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Bronchopulmonary dysplasia (BPD) is one of the most common and severe complications of extreme prematurity, affecting approximately 40% of infants born before 28 weeks of gestation. Despite advances in neonatal care and improved survival rates for extremely preterm infants, the incidence of BPD remains high. BPD is associated with significant short- and long-term morbidity, including chronic respiratory impairment, pulmonary hypertension, recurrent respiratory infections, and neurodevelopmental sequelae. Current diagnosis of BPD is based on the need for respiratory support at 36 weeks postmenstrual age, limiting opportunities for early therapeutic intervention. Since structural lung injury may become irreversible within the first weeks of life, the identification of reliable early predictors of BPD is a major clinical priority. Lung ultrasound (LUS) is a non-invasive, radiation-free, bedside imaging technique increasingly used in neonatal intensive care units. The Lung Ultrasound Score (LUS) provides a quantitative assessment of lung aeration and has demonstrated utility in predicting several neonatal respiratory outcomes. Recent studies suggest that both LUS and pleural line abnormalities detected during the first weeks of life may be associated with the subsequent development of BPD, although evidence remains heterogeneous and no universally validated predictive method is currently available.
Bronchopulmonary dysplasia (BPD) is one of the most frequent and severe complications of extreme prematurity and remains a major cause of neonatal morbidity despite significant advances in perinatal and neonatal care. BPD is associated with long-term respiratory, cardiovascular, and neurodevelopmental complications and continues to affect a substantial proportion of infants born at very low gestational ages. Current diagnostic definitions of BPD rely on the need for respiratory support at 36 weeks postmenstrual age. Consequently, diagnosis is established after the period during which preventive and disease-modifying interventions are likely to be most effective. Evidence suggests that irreversible structural changes of the developing lung may occur within the first weeks of life, making early identification of infants at high risk of BPD a clinical priority. Lung ultrasound (LUS) has emerged as a safe, non-invasive, bedside imaging modality capable of assessing lung aeration and pulmonary abnormalities in preterm infants. The Lung Ultrasound Score (LUS) provides a quantitative evaluation of lung aeration loss and has shown promising results in predicting respiratory outcomes in neonatal populations. In addition, pleural line abnormalities, including thickening, irregularity, fragmentation, and subpleural consolidations, have been associated with the subsequent development of BPD. Although several studies have suggested that lung ultrasound findings obtained during the first two weeks of life may predict BPD, no standardized and universally accepted method for early risk stratification is currently available. Furthermore, the optimal ultrasound parameters and their predictive performance remain uncertain. The first 15 days of life represent a critical window for assessing the risk of BPD and for identifying infants who may benefit from preventive therapeutic strategies before irreversible lung injury develops. The aim of this study is to evaluate whether lung ultrasound findings obtained during the first two weeks of life, including Lung Ultrasound Score and pleural line characteristics, are associated with the subsequent development of BPD and may therefore serve as early prognostic markers. Because two clinical definitions of BPD are currently widely used in clinical practice and research, and no clear evidence has demonstrated the superiority of one definition over the other for diagnostic or prognostic purposes, both the Jobe and Bancalari definition and the Jensen definition will be applied in this study. The primary objective is to evaluate the diagnostic performance of the Lung Ultrasound Score measured at 7 and 14 days of life for the prediction of BPD and moderate-to-severe BPD in preterm infants.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Preterm infants (<32 weeks' gestational age) | Consecutive preterm infants born at less than 32 weeks' gestational age and admitted to participating NICUs during the study period. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lung ultrasound at 7 (±1) days of life | Diagnostic Test | Lung ultrasound will be performed at 7 (±1) days days of life by physicians experienced in lung ultrasound, defined as any physician who has previously completed a theoretical and practical training course in lung ultrasound and has independently performed at least 20 lung ultrasound examinations. Six thoracic regions will be examined in order to determine the Lung Ultrasound Score (LUS) and to assess pleural line characteristics: right and left anterior superior, right and left anterior inferior, and right and left lateral regions. |
| Measure | Description | Time Frame |
|---|---|---|
| Diagnostic accuracy of Lung Ultrasound for prediction of bronchopulmonary dysplasia | Diagnostic performance of the Lung Ultrasound Score (LUS) for predicting bronchopulmonary dysplasia, defined according to both the Jobe/Bancalari and Jensen classifications. | 7 days, 14 days |
| Diagnostic accuracy of Lung Ultrasound Score for prediction of moderate-to-severe bronchopulmonary dysplasia | Diagnostic performance of the Lung Ultrasound Score obtained for predicting moderate-to-severe bronchopulmonary dysplasia. | 7 days, 14 days |
| Measure | Description | Time Frame |
|---|---|---|
| Association between pleural line abnormalities and bronchopulmonary dysplasia | Association between the presence of pleural line abnormalities detected by lung ultrasound and subsequent diagnosis of bronchopulmonary dysplasia. | 7 days, 14 days |
| Duration of invasive mechanical ventilation |
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Inclusion Criteria:
Exclusion Criteria:
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Consecutive preterm infants born at less than 32 weeks' gestational age and admitted to participating NICUs during the study period.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Eleonora Balestri, MD | Contact | 0522 296278 | eleonora.baIestri@ausl.re.it | |
| Ilaria Bassoli, MD | Contact | 0522 296278 | ilaria.bassoli@ausl.re.it |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Neonatology and Neonatal Intensive Care Unit AOU Policlinico Modena | Recruiting | Modena | Italy |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38087005 | Background | Zong H, Huang Z, Fu Y, Chen X, Yu Y, Huang Y, Huang Y, Sun H, Yang C. Lung ultrasound score as a tool to predict severity of bronchopulmonary dysplasia in neonates born </=25 weeks of gestational age. J Perinatol. 2024 Feb;44(2):273-279. doi: 10.1038/s41372-023-01811-4. Epub 2023 Dec 12. | |
| 33374021 | Background |
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| ID | Term |
|---|---|
| D001997 | Bronchopulmonary Dysplasia |
| D047928 | Premature Birth |
| ID | Term |
|---|---|
| D055397 | Ventilator-Induced Lung Injury |
| D055370 | Lung Injury |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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|
| Lung ultrasound at 14 (±2) days of life | Diagnostic Test | Lung ultrasound will be performed at 14 (±2) days days of life by physicians experienced in lung ultrasound, defined as any physician who has previously completed a theoretical and practical training course in lung ultrasound and has independently performed at least 20 lung ultrasound examinations. Six thoracic regions will be examined in order to determine the Lung Ultrasound Score (LUS) and to assess pleural line characteristics: right and left anterior superior, right and left anterior inferior, and right and left lateral regions. |
|
Association between Lung Ultrasound Score (LUS) obtained during the first two weeks of life and the total duration of invasive mechanical ventilation in preterm infants |
| 7 days, 14 days |
| Duration of supplemental oxygen therapy | Association between Lung Ultrasound Score (LUS) obtained during the first two weeks of life and the total duration of supplemental oxygen therapy in preterm infants. | 7 days, 14 days |
| Neonatology and Neonatal Intensive Care Unit AOU Padova | Recruiting | Padova | Italy |
|
| Neonatology and Neonatal Intensive Care Unit AUSL - IRCCS of Reggio Emilia | Recruiting | Reggio Emilia | Italy |
|
| Neonatology and Neonatal Intensive Care Unit Policlinico Universitario A. Gemelli IRCCS, Roma. | Recruiting | Roma | Italy |
|
| Hoshino Y, Arai J, Miura R, Takeuchi S, Yukitake Y, Kajikawa D, Kamakura T, Horigome H. Lung Ultrasound for Predicting the Respiratory Outcome in Patients with Bronchopulmonary Dysplasia. Am J Perinatol. 2022 Aug;39(11):1229-1235. doi: 10.1055/s-0040-1721848. Epub 2020 Dec 29. |
| 35305612 | Background | Sun YH, Du Y, Shen JR, Ai DY, Huang XY, Diao SH, Lin SB, Zhang R, Yuan L, Yang YP, He LL, Qin XJ, Zhou JG, Chen C. A modified lung ultrasound score to evaluate short-term clinical outcomes of bronchopulmonary dysplasia. BMC Pulm Med. 2022 Mar 19;22(1):95. doi: 10.1186/s12890-022-01885-4. |
| 34237347 | Background | Mohamed A, Mohsen N, Diambomba Y, Lashin A, Louis D, Elsayed Y, Shah PS. Lung Ultrasound for Prediction of Bronchopulmonary Dysplasia in Extreme Preterm Neonates: A Prospective Diagnostic Cohort Study. J Pediatr. 2021 Nov;238:187-192.e2. doi: 10.1016/j.jpeds.2021.06.079. Epub 2021 Jul 6. |
| 33352083 | Background | Loi B, Vigo G, Baraldi E, Raimondi F, Carnielli VP, Mosca F, De Luca D. Lung Ultrasound to Monitor Extremely Preterm Infants and Predict Bronchopulmonary Dysplasia. A Multicenter Longitudinal Cohort Study. Am J Respir Crit Care Med. 2021 Jun 1;203(11):1398-1409. doi: 10.1164/rccm.202008-3131OC. |
| 33755776 | Background | Liu X, Lv X, Jin D, Li H, Wu H. Lung ultrasound predicts the development of bronchopulmonary dysplasia: a prospective observational diagnostic accuracy study. Eur J Pediatr. 2021 Sep;180(9):2781-2789. doi: 10.1007/s00431-021-04021-2. Epub 2021 Mar 23. |
| 33689782 | Background | Alonso-Ojembarrena A, Serna-Guerediaga I, Aldecoa-Bilbao V, Gregorio-Hernandez R, Alonso-Quintela P, Concheiro-Guisan A, Ramos-Rodriguez A, de Las Heras-Martin M, Rodeno-Fernandez L, Oulego-Erroz I. The Predictive Value of Lung Ultrasound Scores in Developing Bronchopulmonary Dysplasia: A Prospective Multicenter Diagnostic Accuracy Study. Chest. 2021 Sep;160(3):1006-1016. doi: 10.1016/j.chest.2021.02.066. Epub 2021 Mar 6. |
| 32665687 | Background | Oulego-Erroz I, Alonso-Quintela P, Terroba-Seara S, Jimenez-Gonzalez A, Rodriguez-Blanco S. Early assessment of lung aeration using an ultrasound score as a biomarker of developing bronchopulmonary dysplasia: a prospective observational study. J Perinatol. 2021 Jan;41(1):62-68. doi: 10.1038/s41372-020-0724-z. Epub 2020 Jul 14. |
| 30127522 | Background | Raimondi F, Yousef N, Migliaro F, Capasso L, De Luca D. Point-of-care lung ultrasound in neonatology: classification into descriptive and functional applications. Pediatr Res. 2021 Sep;90(3):524-531. doi: 10.1038/s41390-018-0114-9. Epub 2018 Jul 20. |
| 34515177 | Background | Aldecoa-Bilbao V, Velilla M, Teresa-Palacio M, Esponera CB, Barbero AH, Sin-Soler M, Sanz MI, Salvia Roiges MD. Lung Ultrasound in Bronchopulmonary Dysplasia: Patterns and Predictors in Very Preterm Infants. Neonatology. 2021;118(5):537-545. doi: 10.1159/000517585. Epub 2021 Aug 13. |
| D007235 |
| Infant, Premature, Diseases |
| D007232 | Infant, Newborn, Diseases |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D007752 | Obstetric Labor, Premature |
| D007744 | Obstetric Labor Complications |
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |