Association of Lung Ultrasound score with Large Patent Ductus Arteriosus in Preterm Neonates during the transitional period

Association of Lung Ultrasound score with Large Patent Ductus Arteriosus in Preterm Neonates during the transitional period | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Association of Lung Ultrasound score with Large Patent Ductus Arteriosus in Preterm Neonates during the transitional period Adel Mohamed, Nada Mohsen, Jenna Ibrahim, Seungwoo Lee, Ashraf Kharrat, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6258106/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 20 May, 2025 Read the published version in European Journal of Pediatrics → Version 1 posted 9 You are reading this latest preprint version Abstract Background: Recent studies suggested lung ultrasound (LU) as a useful, non-invasive bedside tool for assessing pulmonary edema; however, its utility in identifying preterm neonates with large patent ductus arteriosus (L-PDA) is limited. Objective: To evaluate the association of LU score (LUS) in preterm neonates with L-PDA during the transitional period and explore correlation of LUS with echocardiographic indicators. Methods: Among 152 neonates born < 29 weeks’ gestation and had LU performed at day-of-life (DOL) three for a previous prospective study, 54 neonates had concomitant echocardiography documenting PDA presence, diameter, and variables for shunt volume. We included in the analysis neonates who had LU and Echo on DOL 3. Neonates with L-PDA were compared to those with absent or small PDA. Univariate, multivariate, and Pearson’s correlation coefficients analyses were conducted. Results: Of the 54 infants included in the study, 32 (59%) were diagnosed with L-PDA. There were no significant differences in baseline characteristics between the L-PDA and no-L-PDA group. Univariate analysis showed no association between LUS and L-PDA. Similarly, multivariate analysis found that a one-point increment of LUS was not associated to L-PDA (adjusted OR: 1.19; 95% CI: 0.89–1.59). LUS demonstrated a significant correlation with respiratory severity score and a weak correlation with PDA diameter, but no significant associations with other PDA shunt volume variables. Conclusion: In this cohort, LUS was not associated with L-PDA during the transition period. Larger studies are required to confirm these findings and further explore the clinical utility of LUS in assessing PDA. Neonates Lung ultrasound Echocardiography Patent ductus arteriosus Preterm infant. Figures Figure 1 Introduction In preterm neonates, patent ductus arteriosus (PDA) presents a common and complex clinical challenge, often contributing to increased morbidity and complications[ 1 , 2 ]. Significant left-to-right shunting in PDA leads to pulmonary over-circulation, increased left ventricular output (LVO), and decreased systemic perfusion, with potential impacts on both cardiovascular and respiratory systems[ 1 , 3 , 4 ]. Traditionally, echocardiographic markers such as ductal diameter, left atrium-to-aortic root (LA/Ao) ratio, and pulmonary artery flow pattern have been used to assess PDA severity[ 5 ]. While these indicators guide clinical decisions, they primarily focus on cardiovascular effects and may not fully capture the respiratory consequences of PDA, such as pulmonary congestion that lead to increased work of breathing[ 6 , 7 ]. Lung ultrasound (LU) has emerged as a promising tool in the neonatal intensive care unit (NICU) for the assessment of lung pathology, offering a non-invasive, radiation-free, bedside option that can be repeated as needed[ 8 ]. It has shown utility in conditions like respiratory distress syndrome (RDS), transient tachypnea of the newborn (TTN), and bronchopulmonary dysplasia (BPD) [ 9 , 10 ]. The lung ultrasound score (LUS), which quantifies the severity of B-lines and consolidations, provides a semiquantitative assessment of lung aeration and pulmonary congestion[ 11 ]. This capability makes LUS particularly relevant in assessing the pulmonary effects of large PDA, (L-PDA) which often causes increased respiratory effort and oxygen requirements due to pulmonary over-circulation[ 12 ]. Given its ability to assess lung parenchymal involvement, LUS may complement echocardiography by providing direct, real-time insights into PDA-related pulmonary effects[ 13 , 14 ]. Additionally, LUS could potentially be used to monitor changes in pulmonary status following treatment, enhancing individualized care and improving respiratory outcomes[ 15 ]. Nevertheless, data on the correlation between LUS and echocardiographic markers in preterm neonates with L-PDA is limited. This study aims to evaluate the association of LUS in preterm neonates with L-PDA during immediate postnatal transition and explore its correlation with echocardiographic indicators. Materials and Methods Study design, setting, and population Previously at our center 152 neonates born at less than 29 weeks’ gestational age (GA) had LU documented for a prospective study[ 16 ], and were considered eligible for inclusion. Among these neonates, 54 neonates who had a clinical targeted neonatal echocardiography (TNE) within 24 hours of LU with documentation of PDA characteristics were included in the study. This study was approved by the Research Ethics Board of Mount Sinai Hospital. Lung Ultrasound Procedure Lung ultrasounds were conducted on postnatal day three using a portable ultrasound machine (Z. One PRO, Mindray North America) equipped with a high-resolution linear probe (L20-5). Infants were scanned in the supine position after remaining in this position for at least 1 hour to minimize overestimation of lung ultrasound scores (LUS) due to dependent lung areas[ 17 ]. Each lung was scanned in three zones (upper anterior, lower anterior, and lateral) by personnel trained in neonatal lung ultrasound. Images were securely transferred to a password-protected external hard drive. Two expert investigators, who were blinded to clinical condition of study population, had independently calculated the LUS (total score ranging from 0–18)[ 11 ] after the study's completion. Targeted Neonatal Echocardiography: Our unit has a mature, well-established TNE-based hemodynamic consultation program. Under this program, TNEs are performed either by an experienced TNE staff physician or trained sonographer or fellow under direct supervision. During the study period, all TNEs were performed with the GE E95 ultrasound machine and 12 MHz phase array probe, using our unit’s published standardized TNE imaging protocol[ 18 ]. All TNEs are reported on the same day by one of the four TNE staff physicians. As a standard practice in our program, all TNE reports includes recording PDA presence and key related hemodynamic parameters indicative of shunt volume. For this study, the following parameters were recorded for all included patients from the TNE reports: PDA presence and diameter in mm, left ventricular output and the ratio of left atrial and aortic root diameter, measured using standard methodology[ 19 ]. Study Cohort Categorization The definition of hemodynamically significant PDA (Hs-PDA) remains debated, with little consensus, especially during immediate postnatal period[ 20 , 21 ]. While Hs-PDA scoring systems exist, they lack validation in large trials.[ 22 , 23 ]. For this study, we used the pragmatic definition to divide study cohort into those with large PDA (L-PDA, defined as PDA with diameter ≥ 1.5 mm and predominantly left-to-right shunt) and those with absent or small PDA (diameter < 1.5 mm). Data collection Study data were sourced from the original study database and supplemented with information from patients' electronic medical records. The dataset included demographic and clinical details such as gestational age, sex, birth weight, mode of delivery, Apgar score at 5 minutes, antenatal steroid administration, Score for Neonatal Acute Physiology with Perinatal Extension-II (SNAPPE-II) score, surfactant use, mechanical ventilation, early-onset sepsis diagnosis, lung ultrasound scores, ventilation mode, average mean airway pressure (MAP), fraction of inspired oxygen (FiO2), and respiratory severity score [RSS = FiO2 x MAP] at the time of the scan, and TNE data related to PDA (PDA diameter, LA: Ao, and LVO). Outcomes The primary aim of this study was to evaluate the association of LUS in detecting the presence of a L-PDA as identified by TNE. The secondary aim was to assess the correlation between LUS findings and echocardiographic indices, including PDA diameter, LA:Ao ratio, and LVO. Statistical analysis Baseline demographic and outcome variables were compared between the two groups (L-PDA and No/Small PDA). Categorical variables were analyzed using the Chi-square or Fisher’s exact test, while continuous variables were evaluated with the Student’s t-test or Wilcoxon Rank-Sum test, as appropriate. Logistic regression was employed to assess the association between change in LUS and L-PDA, adjusting for GA, antenatal steroid administration, invasive mechanical ventilation (IMV), and respiratory severity score (RSS = fraction of inspired oxygen × mean airway pressure) at the time of LU. For the logistic model, both unadjusted and adjusted odds ratios were calculated with L-PDA as the dependent variable and change in LUS as independent variable. The odds ratios for both change in LUS and change in RSS were calculated based on a one-point increase in the score. Pearson’s correlation coefficients were calculated to explore linear relationships between LUS, RSS, PDA diameter, LVO, and LA:Ao. All analyses were conducted using SAS software (version 9.4, SAS Institute Inc., Cary, NC), with statistical significance set at p < 0.05. Results Among the 54 preterm neonates included in the study, 32 (59%) were identified as having L-PDA. Baseline characteristics were comparable between the L-PDA and No/Small PDA groups, with no significant differences observed in GA at birth, age at assessment, respiratory support, and RSS at the time of LU scan (Table 1 ). Univariate analysis revealed no statistically significant differences in LUS between the groups (Table 2 and e-Figure 1). For TNE variables, while LVO was higher in the L-PDA group, LA:Ao was similar (Table 2 ). Table 1 Demographic Characteristics of Study Participants L-PDA (n = 32) No/small PDA (n = 22) P value GA at birth (wk), median (IQR) 25.00 (24.4, 26.3) 25.45 (24.6, 27) 0.35 Birth weight (g), median (IQR) 693 (610, 885) 775 (620, 880) 0.28 Male, n (%) 16 (50) 11 (50) 1.00 SGA, n (%) 4 (13) 0 (0) 0.14* Antenatal steroids, n (%) 24 (75) 13 (59) 0.22 SNAPPE-II, median (IQR) 14 (9, 23.5) 14 (5, 14) 0.18 Caesarean delivery, n (%) 17 (53) 11 (50 (11) 0.82 Surfactant administration, n (%) 28 (88) 22 (100) 0.14* Age at assessment (week), median (IQR) 25.4 (24.7, 26.6) 25.9 (25.0, 27.3) 0.53 BPD (moderate, severe), n % 31 (97) 16 (73) 0.01* Mortality prior to discharge, n % 3 (9) 2 (9) 1.00* Respiratory Support at the Time of Assessment IMV at the scan, n % 16 (50) 8 (36) 0.32 NIV at the scan, n % 16 (50) 14 (64) 0.32 MAP at the scan mean (SD) 10.06 (2.18) 9.73 (2.39) 0.60 FiO2 at the scan, median (IQR) 0.26 (0.21, 0.34) 0.23 (0.21, 0.29) 0.28 RSS at scan, mean (SD) 2.87 (1.22) 2.55 (1.15) 0.34 L-PDA: Large- patent ductus arteriosus; GA: gestational age; IQR: interquartile range; SGA: small for GA; SNAPPE-II: Score for Neonatal Acute Physiology with Perinatal Extension-II; BPD: bronchopulmonary dysplasia; IMV: Invasive Mechanical Ventilation; NIV: Non-invasive ventilation; MAP: Main Airway Pressure; FiO2: fraction of inspired oxygen: RSS: Respiratory severity score (= FiO2 x MAP); SD: standard deviation. Notes: the reported p-values were based on the comparison between two groups using Chi-square test or Fisher’s exact test* for categorical variables and Student t test or Wilcoxon-Rank-Sum test as appropriate for continuous variables. Table 2 Comparison of LUS and Echocardiographic Indices between Groups. L-PDA (n = 32) No/small PDA (n = 22) P value LUS, median (IQR) 15 (14, 16) 14.5 (11, 16) 0.31 PDA diameter (mm), mean (SD) 2.29 (0.48) 1.25 (0.16) < 0.0001 La:Ao, mean (SD) 1.66 (0.26) 1.57 (0.26) 0.25 LVO (ml/kg/min), mean (SD) 287.09 (82.72) 226.61 (69.72) 0.008 LUS: Lung ultrasound score; PDA: Patent Ductus Arteriosus; La:Ao: left atrial-to-aortic root ratio; LVO: left ventricular output. The reported p-values were based on the comparison between two groups Wilcoxon-Rank-Sum test. A multiple logistic regression model found no significant association between change in LUS (a one-point increment of LUS) and the presence of L-PDA (adjusted OR: 1.19; 95% CI: 0.89–1.59) (Table 3 ). However, LUS showed a statistically significant positive correlation with RSS (r = 0.34, p = 0.01) (Fig. 1 ) but not with TNE indices of LVO or LA:Ao. Additionally, PDA diameter demonstrated a weak positive correlation with RSS, that did not reach statistical significance (r = 0.28, p = 0.07) (e-Figure 2). Table 3 Multivariate Logistic Regression Analyses Odds Ratios (95% CI) L-PDA vs no-PDA/small PDA Unadjusted (95% CI) Adjusted (95% CI) LUS (one unit increase in score) 1.20 (0.95, 1.51) 1.19 (0.89, 1.59) RSS (one unit increase in score) 1.27 (0.78, 2.09) 1.23 (0.64, 2.35) CI: Confidence Interval Adjusted OR was based on the multiple logistic regression model adjusted for LUS, GA, IMV, RSS, and antenatal steroid. Discussion In this study, early LUS within the first three postnatal days was not associated with L-PDA in either univariate or multivariate analyses. Two factors may explain this finding. First, our cohort primarily consisted of extremely preterm infants (mean GA 25 weeks) with RDS, whose sonographic features (e.g., echogenic "white lung," pleural line abnormalities) overlap with those of pulmonary congestion from L-PDA, potentially masking PDA-related changes.[ 24 ] Second, during the immediate postnatal transition, L-PDA may not cause significant pulmonary changes due to limited duration of exposure and low shunt volume. Thus, combining LUS with echocardiography may provide a more comprehensive evaluation of neonatal cardiorespiratory status, facilitating accurate diagnosis and management. On the other hand, our study revealed a significant positive correlation between LUS and the RSS, indicating that LUS effectively reflects respiratory disease severity. This finding underscores its potential utility in assessing pulmonary status in preterm infants, independent of PDA presence.[ 25 , 26 ] Several studies have explored the relationship between LUS and the presence of significant PDA with left-to-right shunting[ 12 , 15 , 27 – 30 ]. Yu et al[ 12 ] reported significantly higher LUS in the persistent PDA group compared to the no-PDA group (P < 0.05). However, direct comparison with our findings is challenging due to uncertainties regarding whether "persistent PDA" specifically referred to L-PDA, the inclusion of more mature neonates (GA < 37 weeks), and the absence of data on respiratory status at the time of assessment. These factors make it difficult to attribute their findings solely to PDA. In a case series, Savoia et al.[ 15 ] studied five infants (birth weight: 787 ± 88 grams; GA: 25.6 ± 0.7 weeks) who underwent PDA ligation on postnatal day 41. They reported significant reductions in LUS and LVO post-ligation. However, the small sample size limits the generalizability of their findings. Additionally, the study’s timing differs markedly from ours, as we conducted LU during the transitional period (postnatal day 3) when RDS is the predominant lung pathology, leading to similar LU patterns as seen in infants with significant PDA. Martini et al.[ 27 ] conducted daily LUS and echocardiography in 46 infants born at a median GA of 29 weeks (IQR: 27–31) and found higher LUS in those with HsPDA compared to those with a restrictive or closed ductus. However, their findings did not align with ours, likely due to their inclusion of neonates with higher GA. This is a crucial distinction, as LUS is inversely related to GA, infants born before 28 weeks typically have higher LUS, primarily due to RDS, whose patterns can resemble those seen in HsPDA [ 31 ]. Similarly, Ozdemir et al.[ 28 ] performed LUS and echocardiography on days 1, 3, and 7 after birth in 107 infants born at GA < 34 weeks and found higher LUS in HsPDA cases. As with Martini et al., their inclusion of more mature neonates (< 34 weeks) may explain the differences in findings. In contrast, Zong et al.[ 29 ] prospectively studied 81 infants (median GA: 25 weeks, IQR: 24.4–25.4), performing echocardiography followed by LUS on day 14. Using a 12-area scoring system (0–48), they identified an LUS cutoff of 36 that predicted PDA ligation with 96% sensitivity, 86% specificity, and predictive values of 82% (positive) and 98% (negative). However, differences in scoring methods and scan timing (day 14 vs. day 3 in our study) limit direct comparison. Both our findings and those of Zong et al. align with Alonso-Ojembarrena et al.[ 31 ], who reported that LUS progression varies with postnatal age. This highlights the dynamic nature of lung ultrasound findings over time and underscores the importance of considering postnatal age when interpreting LUS in preterm infants. Alonso-Ojembarrena et al.[ 30 ] found that LUS correlated with PDA size and left ventricular function in infants born after 28 weeks but not in those born before 28 weeks. This aligns with our findings, reinforcing that in extremely preterm neonates, early LUS primarily reflects prematurity and RDS severity rather than PDA status. In our study, both groups exhibited relatively high LUS, regardless of PDA presence, highlighting the predominant lung pathology of RDS in extremely preterm infants. This suggests that while LUS effectively detects generalized lung disease, its ability to distinguish pulmonary congestion due to L-PDA from RDS in the early transitional period is limited. Therefore, echocardiography remains essential for identifying cardiac causes of pulmonary congestion. Integrating LUS with echocardiography provides a more comprehensive assessment of neonatal cardiorespiratory status, enhancing diagnostic accuracy and guiding clinical management. This study had several limitations. First, not all data were collected prospectively, and reliance on medical records may have introduced selection and information bias. Second, the small sample size may have reduced statistical power to detect subtle associations. Third, variations in clinical management, including respiratory support and PDA treatment, could have influenced the outcomes. In conclusion, there was no association between LUS and L-PDA during the first three postnatal days in this cohort. This finding may reflect the limitations of LUS in detecting pulmonary overcirculation in the setting of RDS or the minimal impact of L-PDA (low shunt volume, short duration) on pulmonary pathology during early transition period. Future studies with larger cohorts are required to confirm these findings and further explore the clinical utility of LUS in assessing PDA. Abbreviations LU - Lung Ultrasound LUS -Lung Ultrasound Score PDA - patent ductus arteriosus LA: Ao - left atrium: Aortic root ratio LPDA- Large patent ductus arteriosus LVO - left ventricular output RDS- respiratory distress syndrome RSS - respiratory severity score TNE- Targeted neonatal echocardiography HsPDA-Hemodynamic significant patent ductus arteriosus SNAPPE-II – Score for Neonatal Acute Physiology with Perinatal Extension-II Declarations Acknowledgements: We would also like to thank the families and nurses in Mount Sinai Hospital who support our research program. Guarantor: AM, who takes responsibility for the content of the manuscript, including the data and analysis (OriginalResearch) Author contributions: AM conceive the research idea, design the study, and manuscript writing . AM had full access to all of the data and takes responsibility for the content of this manuscript, including study design, data and data analysis. The study design was conducted by AM and AJ; data collection was performed by JI. Data analysis was performed by SL and AM. The manuscript was prepared by AM then edited by PS, AK, NM, and AJ. All authors of this study approved the final draft of the manuscript Ethics approval: Local research ethics approval was obtained (Mount Sinai Hospital REB (22-0233-C), Toronto, On, Canada. Authors certify that the study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Consent to participate: Not applicable given the retrospective nature of the study Consent for publication: All the authors have seen the final version of the manuscript and gave their full consent for the publication. Conflicts of interest: The authors have no financial or completing conflicts of interest to declare. Funding: This study was not supported by any funding sources. Abstract publication/presentation: Portions of this paper were presented at the 2024 Pediatric Academic Society (PAS) meeting in Toronto, Canada, as a poster presentation. References Hamrick SEG et al (2020) Patent Ductus Arteriosus Preterm Infant Pediatr, 146(5) Sung SI et al (2019) Natural evolution of ductus arteriosus with noninterventional conservative management in extremely preterm infants born at 23–28 weeks of gestation. PLoS ONE 14(2):e0212256 Clyman RI (2018) Patent ductus arteriosus, its treatments, and the risks of pulmonary morbidity. Semin Perinatol 42(4):235–242 Fowlie PW, Davis PG, McGuire W (2010) Prophylactic intravenous indomethacin for preventing mortality and morbidity in preterm infants. 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Clin Perinatol 47(3):617–639 Mitra S et al (2018) Association of Placebo, Indomethacin, Ibuprofen, and Acetaminophen With Closure of Hemodynamically Significant Patent Ductus Arteriosus in Preterm Infants: A Systematic Review and Meta-analysis. JAMA 319(12):1221–1238 McNamara PJ, Sehgal A (2007) Towards rational management of the patent ductus arteriosus: the need for disease staging. Arch Dis Child Fetal Neonatal Ed 92(6):F424–F427 El-Khuffash A et al (2015) A Patent Ductus Arteriosus Severity Score Predicts Chronic Lung Disease or Death before Discharge. J Pediatr 167(6):1354–1361e2 Copetti R et al (2008) Lung ultrasound in respiratory distress syndrome: a useful tool for early diagnosis. Neonatology 94(1):52–59 Sabour S (2019) Lung ultrasound in evaluating the severity of neonatal respiratory distress syndrome: Methodological issues on diagnostic value and prediction to avoid misinterpretation. Eur J Radiol 120:108663 Pang H et al (2019) Diagnostic value of lung ultrasound in evaluating the severity of neonatal respiratory distress syndrome. Eur J Radiol 116:186–191 Martini S et al (2023) Impact of patent ductus arteriosus on non-invasive assessments of lung fluids in very preterm infants during the transitional period. Eur J Pediatr 182(9):4247–4251 Ozdemir M et al (2024) Lung ultrasound score in the decision of patent ductus arteriosus closure in neonates. J Clin Ultrasound 52(4):415–425 Zong H et al (2023) Lung ultrasound score predicts patent ductus arteriosus ligation among neonates =25 weeks</at. Pediatr Pulmonol 58(9):2487–2494 Alonso-Ojembarrena A (2023) P.d.M.U.H., San Fernando, Andalucia, Spain; Pamela Zafra-Rodriguez, Relationship between lung ultrasound scores and echocardiographic measurements in very low birth weight infants. PAS 2023. 126 Alonso-Ojembarrena A et al (2022) Lung Ultrasound Scores Progress Differently in Extreme and Very Preterm Infants after Birth: A Multicentre Prospective Study. Neonatology 119(5):558–566 Additional Declarations No competing interests reported. Supplementary Files eFigure1.jpg eFigure2.jpg Cite Share Download PDF Status: Published Journal Publication published 20 May, 2025 Read the published version in European Journal of Pediatrics → Version 1 posted Editorial decision: Revision requested 16 Apr, 2025 Reviews received at journal 14 Apr, 2025 Reviews received at journal 08 Apr, 2025 Reviewers agreed at journal 29 Mar, 2025 Reviewers agreed at journal 29 Mar, 2025 Reviewers invited by journal 29 Mar, 2025 Editor assigned by journal 24 Mar, 2025 Submission checks completed at journal 24 Mar, 2025 First submitted to journal 19 Mar, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6258106","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":443833841,"identity":"36851c23-b2c7-4936-9573-82ee19c4b062","order_by":0,"name":"Adel 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05:38:06","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6258106/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6258106/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00431-025-06186-6","type":"published","date":"2025-05-20T15:57:27+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":81172073,"identity":"f6969d5c-6cba-47b8-b3af-d132ff2ee711","added_by":"auto","created_at":"2025-04-23 05:33:22","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":38519,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelation between RSS and LUS for the study cohort\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6258106/v1/4868ce37c938a306bfee89fa.jpg"},{"id":83460006,"identity":"7bd05ab9-b978-4074-8ede-d1d67e85f9ad","added_by":"auto","created_at":"2025-05-26 16:08:49","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":700347,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6258106/v1/3103584a-7c08-4ff5-a15b-d081175f0a25.pdf"},{"id":81172076,"identity":"d8752515-d224-4c9c-9c4c-cb752bcc360a","added_by":"auto","created_at":"2025-04-23 05:33:22","extension":"jpg","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":134641,"visible":true,"origin":"","legend":"","description":"","filename":"eFigure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6258106/v1/dd74a88b69af2fca02d020e7.jpg"},{"id":81172080,"identity":"9294b425-a364-461e-abcd-338f9fd32a5a","added_by":"auto","created_at":"2025-04-23 05:33:23","extension":"jpg","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":215949,"visible":true,"origin":"","legend":"","description":"","filename":"eFigure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6258106/v1/3062463f982f360f8e3428f6.jpg"}],"financialInterests":"No competing interests reported.","formattedTitle":"Association of Lung Ultrasound score with Large Patent Ductus Arteriosus in Preterm Neonates during the transitional period","fulltext":[{"header":"Introduction","content":"\u003cp\u003eIn preterm neonates, patent ductus arteriosus (PDA) presents a common and complex clinical challenge, often contributing to increased morbidity and complications[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Significant left-to-right shunting in PDA leads to pulmonary over-circulation, increased left ventricular output (LVO), and decreased systemic perfusion, with potential impacts on both cardiovascular and respiratory systems[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Traditionally, echocardiographic markers such as ductal diameter, left atrium-to-aortic root (LA/Ao) ratio, and pulmonary artery flow pattern have been used to assess PDA severity[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. While these indicators guide clinical decisions, they primarily focus on cardiovascular effects and may not fully capture the respiratory consequences of PDA, such as pulmonary congestion that lead to increased work of breathing[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eLung ultrasound (LU) has emerged as a promising tool in the neonatal intensive care unit (NICU) for the assessment of lung pathology, offering a non-invasive, radiation-free, bedside option that can be repeated as needed[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. It has shown utility in conditions like respiratory distress syndrome (RDS), transient tachypnea of the newborn (TTN), and bronchopulmonary dysplasia (BPD) [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The lung ultrasound score (LUS), which quantifies the severity of B-lines and consolidations, provides a semiquantitative assessment of lung aeration and pulmonary congestion[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. This capability makes LUS particularly relevant in assessing the pulmonary effects of large PDA, (L-PDA) which often causes increased respiratory effort and oxygen requirements due to pulmonary over-circulation[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eGiven its ability to assess lung parenchymal involvement, LUS may complement echocardiography by providing direct, real-time insights into PDA-related pulmonary effects[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Additionally, LUS could potentially be used to monitor changes in pulmonary status following treatment, enhancing individualized care and improving respiratory outcomes[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Nevertheless, data on the correlation between LUS and echocardiographic markers in preterm neonates with L-PDA is limited. This study aims to evaluate the association of LUS in preterm neonates with L-PDA during immediate postnatal transition and explore its correlation with echocardiographic indicators.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design, setting, and population\u003c/h2\u003e \u003cp\u003ePreviously at our center 152 neonates born at less than 29 weeks\u0026rsquo; gestational age (GA) had LU documented for a prospective study[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], and were considered eligible for inclusion. Among these neonates, 54 neonates who had a clinical targeted neonatal echocardiography (TNE) within 24 hours of LU with documentation of PDA characteristics were included in the study. This study was approved by the Research Ethics Board of Mount Sinai Hospital.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eLung Ultrasound Procedure\u003c/h3\u003e\n\u003cp\u003eLung ultrasounds were conducted on postnatal day three using a portable ultrasound machine (Z. One PRO, Mindray North America) equipped with a high-resolution linear probe (L20-5). Infants were scanned in the supine position after remaining in this position for at least 1 hour to minimize overestimation of lung ultrasound scores (LUS) due to dependent lung areas[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eEach lung was scanned in three zones (upper anterior, lower anterior, and lateral) by personnel trained in neonatal lung ultrasound. Images were securely transferred to a password-protected external hard drive. Two expert investigators, who were blinded to clinical condition of study population, had independently calculated the LUS (total score ranging from 0\u0026ndash;18)[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] after the study's completion.\u003c/p\u003e\n\u003ch3\u003eTargeted Neonatal Echocardiography:\u003c/h3\u003e\n\u003cp\u003eOur unit has a mature, well-established TNE-based hemodynamic consultation program. Under this program, TNEs are performed either by an experienced TNE staff physician or trained sonographer or fellow under direct supervision. During the study period, all TNEs were performed with the GE E95 ultrasound machine and 12 MHz phase array probe, using our unit\u0026rsquo;s published standardized TNE imaging protocol[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. All TNEs are reported on the same day by one of the four TNE staff physicians. As a standard practice in our program, all TNE reports includes recording PDA presence and key related hemodynamic parameters indicative of shunt volume. For this study, the following parameters were recorded for all included patients from the TNE reports: PDA presence and diameter in mm, left ventricular output and the ratio of left atrial and aortic root diameter, measured using standard methodology[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e\n\u003ch3\u003eStudy Cohort Categorization\u003c/h3\u003e\n\u003cp\u003eThe definition of hemodynamically significant PDA (Hs-PDA) remains debated, with little consensus, especially during immediate postnatal period[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. While Hs-PDA scoring systems exist, they lack validation in large trials.[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. For this study, we used the pragmatic definition to divide study cohort into those with large PDA (L-PDA, defined as PDA with diameter\u0026thinsp;\u0026ge;\u0026thinsp;1.5 mm and predominantly left-to-right shunt) and those with absent or small PDA (diameter\u0026thinsp;\u0026lt;\u0026thinsp;1.5 mm).\u003c/p\u003e\n\u003ch3\u003eData collection\u003c/h3\u003e\n\u003cp\u003eStudy data were sourced from the original study database and supplemented with information from patients' electronic medical records. The dataset included demographic and clinical details such as gestational age, sex, birth weight, mode of delivery, Apgar score at 5 minutes, antenatal steroid administration, Score for Neonatal Acute Physiology with Perinatal Extension-II (SNAPPE-II) score, surfactant use, mechanical ventilation, early-onset sepsis diagnosis, lung ultrasound scores, ventilation mode, average mean airway pressure (MAP), fraction of inspired oxygen (FiO2), and respiratory severity score [RSS\u0026thinsp;=\u0026thinsp;FiO2 x MAP] at the time of the scan, and TNE data related to PDA (PDA diameter, LA: Ao, and LVO).\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eOutcomes\u003c/h2\u003e \u003cp\u003eThe primary aim of this study was to evaluate the association of LUS in detecting the presence of a L-PDA as identified by TNE. The secondary aim was to assess the correlation between LUS findings and echocardiographic indices, including PDA diameter, LA:Ao ratio, and LVO.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eBaseline demographic and outcome variables were compared between the two groups (L-PDA and No/Small PDA). Categorical variables were analyzed using the Chi-square or Fisher\u0026rsquo;s exact test, while continuous variables were evaluated with the Student\u0026rsquo;s t-test or Wilcoxon Rank-Sum test, as appropriate. Logistic regression was employed to assess the association between change in LUS and L-PDA, adjusting for GA, antenatal steroid administration, invasive mechanical ventilation (IMV), and respiratory severity score (RSS\u0026thinsp;=\u0026thinsp;fraction of inspired oxygen \u0026times; mean airway pressure) at the time of LU. For the logistic model, both unadjusted and adjusted odds ratios were calculated with L-PDA as the dependent variable and change in LUS as independent variable. The odds ratios for both change in LUS and change in RSS were calculated based on a one-point increase in the score. Pearson\u0026rsquo;s correlation coefficients were calculated to explore linear relationships between LUS, RSS, PDA diameter, LVO, and LA:Ao. All analyses were conducted using SAS software (version 9.4, SAS Institute Inc., Cary, NC), with statistical significance set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eAmong the 54 preterm neonates included in the study, 32 (59%) were identified as having L-PDA. Baseline characteristics were comparable between the L-PDA and No/Small PDA groups, with no significant differences observed in GA at birth, age at assessment, respiratory support, and RSS at the time of LU scan (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Univariate analysis revealed no statistically significant differences in LUS between the groups (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and e-Figure 1). For TNE variables, while LVO was higher in the L-PDA group, LA:Ao was similar (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic Characteristics of Study Participants\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eL-PDA\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;32)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo/small PDA\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;22)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGA at birth (wk), median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.00 (24.4, 26.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.45 (24.6, 27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.35\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirth weight (g), median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e693 (610, 885)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e775 (620, 880)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSGA, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.14*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntenatal steroids, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 (75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.22\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSNAPPE-II, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (9, 23.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (5, 14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.18\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCaesarean delivery, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (50 (11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.82\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurfactant administration, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.14*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge at assessment (week), median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.4 (24.7, 26.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.9 (25.0, 27.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.53\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBPD (moderate, severe), n %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31 (97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.01*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMortality prior to discharge, n %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.00*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRespiratory Support at the Time of Assessment\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIMV at the scan, n %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.32\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNIV at the scan, n %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.32\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMAP at the scan mean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.06 (2.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.73 (2.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.60\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFiO2 at the scan, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.26 (0.21, 0.34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.23 (0.21, 0.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRSS at scan, mean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.87 (1.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.55 (1.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.34\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eL-PDA: Large- patent ductus arteriosus; GA: gestational age; IQR: interquartile range; SGA: small for GA; SNAPPE-II: Score for Neonatal Acute Physiology with Perinatal Extension-II; BPD: bronchopulmonary dysplasia; IMV: Invasive Mechanical Ventilation; NIV: Non-invasive ventilation; MAP: Main Airway Pressure; FiO2: fraction of inspired oxygen: RSS: Respiratory severity score (=\u0026thinsp;FiO2 x MAP); SD: standard deviation.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eNotes: the reported p-values were based on the comparison between two groups using Chi-square test or Fisher\u0026rsquo;s exact test* for categorical variables and Student t test or Wilcoxon-Rank-Sum test as appropriate for continuous variables.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of LUS and Echocardiographic Indices between Groups.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eL-PDA\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;32)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo/small PDA\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;22)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLUS, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (14, 16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14.5 (11, 16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.31\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePDA diameter (mm), mean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.29 (0.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.25 (0.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLa:Ao, mean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.66 (0.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.57 (0.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLVO (ml/kg/min), mean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e287.09 (82.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e226.61 (69.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.008\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eLUS: Lung ultrasound score; PDA: Patent Ductus Arteriosus; La:Ao: left atrial-to-aortic root ratio; LVO: left ventricular output.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eThe reported p-values were based on the comparison between two groups Wilcoxon-Rank-Sum test.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eA multiple logistic regression model found no significant association between change in LUS (a one-point increment of LUS) and the presence of L-PDA (adjusted OR: 1.19; 95% CI: 0.89\u0026ndash;1.59) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). However, LUS showed a statistically significant positive correlation with RSS (r\u0026thinsp;=\u0026thinsp;0.34, p\u0026thinsp;=\u0026thinsp;0.01) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e) but not with TNE indices of LVO or LA:Ao. Additionally, PDA diameter demonstrated a weak positive correlation with RSS, that did not reach statistical significance (r\u0026thinsp;=\u0026thinsp;0.28, p\u0026thinsp;=\u0026thinsp;0.07) (e-Figure 2).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMultivariate Logistic Regression Analyses\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eOdds Ratios (95% CI) L-PDA vs no-PDA/small PDA\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUnadjusted (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAdjusted (95% CI)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLUS (one unit increase in score)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.20 (0.95, 1.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.19 (0.89, 1.59)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRSS (one unit increase in score)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.27 (0.78, 2.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.23 (0.64, 2.35)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eCI: Confidence Interval\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eAdjusted OR was based on the multiple logistic regression model adjusted for LUS, GA, IMV, RSS, and antenatal steroid.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, early LUS within the first three postnatal days was not associated with L-PDA in either univariate or multivariate analyses. Two factors may explain this finding. First, our cohort primarily consisted of extremely preterm infants (mean GA 25 weeks) with RDS, whose sonographic features (e.g., echogenic \"white lung,\" pleural line abnormalities) overlap with those of pulmonary congestion from L-PDA, potentially masking PDA-related changes.[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] Second, during the immediate postnatal transition, L-PDA may not cause significant pulmonary changes due to limited duration of exposure and low shunt volume. Thus, combining LUS with echocardiography may provide a more comprehensive evaluation of neonatal cardiorespiratory status, facilitating accurate diagnosis and management.\u003c/p\u003e \u003cp\u003eOn the other hand, our study revealed a significant positive correlation between LUS and the RSS, indicating that LUS effectively reflects respiratory disease severity. This finding underscores its potential utility in assessing pulmonary status in preterm infants, independent of PDA presence.[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] Several studies have explored the relationship between LUS and the presence of significant PDA with left-to-right shunting[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan additionalcitationids=\"CR28 CR29\" citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eYu et al[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] reported significantly higher LUS in the persistent PDA group compared to the no-PDA group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). However, direct comparison with our findings is challenging due to uncertainties regarding whether \"persistent PDA\" specifically referred to L-PDA, the inclusion of more mature neonates (GA\u0026thinsp;\u0026lt;\u0026thinsp;37 weeks), and the absence of data on respiratory status at the time of assessment. These factors make it difficult to attribute their findings solely to PDA. In a case series, Savoia et al.[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] studied five infants (birth weight: 787\u0026thinsp;\u0026plusmn;\u0026thinsp;88 grams; GA: 25.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7 weeks) who underwent PDA ligation on postnatal day 41. They reported significant reductions in LUS and LVO post-ligation. However, the small sample size limits the generalizability of their findings. Additionally, the study\u0026rsquo;s timing differs markedly from ours, as we conducted LU during the transitional period (postnatal day 3) when RDS is the predominant lung pathology, leading to similar LU patterns as seen in infants with significant PDA.\u003c/p\u003e \u003cp\u003eMartini et al.[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e] conducted daily LUS and echocardiography in 46 infants born at a median GA of 29 weeks (IQR: 27\u0026ndash;31) and found higher LUS in those with HsPDA compared to those with a restrictive or closed ductus. However, their findings did not align with ours, likely due to their inclusion of neonates with higher GA. This is a crucial distinction, as LUS is inversely related to GA, infants born before 28 weeks typically have higher LUS, primarily due to RDS, whose patterns can resemble those seen in HsPDA [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Similarly, Ozdemir et al.[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] performed LUS and echocardiography on days 1, 3, and 7 after birth in 107 infants born at GA\u0026thinsp;\u0026lt;\u0026thinsp;34 weeks and found higher LUS in HsPDA cases. As with Martini et al., their inclusion of more mature neonates (\u0026lt;\u0026thinsp;34 weeks) may explain the differences in findings. In contrast, Zong et al.[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e] prospectively studied 81 infants (median GA: 25 weeks, IQR: 24.4\u0026ndash;25.4), performing echocardiography followed by LUS on day 14. Using a 12-area scoring system (0\u0026ndash;48), they identified an LUS cutoff of 36 that predicted PDA ligation with 96% sensitivity, 86% specificity, and predictive values of 82% (positive) and 98% (negative). However, differences in scoring methods and scan timing (day 14 vs. day 3 in our study) limit direct comparison. Both our findings and those of Zong et al. align with Alonso-Ojembarrena et al.[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e], who reported that LUS progression varies with postnatal age. This highlights the dynamic nature of lung ultrasound findings over time and underscores the importance of considering postnatal age when interpreting LUS in preterm infants.\u003c/p\u003e \u003cp\u003eAlonso-Ojembarrena et al.[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e] found that LUS correlated with PDA size and left ventricular function in infants born after 28 weeks but not in those born before 28 weeks. This aligns with our findings, reinforcing that in extremely preterm neonates, early LUS primarily reflects prematurity and RDS severity rather than PDA status. In our study, both groups exhibited relatively high LUS, regardless of PDA presence, highlighting the predominant lung pathology of RDS in extremely preterm infants. This suggests that while LUS effectively detects generalized lung disease, its ability to distinguish pulmonary congestion due to L-PDA from RDS in the early transitional period is limited. Therefore, echocardiography remains essential for identifying cardiac causes of pulmonary congestion. Integrating LUS with echocardiography provides a more comprehensive assessment of neonatal cardiorespiratory status, enhancing diagnostic accuracy and guiding clinical management.\u003c/p\u003e \u003cp\u003eThis study had several limitations. First, not all data were collected prospectively, and reliance on medical records may have introduced selection and information bias. Second, the small sample size may have reduced statistical power to detect subtle associations. Third, variations in clinical management, including respiratory support and PDA treatment, could have influenced the outcomes.\u003c/p\u003e \u003cp\u003eIn conclusion, there was no association between LUS and L-PDA during the first three postnatal days in this cohort. This finding may reflect the limitations of LUS in detecting pulmonary overcirculation in the setting of RDS or the minimal impact of L-PDA (low shunt volume, short duration) on pulmonary pathology during early transition period. Future studies with larger cohorts are required to confirm these findings and further explore the clinical utility of LUS in assessing PDA.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eLU - Lung Ultrasound\u003c/p\u003e\n\u003cp\u003eLUS -Lung Ultrasound Score\u003c/p\u003e\n\u003cp\u003ePDA - patent ductus arteriosus\u003c/p\u003e\n\u003cp\u003eLA: Ao - left atrium: Aortic root ratio\u003c/p\u003e\n\u003cp\u003eLPDA- Large patent ductus arteriosus\u003c/p\u003e\n\u003cp\u003eLVO - left ventricular output\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRDS- respiratory distress syndrome\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRSS - respiratory severity score\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTNE- Targeted neonatal echocardiography\u003c/p\u003e\n\u003cp\u003eHsPDA-Hemodynamic significant patent ductus arteriosus\u003c/p\u003e\n\u003cp\u003eSNAPPE-II \u0026ndash; Score for Neonatal Acute Physiology with Perinatal Extension-II\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u0026nbsp;\u003c/strong\u003eWe would also like to thank the families and nurses in Mount Sinai Hospital who support our research program.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGuarantor:\u0026nbsp;\u003c/strong\u003eAM, who\u0026nbsp;takes responsibility for the content of the manuscript, including the data and analysis (OriginalResearch)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions:\u0026nbsp;\u003c/strong\u003eAM conceive the research idea, design the study, and manuscript writing\u003cstrong\u003e.\u0026nbsp;\u003c/strong\u003eAM had full access to all of the data and takes responsibility for the content of this manuscript, including study design, data and data analysis. The study design was conducted by AM and AJ; data collection was performed by JI. \u0026nbsp; Data analysis was performed by SL and AM. \u0026nbsp;The manuscript was prepared by AM then edited by PS, AK, NM, and AJ. \u0026nbsp;All authors of this study approved the final draft of the manuscript\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval:\u0026nbsp;\u003c/strong\u003eLocal research ethics approval was obtained (Mount Sinai Hospital REB (22-0233-C), Toronto, On, Canada. Authors certify that the study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate:\u0026nbsp;\u003c/strong\u003eNot applicable given the retrospective nature of the study\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u0026nbsp;\u003c/strong\u003eAll the authors have seen the final version of the manuscript and gave their full consent for the publication.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest:\u0026nbsp;\u003c/strong\u003eThe authors have no financial or completing conflicts of interest to declare.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eThis study was not supported by any funding sources.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eAbstract publication/presentation:\u003c/strong\u003e\u0026nbsp; Portions of this paper were presented at the 2024 Pediatric Academic Society (PAS) meeting in Toronto, Canada, as a poster presentation.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eHamrick SEG et al (2020) Patent Ductus Arteriosus Preterm Infant Pediatr, 146(5)\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSung SI et al (2019) Natural evolution of ductus arteriosus with noninterventional conservative management in extremely preterm infants born at 23\u0026ndash;28 weeks of gestation. PLoS ONE 14(2):e0212256\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eClyman RI (2018) Patent ductus arteriosus, its treatments, and the risks of pulmonary morbidity. Semin Perinatol 42(4):235\u0026ndash;242\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFowlie PW, Davis PG, McGuire W (2010) Prophylactic intravenous indomethacin for preventing mortality and morbidity in preterm infants. Cochrane Database Syst Rev 2010(7):CD000174\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSingh Y et al (2020) Echocardiographic Diagnosis and Hemodynamic Evaluation of Patent Ductus Arteriosus in Extremely Low Gestational Age Newborn (ELGAN) Infants. Front Pediatr 8:573627\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHsu KH et al (2020) Effects of Patent Ductus Arteriosus on Organ Blood Flow in Infants Born Very Preterm: A Prospective Study with Serial Echocardiography. J Pediatr 216:95\u0026ndash;100e2\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu C et al (2020) Related Factors of Patent Ductus Arteriosus in Preterm Infants: A Systematic Review and Meta-Analysis. Front Pediatr 8:605879\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKurepa D et al (2018) Neonatal lung ultrasound exam guidelines. J Perinatol 38(1):11\u0026ndash;22\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRuoss JL et al (2021) Lung Ultrasound in the Neonatal Intensive Care Unit: Does It Impact Clinical Care? Child (Basel), 8(12).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMiller LE, Stoller JZ, Fraga MV (2020) Point-of-care ultrasound in the neonatal ICU. Curr Opin Pediatr 32(2):216\u0026ndash;227\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrat R et al (2015) Lung Ultrasonography Score to Evaluate Oxygenation and Surfactant Need in Neonates Treated With Continuous Positive Airway Pressure. JAMA Pediatr 169(8):e151797\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYu LF et al (2021) Bedside cardiopulmonary ultrasonography evaluates lung water content in very low-weight preterm neonates with patent ductus arteriosus. World J Clin Cases 9(8):1827\u0026ndash;1834\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSingh Y et al (2024) \u003cem\u003eNarrative Review on Echocardiographic Evaluation of Patent Ductus Arteriosus in Preterm Infants.\u003c/em\u003e J Cardiovasc Dev Dis, 11(7)\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZong H et al (2023) The Predictive Value of Lung Ultrasound Score on Hemodynamically Significant Patent Ductus Arteriosus among Neonates =25 Weeks. Diagnostics (Basel), 13(13)\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSavoia M et al (2022) Lung ultrasound score parallels trends in systemic haemodynamics after PDA ligation: a case series. Eur J Pediatr 181(6):2541\u0026ndash;2546\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMohamed A et al (2021) Lung Ultrasound for Prediction of Bronchopulmonary Dysplasia in Extreme Preterm Neonates: A Prospective Diagnostic Cohort Study. J Pediatr 238:187\u0026ndash;192e2\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLouis D et al (2021) Prone versus Supine Position for Lung Ultrasound in Neonates with Respiratory Distress. Am J Perinatol 38(2):176\u0026ndash;181\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJain A et al (2017) Left Ventricular Function in Healthy Term Neonates During the Transitional Period. J Pediatr 182:197\u0026ndash;203e2\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcNamara PJ et al (2024) Guidelines and Recommendations for Targeted Neonatal Echocardiography and Cardiac Point-of-Care Ultrasound in the Neonatal Intensive Care Unit: An Update from the American Society of Echocardiography. J Am Soc Echocardiogr 37(2):171\u0026ndash;215\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMitra S, McNamara PJ (2020) Patent Ductus Arteriosus-Time for a Definitive Trial. Clin Perinatol 47(3):617\u0026ndash;639\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMitra S et al (2018) Association of Placebo, Indomethacin, Ibuprofen, and Acetaminophen With Closure of Hemodynamically Significant Patent Ductus Arteriosus in Preterm Infants: A Systematic Review and Meta-analysis. JAMA 319(12):1221\u0026ndash;1238\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcNamara PJ, Sehgal A (2007) Towards rational management of the patent ductus arteriosus: the need for disease staging. Arch Dis Child Fetal Neonatal Ed 92(6):F424\u0026ndash;F427\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEl-Khuffash A et al (2015) A Patent Ductus Arteriosus Severity Score Predicts Chronic Lung Disease or Death before Discharge. J Pediatr 167(6):1354\u0026ndash;1361e2\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCopetti R et al (2008) Lung ultrasound in respiratory distress syndrome: a useful tool for early diagnosis. Neonatology 94(1):52\u0026ndash;59\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSabour S (2019) Lung ultrasound in evaluating the severity of neonatal respiratory distress syndrome: Methodological issues on diagnostic value and prediction to avoid misinterpretation. Eur J Radiol 120:108663\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePang H et al (2019) Diagnostic value of lung ultrasound in evaluating the severity of neonatal respiratory distress syndrome. Eur J Radiol 116:186\u0026ndash;191\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMartini S et al (2023) Impact of patent ductus arteriosus on non-invasive assessments of lung fluids in very preterm infants during the transitional period. Eur J Pediatr 182(9):4247\u0026ndash;4251\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOzdemir M et al (2024) Lung ultrasound score in the decision of patent ductus arteriosus closure in neonates. J Clin Ultrasound 52(4):415\u0026ndash;425\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZong H et al (2023) Lung ultrasound score predicts patent ductus arteriosus ligation among neonates =25 weeks\u0026lt;/at. Pediatr Pulmonol 58(9):2487\u0026ndash;2494\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlonso-Ojembarrena A (2023) P.d.M.U.H., San Fernando, Andalucia, Spain; Pamela Zafra-Rodriguez, \u003cem\u003eRelationship between lung ultrasound scores and echocardiographic measurements in very low birth weight infants.\u003c/em\u003e PAS 2023. 126\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlonso-Ojembarrena A et al (2022) Lung Ultrasound Scores Progress Differently in Extreme and Very Preterm Infants after Birth: A Multicentre Prospective Study. Neonatology 119(5):558\u0026ndash;566\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejpe","sideBox":"Learn more about [European Journal of Pediatrics](https://www.springer.com/journal/431)","snPcode":"431","submissionUrl":"https://submission.nature.com/new-submission/431/3","title":"European Journal of Pediatrics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Neonates, Lung ultrasound, Echocardiography, Patent ductus arteriosus, Preterm infant.","lastPublishedDoi":"10.21203/rs.3.rs-6258106/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6258106/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Recent studies suggested lung ultrasound (LU) as a useful, non-invasive bedside tool for assessing pulmonary edema; however, its utility in identifying preterm neonates with large patent ductus arteriosus (L-PDA) is limited.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjective:\u003c/strong\u003e To evaluate the association of LU score (LUS) in preterm neonates with L-PDA during the transitional period and explore correlation of LUS with echocardiographic indicators.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eAmong 152 neonates born \u0026lt; 29 weeks’ gestation and had LU performed at day-of-life (DOL) three for a previous prospective study, 54 neonates had concomitant echocardiography documenting PDA presence, diameter, and variables for shunt volume. We included in the analysis neonates who had LU and Echo on DOL 3. Neonates with L-PDA were compared to those with absent or small PDA. Univariate, multivariate, and Pearson’s correlation coefficients analyses were conducted.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eOf the 54 infants included in the study, 32 (59%) were diagnosed with L-PDA. There were no significant differences in baseline characteristics between the L-PDA and no-L-PDA group. Univariate analysis showed no association between LUS and L-PDA. Similarly, multivariate analysis found that a one-point increment of LUS was not associated to L-PDA (adjusted OR: 1.19; 95% CI: 0.89–1.59). LUS demonstrated a significant correlation with respiratory severity score and a weak correlation with PDA diameter, but no significant associations with other PDA shunt volume variables.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e In this cohort, LUS was not associated with L-PDA during the transition period. Larger studies are required to confirm these findings and further explore the clinical utility of LUS in assessing PDA.\u003c/p\u003e","manuscriptTitle":"Association of Lung Ultrasound score with Large Patent Ductus Arteriosus in Preterm Neonates during the transitional period","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-23 05:33:18","doi":"10.21203/rs.3.rs-6258106/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-04-16T12:20:53+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-14T20:04:42+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-08T19:28:31+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"191786196465824243941797561901997372372","date":"2025-03-29T17:59:48+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"86495839119426905955223620925880464235","date":"2025-03-29T16:12:39+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-03-29T16:03:40+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-03-24T10:22:04+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-03-24T10:10:37+00:00","index":"","fulltext":""},{"type":"submitted","content":"European Journal of Pediatrics","date":"2025-03-19T05:22:56+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejpe","sideBox":"Learn more about [European Journal of Pediatrics](https://www.springer.com/journal/431)","snPcode":"431","submissionUrl":"https://submission.nature.com/new-submission/431/3","title":"European Journal of Pediatrics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"7fc9afe6-e3d8-4e09-a0e5-66b874fb52b8","owner":[],"postedDate":"April 23rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-05-26T16:00:48+00:00","versionOfRecord":{"articleIdentity":"rs-6258106","link":"https://doi.org/10.1007/s00431-025-06186-6","journal":{"identity":"european-journal-of-pediatrics","isVorOnly":false,"title":"European Journal of Pediatrics"},"publishedOn":"2025-05-20 15:57:27","publishedOnDateReadable":"May 20th, 2025"},"versionCreatedAt":"2025-04-23 05:33:18","video":"","vorDoi":"10.1007/s00431-025-06186-6","vorDoiUrl":"https://doi.org/10.1007/s00431-025-06186-6","workflowStages":[]},"version":"v1","identity":"rs-6258106","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6258106","identity":"rs-6258106","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}