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.

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.

The Predictive Value of Lung Ultrasound Scores in Developing Bronchopulmonary Dysplasia: A Prospective Multicenter Diagnostic Accuracy Study.

BACKGROUND: Different lung ultrasound (LUS) scanning protocols have been used, and the results in terms of diagnostic accuracy are heterogeneous. RESEARCH QUESTIONS: What is the diagnostic accuracy of the LUS score to predict moderate to severe bronchopulmonary dysplasia (msBPD)? Does scanning of posterior lung fields improve the diagnostic accuracy? STUDY DESIGN AND METHODS: This was a multicenter prospective, observational study in six centers. Two LUS aeration scores, one involving only anterolateral lung fields and the other adding the posterior fields were obtained at birth, on the third day of life (DOL), on the seventh DOL, on the 14th DOL, and on the 21st DOL. The diagnostic accuracy of both scores to predict msBPD was assessed at each time point. RESULTS: Eight hundred thirty-two LUS examinations in 298 infants were included. Both LUS score using anterolateral and posterior fields and LUS score using only anterolateral fields showed a similar moderate diagnostic accuracy to predict msBPD on the third DOL (area under the receiver operating characteristic curve [AUC] 95% CI, 0.68-0.85 vs 0.68-0.85; P = .97), seventh DOL (AUC 95% CI, 0.74-0.85 vs 0.74-0.84; P = .26), and 21st DOL (AUC 95% CI, 0.72-0.86 vs 0.74-0.88; P = .17). The LUS score using anterolateral and posterior fields was slightly more accurate at 14th DOL (AUC 95% CI, 0.69-0.83 vs 0.66-0.80; P = .01). A cutoff of 8 points in the LUS score using only anterolateral fields on the seventh DOL provided a sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of 70%, 79%, 3.3, and 0.38, respectively, to predict msBPD. Adding gestational age (GA) and sex improved the discriminative value without significant differences compared with a predictive model based on multiple clinical variables: AUC 95% CI, 0.77-0.88 vs 0.80-0.91 (P = .52). INTERPRETATION: The LUS score is able to predict msBPD from the third DOL with a moderate diagnostic accuracy. Scanning posterior lung fields slightly improved diagnostic accuracy only at the 14th DOL. Adding GA and sex improves the diagnostic accuracy of the LUS scores. The LUS score is useful to stratify BPD risk early after birth.

Lung ultrasound score and diuretics in preterm infants born before 32 weeks: A pilot study.

OBJECTIVE: To describe if weekly determined lung ultrasound (LU) scores in preterm infants born before 32 weeks (PTB32W) change with diuretic therapy. DESIGN: We included infants who received diuretics and compared LU scores according to their evolution on respiratory support (RS) before and after diuretics. RESULTS: We included 18 PTB32W divided into two groups. Both groups were similar in terms of median gestational age: 26 weeks (interquartile range [IQR]: 25-28) in the responders' group and 27 weeks (IQR: 24-28) in the other. They differed, however, in the median number of days on invasive mechanical ventilation: 27 (IQR: 11-43) versus 76 (IQR: 35-117), p = .03; in addition to the number of infants with moderate-severe bronchopulmonary dysplasia: 3 (33%) versus 8 (89%), p = .025. The responders' group showed lower LU scores 2 days after diuretics, with a median LU score of 6 (IQR: 3-12) versus 14 (IQR: 12-17) in the nonresponders group, p = .03; 1 week after (3 [IQR: 0-10] versus 12 [12-12], p = .04); and 3 weeks after (5 [IQR: 3-6] versus 12 [10-15], p = .01). RS also decreased at the same time: 7 out of 9 (78%) were extubated in the responders' group, and 1 out of 9 (11%) in the nonresponders group, p = .02, and these differences remained throughout the entire follow-up. CONCLUSIONS: There is a group of PTB32W patients whose LU score improves after diuretics. This change appears only in those patients that can be weaned off from RS, and at the same period of time as the administration of diuretics.

Lung ultrasound score as early predictor of bronchopulmonary dysplasia in very low birth weight infants.

BACKGROUND: Lung ultrasound (LU) has been widely used to diagnose and monitor acute lung diseases in neonates, but its role in chronic diseases has not been elucidated. OBJECTIVE: We aim to describe the evolution of a lung ultrasound score (LU score) in very low birth weight infants (VLBWI) with and without bronchopulmonary dysplasia (BPD). METHODS: We prospectively included 59 VLBWI and performed LU in the first 24 and 72 hours of life, and then weekly until 36 weeks´ postmenstrual age (PMA). We calculated the LU score as a semiquantitative score representing the aeration (0-3) in three different areas of each lung. RESULTS: The non-BPD group (n = 38) had lower LU score at 1, 2, 3, 4, and 36 weeks' PMA than the BPD group: median score of 1 (0-4) vs 7 (3-10), P < .001; 0 (0-1) vs 7 (4-9), P < .001; 0 (0-1) vs 8 (7-11), P < .001; 0 (0-2) vs 9 (4-12), P < .001; 0 (0-0) vs 3 (0-6), P < .001. A LU score of 5 or above at 1 week of life predicted BPD with a sensitivity (Se) of 71%, specificity (Sp) 80%, area under the ROC curve (AUC) 0.8, and at 2 weeks of life with Se 74%, Sp 100%, and AUC 0.93. An LU score of 4 or above at 4 weeks predicted moderate-severe BPD (Se 100%, Sp 80%, and AUC 0.89). CONCLUSION: In VLBWI without BPD, LU score increases during the first week of life and decreases thereafter, whereas among subjects with BPD, the LU score remains high until 36 weeks´ PMA. LU score can predict the diagnosis of BPD at 1 week and 2 weeks of life, and may predict moderate-severe BPD at 4 weeks of life.

Broad spectrum antibiotics in newborns increase multi-drug resistant infections.

Our objective was to determine if broad spectrum antibiotics (BSA) are associated with multi-resistant bacterial (MRB) infections in neonatal patients. We conducted a case-control study with two groups of patients: those with and without a MRB infection. We included 43 cases and 43 controls. MRB strains were: 21 S. maltophila (49%), 11 ESBL-producing Enterobacteriae (25%), 8 P. aeruginosa (19%) and 3 MRSA (7%). Odds ratio (OR) for MRB after seven days of carbapenems was 4.25 (95% confidence interval (CI) 1.4-17.4) and OR for MRB after seven days of third generation cephalosporin was 8 (95% CI 1.1-34.9). BSA longer than seven days, increases MRB infections 22.5 times in patients with bronchopulmonary dysplasia (BPD). Our data show a clear association between the use of BSA and the development of MRB infections, especially in BPD. Although we cannot state this is a causal relationship, we can recommend avoiding prolonged treatment with these antibiotics in preterm babies at risk of BPD.

Hemoglobin M Disease as a Cause of Cyanosis in a Newborn.

Methemoglobinemia, including the inherited or congenital form, is a known but infrequent cause of neonatal cyanosis. We present the case of a newborn patient with neonatal cyanosis, who was diagnosed with F-M-Osaka methemoglobinemia, and an up-to-date literature review of the disease.

Pantoea agglomerans: ¿un nuevo patógeno en la unidad de cuidados intensivos neonatales?: a new pathogen at the neonatal intensive care unit? / Pantoea agglomerans

La sepsis tardía es especialmente frecuente en los recién nacidos pretérmino, y los bacilos gramnegativos son responsables de los casos más graves con una elevada mortalidad asociada. Pantoea agglomerans es un bacilo gramnegativo que pocas veces se ha descrito como patógeno en el ser humano, menos aún en el recién nacido. Se presenta el caso clínico de un recién nacido pretérmino que sufrió una sepsis fulminante por Pantoea agglomerans en una unidad de cuidados intensivos neonatales. Hasta la fecha no se ha descrito ningún caso de sepsis por P. agglomerans en esta población en España.

Late-onset sepsis is very frequent among preterm infants and cases due to Gram negative pathogens have elevated morbidity and mortality. Pantoea agglomerans is a Gram negative organism which has been rarely reported causing disease in humans. We present a case of P. agglomerans late-onset fulminant sepsis in a preterm newborn at a neonatal intensive care unit. Up to date none P. agglomerans sepsis has been reported among this population in our country.