Can lung ultrasound score accurately predict surfactant replacement? A systematic review and meta-analysis of diagnostic test studies.

BACKGROUND: Clinical and radiographic criteria are traditionally used to determine the need for surfactant therapy in preterm infants. Lung ultrasound is a bedside test that offers a rapid, radiation-free, alternative to this approach. OBJECTIVE: To conduct a systematic review and meta-analysis to determine the accuracy of a lung ultrasound score (LUS) in identifying infants who would receive at least one surfactant dose. Secondary aims were to evaluate the predictive accuracy for ≥2 doses and the accuracy of a different image classification system based on three lung ultrasound profiles. METHODS: PubMed, SCOPUS, Biomed Central, and the Cochrane library between January 2011 and December 2021 were searched. Full articles enrolling preterm neonates who underwent lung ultrasound to predict surfactant administration were assessed and analyzed following Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) and QUADAS-2 guidelines. RESULTS: Seven prospective studies recruiting 697 infants met the inclusion criteria. Risk of bias was generally low. Oxygen requirement, clinical and radiographic signs of respiratory distress syndrome were used as reference standards for surfactant replacement. The summary receiver operator characteristic (sROC) curve for LUS predicting first surfactant dose showed an area under the curve (AUC) = 0.88 (95% confidence interval [CI]: 0.82-0.91); optimal specificity and sensitivity (Youden index) were 0.83 and 0.81 respectively. Pooled estimates of sensitivity, specificity, diagnostic odds ratio, negative predictive value, and positive predictive value for LUS predicting the first surfactant dose were 0.89 (0.82-0.95), 0.86 (0.78-0.95), 3.78 (3.05-4.50), 0.92 (0.87-0.97), 0.79 (0.65-0.92). The sROC curve for the accuracy of Type 1 lung profile in predicting first surfactant dose showed an AUC of 0.88; optimal specificity and sensitivity were both 0.86. Two studies addressing the predictive accuracy of LUS for ≥2 surfactant doses had high heterogeneity and were unsuitable to combine in a meta-analysis. DISCUSSION: Despite current significant variation in LUS thresholds, lung ultrasound is highly predictive of the need for early surfactant replacement. This evidence was derived from studies with homogeneous patient characteristics and low risk of bias.

Lung ultrasound in Italian neonatal intensive care units: A national survey.

INTRODUCTION: Lung ultrasound (LU) is a noninvasive, bedside imaging technique that is attracting growing interest in the evaluation of neonatal respiratory diseases. We conducted a nationwide survey of LU usage in Italian neonatal intensive care units (NICUs). METHODS: A structured questionnaire was developed and sent online to 114 Italian NICUs from June to September 2021. RESULTS: The response rate was 79%. In the past 4 years (range: 2-6), LU has been adopted in 82% of Italian NICUs. It is the first-choice diagnostic test in 23% of the centers surveyed. The main LU diagnostic applications reported were: pneumothorax (95%), respiratory distress syndrome (89%), transient tachypnea of the newborn (89%), plural effusion (88%), atelectasis (66%), pneumonia (64%), bronchopulmonary dysplasia (43%), congenital pulmonary airway malformation (41%), and congenital diaphragmatic hernia (34%). Thirty percent of participating centers calculated LU score routinely, but only seven units used it to predict the need for surfactant replacement. Sixty-six percent of respondents learned the LU technique via a self-training process, while 34% of them visited an expert in the field for one-to-one tuition. CONCLUSIONS: LU has a widespread use in Italian NICUs. However, the use of LU is extremely heterogeneous among centers. There is an urgent need to ensure standardization of clinical practice guidelines and to design and implement a formalized and accredited training program.

Lung ultrasound scores in neonatal clinical practice: A narrative review of the literature.

Lung ultrasound (LU) has in recent years increasingly been used as a point-of-care method. Initially, LU was used as a so-called descriptive diagnostic method for neonatal respiratory diseases. Instead, this review article focuses on the use of LU as a "functional" tool using classification of findings in patterns or using semiquantitative scores. We review and describe the evidence that led to the implementation of LU in predicting the need for surfactant replacement therapy in preterm infants and in the identification of newborns at risk of developing bronchopulmonary dysplasia. LU appears to be a very promising method for the future of clinical management of newborns in both acute and chronic phases of pulmonary pathologies related to prematurity. However, further studies are needed to define its role before full implementation.

Can lung ultrasound score accurately predict the need for surfactant replacement in preterm neonates? A systematic review and meta-analysis protocol.

Respiratory distress syndrome (RDS) is a leading cause of morbidity and mortality in preterm infants due to primary surfactant deficiency. Surfactant replacement has greatly improved the short and long term prognosis of RDS but its administration criteria remain uncertain. Lung ultrasound has been recently shown as a non-invasive, repeatable, bedside tool to estimate parenchymal aeration using a semiquantitative score (LUS). The objective of this systematic review and meta-analysis is to evaluate the accuracy of LUS, assessed on the first day of life, to predict surfactant replacement. Methods will follow the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines and the protocol has been registered in PROSPERO database (registration number: CRD42021247888). Primary outcome: in a population of preterm infants, LUS will be compared in neonates who received surfactant replacement versus those who did not. Secondary outcome will be the accuracy of lung ultrasound score to predict the need for ≥ 2 doses of surfactant.

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

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

Lung Ultrasound Score Progress in Neonatal Respiratory Distress Syndrome.

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

Point-of-care lung ultrasound in neonatology: classification into descriptive and functional applications.

Lung ultrasound (LUS) is the latest amongst imaging techniques: it is a radiation-free, inexpensive, point-of-care tool that the clinician can use at the bedside. This review summarises the rapidly growing scientific evidence on LUS in neonatology, dividing it into descriptive and functional applications. We report the description of the main ultrasound features of neonatal respiratory disorders and functional applications of LUS aiming to help a clinical decision (such as surfactant administration, chest drainage etc). Amongst the functional applications, we propose SAFE (Sonographic Algorithm for liFe threatening Emergencies) as a standardised protocol for emergency functional LUS in critical neonates. SAFE has been funded by a specific grant issued by the European Society for Paediatric Research. Future potential development of LUS in neonatology might be linked to its quantitative evaluation: we also discuss available data and research directions using computer-aided diagnostic techniques. Finally, tools and opportunities to teach LUS and expand the research network are briefly presented.

A Multicenter Lung Ultrasound Study on Transient Tachypnea of the Neonate.

BACKGROUND AND AIM: Discordant results that demand clarification have been published on diagnostic lung ultrasound (LUS) signs of transient tachypnea of the neonate (TTN) in previous cross-sectional, single-center studies. This work was conducted to correlate clinical and imaging data in a longitudinal and multicenter fashion. METHODS: Neonates with a gestational age of 34-40 weeks and presenting with TTN underwent a first LUS scan at 60-180 min of life. LUS scans were repeated every 6-12 h if signs of respiratory distress persisted. Images were qualitatively described and a LUS aeration score was calculated. Clinical data were collected during respiratory distress. RESULTS: We enrolled 65 TTN patients. Thirty-one (47.6%) had a sharp echogenicity increase in the lower lung fields (the "double lung point" or DLP sign). On admission, there was no significant difference between patients with and without DLP in Silverman scores (4 ± 1.5 vs. 4 ± 2.1; p = 0.9) or LUS scores (7.6 ± 2.6 vs. 5.6 ± 3.8; p = 0.12); PaO2/FiO2 (249 ± 93 vs. 252 ± 125; p = 0.91). All initial LUS scans (performed at the onset of distress) and 99.5% of all scans showed a regular pleural line with no consolidation, with only 1 neonate showing consolidation in the follow-up scans. The Silverman and LUS scores were significantly correlated (rho = 0.27; p = 0.02). CONCLUSION: A regular pleural line with no consolidation is a consistent finding in TTN. The presence of a DLP is not essential for the LUS diagnosis of TTN. A semi-quantitative LUS score correlates well with the clinical course and could be useful in monitoring changes in lung aeration during TTN.

Visual assessment versus computer-assisted gray scale analysis in the ultrasound evaluation of neonatal respiratory status.

BACKGROUND AND AIM: Lung ultrasound has been used to describe common respiratory diseases both by visual and computer-assisted gray scale analysis. In the present paper, we compare both methods in assessing neonatal respiratory status keeping two oxygenation indexes as standards. PATIENTS AND METHODS: Neonates admitted to the NICU for respiratory distress were enrolled. Two neonatologists not attending the patients performed a lung scan, built a single frame database and rated the images with a standardized score. The same dataset was processed using the gray scale analysis implemented with textural features and machine learning analysis. Both the oxygenation ratio (PaO2/FiO2) and the alveolar arterial oxygen gradient (A-a) were kept as reference standards. RESULTS: Seventy-five neonates with different respiratory status were enrolled in the study and a dataset of 600 ultrasound frames was built. Visual assessment of respiratory status correlated significantly with PaO2/FiO2 (r = -0.55; p<0.0001) and the A-a (r = 0.59; p<0.0001) with a strong interobserver agreement (K = 0.91). A significant correlation was also found between both oxygenation indexes and the gray scale analysis of lung ultrasound scans using regions of interest corresponding to 50K (r = -0.42; p<0.002 for PaO2/FiO2; r = 0.46 p<0.001 for A-a) and 100K (r = -0.35 p<0.01 for PaO2/FiO2; r = 0.58 p<0.0001 for A-a) pixels regions of interest. CONCLUSIONS: A semi quantitative estimate of the degree of neonatal respiratory distress was demonstrated both by a validated scoring system and by computer assisted analysis of the ultrasound scan. This data may help to implement point of care ultrasound diagnostics in the NICU.

Lung Ultrasound Findings in Congenital Pulmonary Airway Malformation.

BACKGROUND AND OBJECTIVE: Congenital pulmonary airway malformation (CPAM) is a group of rare congenital malformations of the lung and airways. Lung ultrasound (LU) is increasingly used to diagnose neonatal respiratory diseases since it is quick, easy to learn, and radiation-free, but no formal data exist for congenital lung malformations. We aimed to describe LU findings in CPAM neonates needing neonatal intensive care unit (NICU) admission and to compare them with a control population. METHODS: A retrospective review of CPAM cases from three tertiary academic NICUs over 3 years (2014-2016) identified five patients with CPAM who had undergone LU examination. LU was compared with chest radiograms and computed tomography (CT) scans that were used as references. RESULTS: CPAM lesions were easily identified and corresponded well with CT scans; they varied from a single large cystic lesion, multiple hypoechoic lesions, and/or consolidation. The first two LU findings have not been described in other respiratory conditions and were not found in controls. CONCLUSION: We provide the first description of LU findings in neonates with CPAM. LU may be used to confirm antenatally diagnosed CPAM and to suspect CPAM in infants with respiratory distress if cystic lung lesions are revealed. Further studies are necessary to define the place of LU in the management of CPAM.

Lung Ultrasound for Diagnosing Pneumothorax in the Critically Ill Neonate.

OBJECTIVES: To evaluate the accuracy of lung ultrasound for the diagnosis of pneumothorax in the sudden decompensating patient. STUDY DESIGN: In an international, prospective study, sudden decompensation was defined as a prolonged significant desaturation (oxygen saturation <65% for more than 40 seconds) and bradycardia or sudden increase of oxygen requirement by at least 50% in less than 10 minutes with a final fraction of inspired oxygen ≥0.7 to keep stable saturations. All eligible patients had an ultrasound scan before undergoing a chest radiograph, which was the reference standard. RESULTS: Forty-two infants (birth weight = 1531 ± 812 g; gestational age = 31 ± 3.5 weeks) were enrolled in 6 centers; pneumothorax was detected in 26 (62%). Lung ultrasound accuracy in diagnosing pneumothorax was as follows: sensitivity 100%, specificity 100%, positive predictive value 100%, and negative predictive value 100%. Clinical evaluation of pneumothorax showed sensitivity 84%, specificity 56%, positive predictive value 76%, and negative predictive value 69%. After sudden decompensation, a lung ultrasound scan was performed in an average time of 5.3 ± 5.6 minutes vs 19 ± 11.7 minutes required for a chest radiography. Emergency drainage was performed after an ultrasound scan but before radiography in 9 cases. CONCLUSIONS: Lung ultrasound shows high accuracy in detecting pneumothorax in the critical infant, outperforming clinical evaluation and reducing time to imaging diagnosis and drainage.

Nitric oxide-sensitive pulmonary hypertension in congenital rubella syndrome.

Persistent pulmonary hypertension is a very rare presentation of congenital virus infection. We discuss the case of complete congenital rubella syndrome presenting at echocardiography with pulmonary hypertension that worsened after ductus ligation. Cardiac catheterization showed a normal pulmonary valve and vascular tree but a PAP = 40 mmHg. The infant promptly responded to inhaled nitric oxide while on mechanical ventilation and was later shifted to oral sildenafil. It is not clear whether our observation may be due to direct viral damage to the endothelium or to the rubella virus increasing the vascular tone via a metabolic derangement.

Lung ultrasound-guided emergency pneumothorax needle aspiration in a very preterm infant.

Pneumothorax is a frequent critical situation in the neonatal intensive care unit. Diagnosis relies on clinical judgement, transillumination and chest radiogram. We report the case of a very preterm infant suddenly developing significant and persistent desaturation and bradycardia. Re-intubation and cardiopulmonary resuscitation were performed. Clinical and cold light examination were not suggestive of pneumothorax according to two experienced neonatologists. A lung ultrasound scan showed evidence of right pneumothorax that was promptly aspirated. Approximately 20 min later, a chest radiogram confirmed the ultrasound diagnosis. Point-of-care lung ultrasound is a useful tool for detecting symptomatic pneumothorax and accelerating its treatment.

Use of neonatal chest ultrasound to predict noninvasive ventilation failure.

BACKGROUND: Noninvasive ventilation is the treatment of choice for neonatal moderate respiratory distress (RD). Predictors of nasal ventilation failure are helpful in preventing clinical deterioration. Work on neonatal lung ultrasound has shown that the persistence of a hyperechogenic, "white lung" image correlates with severe distress in the preterm infant. We investigate the persistent white lung ultrasound image as a marker of noninvasive ventilation failure. METHODS: Newborns admitted to the NICU with moderate RD and stabilized on nasal continuous positive airway pressure for 120 minutes were enrolled. Lung ultrasound was performed and blindly classified as type 1 (white lung), type 2 (prevalence of B-lines), or type 3 (prevalence of A-lines). Chest radiograph also was examined and graded by an experienced radiologist blind to the infant's clinical condition. Outcome of the study was the accuracy of bilateral type 1 to predict intubation within 24 hours from scanning. Secondary outcome was the performance of the highest radiographic grade within the same time interval. RESULTS: We enrolled 54 infants (gestational age 32.5 ± 2.6 weeks; birth weight 1703 ± 583 g). Type 1 lung profile showed sensitivity 88.9%, specificity 100%, positive predictive value 100%, and negative predictive value 94.7%. Chest radiograph had sensitivity 38.9%, specificity 77.8%, positive predictive value 46.7%, and negative predictive value 71.8%. CONCLUSIONS: After a 2-hour nasal ventilation trial, neonatal lung ultrasound is a useful predictor of the need for intubation, largely outperforming conventional radiology. Future studies should address whether including ultrasonography in the management of neonatal moderate RD confers clinical advantages.

Giant congenital melanocytic naevus with proliferative nodules mimicking congenital malignant melanoma: a case report and review of the literature of congenital melanoma.

Congenital malignant melanoma (CMM) is a rare condition that is defined as malignant melanoma recognized at birth. CMM may develop in utero in one of three ways: (1) transmission by metastasis through the placenta from a mother with melanoma; (2) primary melanoma arising within a giant congenital melanocytic naevus (GCMN); (3) primary de novo cutaneous CMM arising in utero. CMM can be confused clinically and histologically with benign proliferative melanocytic lesions such as giant congenital nevi. We describe the case of a patient presenting a GCMN with proliferative nodules, clinically and dermoscopically resembling a CMM, demonstrating the importance of caution in making a diagnosis of MM and highlighting the possibility that benign lesions as GCMN can mimic a malignant melanoma in this age group.