p = 0.003, without differences in the rest of the times studied. These values did not increase when using the combination of both. A multivariate regression model that included only clinical variables (birth weight and invasive mechanical ventilation (IMV) at the 7th DOL) predicted msBPD with the same AUC as after the addition of any of these biomarkers, neither together. CONCLUSION: The LUS score is a better predictor of msBPD on the 7th DOL than NT-proBNP in preterm infants born before 32 weeks, although they have similar diagnostic accuracy on the 1st, 3rd, and 14th DOL. Neither of them, nor together, have a better AUC for msBPD than a clinical model with birthweight and the need for IMV at the 7th DOL. WHAT IS KNOWN: • NT-proBNP and LUS score are early predictors of moderate-severe bronchopulmonary dysplasia (msBPD). WHAT IS NEW: • The combination of both NT-proBNP and LUS score does not increase the predictive ability of each separately.

Ultrasound-guided vascular access in the neonatal intensive care unit: a nationwide survey.

Ultrasound-guided vascular access (USG-VA) is recommended by international practice guidelines but information regarding its use in the neonatal intensive care unit (NICU) is lacking. Our objective was to assess neonatologist's perceptions and current implementation of USG-VA in Spain. This was a nationwide online survey. The survey was composed of 37 questions divided in 4 domains: (1) neonatologist's background, (2) NICU characteristics, (3) personal perspectives about USG-VA, and (4) clinical experience in USG-VA. One-hundred and eighty survey responses from 59 NICUs (62% of Spanish NICUs) were analyzed. Most neonatologists (81%) perceive that competence in USG-VA is indispensable or very useful in clinical practice. However, 64 (35.5%) have never used USG-VA in real patients. Among neonatologists with some experience in USG-VA most perform less than 5 procedures per year (59% in venous access and 80% in arterial access) and a 38% and 60% have never used USG for venous and arterial access, respectively, in very low birth weight infants (VLBWI). More than a half of neonatologists (55.5%) use US to check catheter tip location but a 46.6% always perform a radiography for confirmation. Spanish neonatologists report that resident/fellow training in USG-VA is absent (52.2%) or unstructured (32%) in their units. The lack of adequate training is identified by a 60% of neonatologists as the most important barrier for implementation of USG-VA and 87% would recommend that future neonatologists receive formal training. CONCLUSION: Spanish neonatologists perceive that USG-VA is important in clinical practice but currently, these techniques are largely underused. Our results indicate that specific training in USG-VA should be implemented in the NICU. WHAT IS KNOWN: • Ultrasound-guided vascular access is recommended as the preferred method for central venous access and arterial line placement in children and adults. • The degree of current implementation of ultrasound for vascular access in the NICU and the perceptions of neonatologist about its use are largely unknown. WHAT IS NEW: • Most neonatologists consider that competence in ultrasound-guided vascular access is an indispensable aid for clinical practice. • However, most neonatologists are not adequately trained in ultrasound-guided vascular access and the technique is largely underused.

Utilidad de la ecografía pulmonar en el diagnóstico y seguimiento de la patología respiratoria neonatal / Usefulness of lung ultrasound in the diagnosis and follow-up of respiratory diseases in neonates

Objetivo: La ecografía pulmonar es una herramienta útil para el diagnóstico y seguimiento de la patología del paciente crítico neonatal. Su uso está cada vez más extendido gracias a sus ventajas sobre otras pruebas de imagen y el rápido incremento en la evidencia científica a su favor, constituyendo así, un pilar básico de las guías «point of care ultrasound» (POCUS) neonatal. El objetivo de este artículo especial es proporcionar las bases y aplicaciones diagnóstico-terapéuticas establecidas de la ecografía pulmonar, y dar a conocer nuevas aplicaciones. Métodos y resultados: La sección de ecografía pulmonar del Grupo de Trabajo de Ecografía Neonatal de la Sociedad Española de Neonatología resume la evidencia científica actual. Se describen los patrones ecográficos de las principales patologías respiratorias, aborda algunas de sus aplicaciones en la asistencia neonatal (predicción de ingreso, necesidad de surfactante, procedimientos ecoguiados, seguimiento del desarrollo pulmonar en el prematuro, entre otros) y propone su incorporación en otros escenarios actualmente menos establecidos como la reanimación o el manejo ventilatorio. Este artículo reafirma los beneficios de esta herramienta para ayudar en el diagnóstico, toma de decisiones terapéuticas, apoyo en procedimientos y valoración pronóstica. Conclusiones: La ecografía pulmonar debe establecerse como la prueba diagnóstica de elección en la patología respiratoria neonatal. Por ello, su entrenamiento debería formar parte de la formación de los neonatólogos e incluirse en los protocolos diagnóstico-terapéuticos asistenciales. Se deben seguir desarrollando líneas de investigación con estudios sólidos y multicéntricos que aumenten la calidad de la evidencia científica. (AU)

Objective: Lung ultrasound is a useful tool for diagnosis and follow-up of diseases in critically ill neonates. Its use is increasingly widespread thanks to its advantages over other imaging tests and the rapidly growing body of evidence to support it, and «point-of-care ultrasound» (POCUS) has become a key component in neonatal guidelines. The objective of this special article is to present the foundations and the established diagnostic and therapeutic applications of lung ultrasonography as well as introducing new applications. Methods and results: The Lung Ultrasound Section of the Neonatal Ultrasonography Working Group of the Spanish Neonatology Society has summarised the current scientific evidence. The article describes the sonographic features of the most common respiratory diseases, discusses some of the applications of ultrasound in neonatal care (such as prediction of admission and need of surfactant, ultrasound-guided procedures or monitoring of lung development in premature infants) and proposes its introduction in other scenarios in which its use is not quite established at present, such as resuscitation or respiratory management. This article reaffirms the usefulness of lung ultrasound in guiding diagnosis, clinical decision-making and prognosis and facilitating procedures. Conclusions: Lung ultrasound should be established as the gold standard for diagnosis of respiratory diseases in neonates. Therefore, training in lung ultrasound should be included in the educational curriculum of neonatologists and in diagnostic and therapeutic care protocols. Research on the subject should continue to be pursued with performance of rigorous multicentre studies to increase the quality of the evidence. (AU)

Meta-Analysis of Lung Ultrasound Scores for Early Prediction of Bronchopulmonary Dysplasia.

Rationale: Lung ultrasound scores (LUS) might be useful in monitoring neonates with chronic pulmonary insufficiency of prematurity and in predicting bronchopulmonary dysplasia (BPD). Given their ease of use, accuracy, and lack of invasiveness, LUS have been the subject of several recent studies. Objectives: We sought to clarify whether LUS provide an accurate and early (within the first 2 wk of life) prediction of BPD in preterm infants of gestational age ⩽32 weeks. Methods: This was a systematic review and diagnostic accuracy meta-analysis following PRISMA-P (Preferred Reporting Items for Systematic review and Meta-Analysis Protocols), PRISMA (Preferred Reporting Items for Systematic review and Meta-Analysis), and QUADAS (QUAlity of Diagnostic Accuracy Studies) guidelines. Studies designed to predict BPD in the first 2 weeks of life using LUS were selected. A classical LUS (calculated for 6 chest areas) and its extended version (eLUS, 10 chest areas) were tested. Results: Seven studies (1,027 neonates) were meta-analyzed. LUS and eLUS showed good diagnostic accuracy in predicting BPD at 7 and 14 days of life (area under the curve, 0.85-0.87; pooled sensitivity, 70-80%; pooled specificity, 80-87%). The diagnostic accuracy of LUS and eLUS did not differ at any time point (area under the curve difference always P > 0.05). Repeating the analyses without outliers or with moderate to severe BPD as the outcome yielded similar results. Meta-regressions showed that prenatal steroid prophylaxis and sex were not significant effect confounders. Conclusions: LUS are accurate for early prediction of BPD and moderate to severe BPD, in an average population of preterm infants ⩽32 weeks' gestation. The diagnostic accuracy is similar for LUS and eLUS, so the use of the simpler score should be advocated. Registration: PROSPERO CRD42021233010.