Lung Ultrasound Scoring-Driven Precision: A Non-Invasive Paradigm for Optimal Surfactant Timing in Neonatal Meconium Aspiration Syndrome | 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 Lung Ultrasound Scoring-Driven Precision: A Non-Invasive Paradigm for Optimal Surfactant Timing in Neonatal Meconium Aspiration Syndrome Qi Chen, Lei Cao, wei xiong, Zekai Yu, Maohua Wu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6257579/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Meconium aspiration syndrome (MAS) is a severe respiratory disease in neonates, and the timing of the application of pulmonary surfactant (PS) is still controversial. Lung ultrasound (LUS), as a non-invasive, highly sensitive and specific imaging technique, may provide a basis for the precise use of PS. Methods This study was a prospective observational study, and 218 MAS infants from two tertiary neonatal rescue centers were included. The LUS score (total score of 18 points, divided into 6 zones) was compared with traditional indicators (oxygenation index, oxygen concentration, etc.), and the ROC curve was used to analyze the predictive efficiency. Results When the LUS score threshold was 5.5 points (actually 6 points), the AUC for predicting the timing of PS use was 0.9886 (95% CI: 0.9967-1), with a sensitivity of 99% and a specificity of 98%, which was significantly better than the oxygenation index (AUC = 0.9673), oxygen concentration (AUC = 0.9527) and pH value (AUC = 0.9062). LUS is non-invasive and repeatable, and can reduce complications (such as PPHN) and hospital stay. Conclusion LUS score ≥ 6 is a reliable indicator for initiating PS treatment in children with MAS, which can optimize the timing of treatment and improve clinical prognosis. Neonatal meconium aspiration syndrome lung ultrasound pulmonary surfactant neonatal intensive care unit lung ultrasound score Figures Figure 1 What is Known – What is New This study addresses the limitations of traditional invasive metrics, which are associated with high complications and costs, by establishing the LUS score (≥6) as a highly sensitive and specific indicator (AUC=0.9886) for precise PS initiation. Results show that LUS enables dynamic monitoring, optimizing PS use, reducing complications, and shortening hospital stays, with predictive accuracy surpassing traditional parameters. Its non-invasive, cost-effective nature promotes standardized clinical care, offering an innovative approach to personalized treatment and resource optimization. 1. INTRODUCTION Meconium aspiration syndrome(MAS) is one of the common diseases of newborns. It is also a clinical disease characterized by respiratory attenuation that is more serious in near-term or full-term infants and post-term infants. Its accompanying complications are also a major challenge for clinicians 1 . Early diagnosis and early treatment are particularly critical. The use of pulmonary surfactant (PS) in MAS is a routine means of treating severe cases 2,3 , but there is still controversy and inconsistent standards on when to use PS. The Canadian Pediatric Society recommends 4 that PS should be used for all children with endotracheal intubation and oxygen concentration greater than 50%. China uses it for children with an oxygenation index(OI) greater than 8 5 . Natural PS is expensive, and its use should be rational. In MAS, a reliable predictive indicator is needed to evaluate the use of PS in MAS, which can not only help clinicians advance the window period for using PS, reduce the occurrence of complications, and shorten the overall hospitalization time, but also avoid abusing PS and causing an increase in overall hospitalization costs.Lung ultrasound is an emerging imaging technology in recent years 6–8 . It has high specificity and sensitivity for the diagnosis of various lung diseases 9,10 , including MAS, and is increasingly favored by clinicians for its radiation-free and convenient bedside 11 . The predictive role of lung ultrasound in Neonatal respiratory distress syndrome has been confirmed 12–21 . Lung ultrasound scores have a predictive effect on the timing of PS use in MAS with high sensitivity. This study aimed to explore the predictive value of Lung ultrasound (LUS) scores for the timing of PS use in children with MAS. Early intervention plays a crucial role in mitigating long-term developmental impairments in neonates with severe respiratory conditions, such as MAS. Delayed or inappropriate treatment may lead to persistent pulmonary hypertension (PPHN), prolonged mechanical ventilation, and an increased risk of neurodevelopmental delays. 2. MATERIALS AND METHODS 2.1Ethical considerations and data privacy This study was a prospective observational study conducted in two academic, tertiary centers for the treatment of severe neonates. Ethical approval was obtained from the ethics committees and review bodies of both centers. All parents of the newborns gave informed consent and signed the informed consent form. All authors supported the study protocol and decided to co-publish. 2.2Study subjects This study collected data from 512 full-term newborns (gestational age 37–42 weeks) from 2 critical neonatal rescue centers between 2019 and 2024. And newborns with clear amniotic fluid III° contamination after rupture of membranes or during delivery, inclusion criteria: MAS infants with gestational age 37–42 weeks, amniotic fluid III contamination and requiring NICU treatment (n = 218) 22 . Exclusion criteria: those with good birth conditions and mother-baby rooming-in (n = 294). Clinical details were recorded as part of the study, including detailed information such as gestational age, gender, hospitalization status, and the presence or absence of complications. For children admitted to the NICU for treatment, two clinicians who are proficient in bedside ultrasound and have obtained relevant qualifications performed lung ultrasound examinations within half an hour after admission to score the lung conditions. (Pulmonary ultrasound scoring method and details: The lungs are usually divided into 6 areas with the two nipples as the connecting line. Each area is scored with a score of 0–3 points, for a total of 18 points. The higher the score, the more serious the condition. 23 ) Both doctors were unaware of the study before the conclusions were announced. 2.3Lung ultrasound score The ultrasound appearance of each area is usually divided into 4 levels. 0 points: normal ventilation, visible lung sliding with A lines or a small number of (less than 2 separate) B lines. 1 point: reduced lung ventilation, more than 3 B lines, and there are spaces between the B lines without fusion. 2 points: severely reduced lung ventilation, fused B lines, with or without small subpleural consolidation. 3 points: lung consolidation, a wide range of tissue changes. 2.4Interventions At the same time, we recorded the X-ray grade rating, oxygen concentration, OI, and Ph value in the electronic file. The decision on whether to use PS 24,25 was based on the oxygen concentration threshold (> 50%) combined with the OI index. The lung ultrasound score did not guide the treatment of PS. All data were recorded and analyzed anonymously and used only for research purposes. The ROC curve was used to analyze the predictive efficacy of each indicator for the timing of PS use, and the threshold was determined by the maximum Youden index. 2.5Statistical Design and Data Analysis Methodology 2.5.1Statistical design and sample size rationality This study used G*Power 3.1 software to conduct a priori statistical power analysis (α = 0.05, Power = 0.8). Based on preliminary experimental data, assuming that the difference in the area under the receiver operating characteristic curve (AUC) of lung ultrasound (LUS) scores and traditional OI is 0.1, the minimum sample size was calculated to be 200 cases. Finally, 218 children with meconium aspiration syndrome (MAS) were included, meeting the statistical power requirements. 2.5.2Lung ultrasound scoring and operator consistency Lung ultrasound examinations were performed by two independent neonatologists (qualified to perform neonatal LUS) using a blind evaluation method (the operators were unaware of the clinical intervention plan and research hypothesis of the children). To verify inter-rater reliability, ultrasound images of 30 children were randomly selected for double-blind re-evaluation, and Fleiss' Kappa coefficient was used to evaluate classification consistency (κ = 0.85, 95% CI: 0.76–0.94), indicating that the scoring criteria were highly reproducible. 2.5.3Control of confounding variables and statistical modeling To exclude the interference of potential confounding factors (gestational age, persistent pulmonary hypertension [PPHN], etc.) on the results, a multivariate logistic regression model was used for correction analysis. Pulmonary surfactant (PS) use was used as the dependent variable, LUS score was used as the core independent variable, gestational age (weeks), birth weight (g), and PPHN incidence were included as covariates, and the adjusted odds ratio (Adjusted OR) and 95% confidence interval were calculated. All statistical analyses were completed using SPSS 26.0, continuous variables were expressed as mean ± standard deviation, and the Mann-Whitney U test was used for comparison between groups. Bilateral P < 0.05 was considered statistically significant. 2.6Data analysis ROC curve showed that among the indicators of MAS using PS, the lung ultrasound score threshold was 5.5, the sensitivity was 99%, the specificity was 98%, the accuracy was 99%, and the area under the ROC curve (AUC) was 0.9886 (95% Cl: 0.9967-1, P < 0.05). The pH value threshold was 7.14, the sensitivity was 70%, the specificity was 91%, the accuracy was 83%, and the area under the ROC curve (AUC) was 0.9062 (95% Cl: 0.8676–0.9448, P < 0.05). The oxygen concentration threshold was 47.5, the sensitivity was 85%, the specificity was 91%, the accuracy was 88%, and the area under the ROC curve (AUC) was 0.9527 (95% Cl: 0.9304–0.9751, P < 0.05). The OI threshold was 7.5, the sensitivity was 91%, the specificity was 99%, the accuracy was 94%, and the area under the ROC curve (AUC) was 0.9673 (95% Cl: 0.9408–0.9938, P 0.2). 2.7Statistical analysis Continuous variables were expressed as mean ± standard deviation and compared using the Mann-Whitney U test. Receiver operating curves were used to analyze the predictive value of lung ultrasound scores, pH, oxygen concentration, and OI for PS. Statistical analysis was performed using SPSS version 26.0 (IBM Corp, Armonk, New York, USA). A two-sided P < 0.05 was considered statistically significant. 3. RESULTS During the study period, we included a total of 218 children with MAS. Table 1 provides the basic information of the experimental children and the research data of the children when PS was used. Figure 1 shows that the maximum curve area was achieved when the lung ultrasound score was greater than 6 points (threshold 5.5), and the sensitivity and accuracy were significantly better than other indicators (Table 2), and the specificity was slightly lower than the OI (98%/100%). The hospitalization time of children in the LUS group was shorter than that in the traditional indicator group (p < 0.05), and the use rate of PPHN and ECMO was significantly reduced. Considering that the OI requires blood gas analysis and other invasive operations, ultrasound has the advantages of non-invasiveness, convenience, and repeatability. We still believe that ultrasound scoring is suitable for evaluating the timing of PS use in MAS. Table 1 Variables No.Pts Non-Invasive Ventilation, (NIV) No.Pts Invasive Mechanical Ventilation(IMV) P values Gestational age 138 39.84 ± 1.58 80 39.95 ± 1.41 0.574 Lung ultrasound score 138 4.02 ± 0.99 80 8.79 ± 2.24 < 0.001 Grade of chest film 138 2.43 ± 0.53 80 2.51 ± 0.50 0.272 Fraction of inspiration 138 34.11 ± 8.75 80 52.94 ± 6.64 < 0.001 pH 138 7.21 ± 0.07 80 7.07 ± 0.09 < 0.001 Oxygenation Index 56 6.59 ± 0.53 80 10.17 ± 1.80 < 0.001 Hospital stay 138 6.31 ± 1.18 80 8.15 ± 1.30 0.013 Table 2 Variables Threshold Specificity Sencitivity Accuracy Lung ultrasound score 5.5 0.986 0.999 0.991 Fraction of inspiration 47.5 0.913 0.85 0.89 pH 0.14 0.913 0.7 0.835 Oxygenation Index 7.5 0.999 0.913 0.949 4. DISCUSSION We have proved that lung ultrasound scoring does have a guiding role in MAS 26,27 . On the one hand, lung ultrasound scoring can be used to determine the lung condition, thereby guiding clinicians to use PS as early as possible to avoid serious complications such as persistent pulmonary hypertension (PPHN) and extracorporeal membrane oxygenation (ECMO). On the other hand, since natural PS is expensive, lung ultrasound scoring can also avoid the economic pressure caused by excessive medical treatment. LUS can be used to accurately determine the timing of PS use and has shown obvious advantages. First of all, we need to understand that the purpose of using PS is to reduce the occurrence of complications 28,29 , reduce hospitalization time and reverse lung conditions as soon as possible. From the existing data, even the combined diagnosis (oxygen concentration combined with oxygenation index) is still less sensitive than lung ultrasound. Secondly, all other indicators currently known need to be performed under invasive operations. For children with severe MAS and PPHN, it is undoubtedly a major blow. The advantages of ultrasound are self-evident. Secondly, MAS in full-term infants is a pathophysiological feature formed by multiple factors. Multiple factors can inactivate PS 30 , including chemical and physical inflammatory stimuli; meconium blocks the airway, and partial blockage can produce a valve-like effect, leading to uneven lung expansion; meconium fatty acids can directly act on alveolar type II cells to produce toxic effects, changing the viscosity and ultrastructure of pulmonary surfactant, etc. 31 . Since meconium inhalation is not uniform, treatment mostly adopts a general and broad model. LUS can evaluate which area has more severe lesions and guide treatment more accurately and targetedly. Thirdly, LUS can dynamically track the condition of lung lesions after using PS 32 , predicting or advancing the treatment time window for severe complications. LUS determines the condition of the lungs through ultrasound artifacts, and can determine the change of the condition through lung ultrasound scores and direct lung ventilation imaging, and evaluate whether PS needs to be used again and guide weaning. Fourth, early changes in lung compliance and the promotion of meconium excretion are the key to treating MAS. Ventilation strategies and the use of ECMO can be achieved through LUS. In the treatment of MAS, LUS has great advantages 33 . The advantages of LUS in clinical practice are well known. Its advantages such as no radiation, rapidity, and convenience are suitable for NICU, especially for critically ill newborns34. The purpose of our study is to use LUS to standardize the treatment of MAS and standardize the use of PS and ventilation strategies according to the severity of the child's condition. Since the remaining indicators included in the study almost require invasive operations, this seems to be unfriendly to children with MAS who may have PPHN, and the accuracy and sensitivity are inferior to LUS. Neonatal diseases develop rapidly. Most of the late complications of improper early MAS treatment are very difficult. The key to treatment is for clinicians to quickly identify and grasp the characteristics of the disease. LUS can help clinicians better identify the disease and guide the treatment plan 35,36 , which is different from the "organic" examination preferred by ultrasound doctors 37 . Under the guidance of LUS, the hospitalization time of children is significantly shortened compared with traditional treatment. Medical resources are saved. LUS is accurate and reliable in determining MAS. The typical ultrasound evidence of MAS can be used for reference: 1. Pulmonary consolidation with bronchial inflation (irregular or jagged shadows of varying sizes at the boundary of the consolidation area). 2. Abnormal pleural line (thickening, rupture or blur). 3. B-lines or alveolar-interstitial syndrome (AIS) can be seen in non-consolidation areas. 4. Pleural effusion. 5. Atelectasis 38 . Finally, the choice of probe is preferred. Linear probe is preferred. Since most MAS are near-term or full-term infants or overdue infants, high-frequency probes are not penetrating enough, and the frequency can be reduced or replaced with a linear array probe with a slightly lower frequency. However, since a considerable number of diseases treated in NICU are premature infants, the probe frequency can now be selected from 9-14MHz to adapt to more diseases. 5. CONCLUSION LUS score ≥ 6 is a reliable indicator for initiating PS treatment in children with MAS, which can advance the treatment window, reduce complications and shorten hospitalization time. It is recommended to incorporate LUS into the standardized diagnosis and treatment process of MAS to improve clinical decision-making efficiency. Declarations All authors declare no conflicts of interest and agree to the publication of this study. For access to the raw data, please contact the corresponding author. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors Details of Ethical Approval This study has been approved by the Ethics Committee of Shangrao Maternal and Child Health Hospital, with the ethical approval number SRFB20231206037 , dated December 6, 2023. The contact address of the Ethics Committee is Shangrao Maternal and Child Health Hospital, No. 55 Shangrao Avenue, Xinzhou District, Shangrao City, Jiangxi Province, China. The contact telephone number is 0793-8209562 ( Please refer to the supplementary materials for the original ethics review document, which has been uploaded. ) This study strictly adheres to the Declaration of Helsinki and relevant ethical guidelines, ensuring the full protection of participants' rights to informed consent, privacy, and data security. All participants signed informed consent forms upon admission, clearly understanding the purpose, procedures, potential risks, and benefits of the study. No unnecessary risks or harm were imposed on participants during the research process. Author Contribution Qi Chen: Conceptualization; Investigation; Software; Formal analysis; Writing - review & editing. Lei Cao: Conceptualization; Methodology; Investigation. Wei Xiong: Conceptualization; Investigation; Writing - original draft; Writing - review & editing; Methodology; Validation; Software; Formal analysis. Zekai Yu:Conceptualization; Investigation; Formal analysis; Methodology. MaoHua Wu: Conceptualization; Investigation; Software. References Shaikh, M, Irfan Waheed, KA, Javaid, S, Gul, R, Hashmi, MA, Fatima, ST. Detrimental Complications Of Meconium Aspiration Syndrome And Their Impact On Outcome. J Ayub Med Coll Abbottabad. 2016-01-01; 28 (3): 506-509. PMID: 28712223. Stevens, TP, Harrington, EW, Blennow, M, Soll, RF. Early surfactant administration with brief ventilation vs. selective surfactant and continued mechanical ventilation for preterm infants with or at risk for respiratory distress syndrome. Cochrane Database Syst Rev. 2007-10-17; (4): CD003063. doi: 10.1002/14651858.CD003063.pub3. PMID: 17943779. Sweet, DG, Carnielli, V, Greisen, G, Hallman, M, Ozek, E, Te Pas, A, Plavka, R, Roehr, CC, Saugstad, OD, Simeoni, U, Speer, CP, Vento, M, Visser, GHA, Halliday, HL. European Consensus Guidelines on the Management of Respiratory Distress Syndrome - 2019 Update. NEONATOLOGY. 2019-01-01; 115 (4): 432-450. doi: 10.1159/000499361. PMID: 30974433. Recommendations for neonatal surfactant therapy. PAED CHILD HEALT-CAN. 2005-02-01; 10 (2): 109-16. PMID: 19668609. Willson, DF, Jiao, JH, Bauman, LA, Zaritsky, A, Craft, H, Dockery, K, Conrad, D, Dalton, H. Calf's lung surfactant extract in acute hypoxemic respiratory failure in children. CRIT CARE MED. 1996-08-01; 24 (8): 1316-22. doi: 10.1097/00003246-199608000-00008. PMID: 8706485. Singh, Y, Dauengauer-Kirliene, S, Yousef, N. Setting the Standards: Neonatal Lung Ultrasound in Clinical Practice. Diagnostics (Basel). 2024-07-02; 14 (13): doi: 10.3390/diagnostics14131413. PMID: 39001302;. Yousef, N, Piastra, M, Brat, R, Manzoni, P, Mokhtari, M, Tissieres, P, De Luca, D. PO-0774 Lung Ultrasound Findings In Meconium Aspiration Syndrome ARCH DIS CHILD. 2014-10-01; 99 (Suppl 2): A508.3-A509. doi: 10.1136/archdischild-2014-307384.1413. Wu, J, Su, C, Mao, Y. The value of lung ultrasound in the differential diagnosis of common lung diseases in newborns. MEDICINE. 2024-11-08; 103 (45): e40459. doi: 10.1097/MD.0000000000040459. PMID: 39533624. Yousef, N. [Lung ultrasound in the newborn]. ARCH PEDIATRIE. 2016-03-01; 23 (3): 317-21. doi: 10.1016/j.arcped.2015.12.001. PMID: 26879968. Guideline on lung ultrasound to diagnose pulmonary diseases in newborn infants]. Zhongguo Dang Dai Er Ke Za Zhi. 2019-02-01; 21 (2): 105-113. PMID: 30782270. Lichtenstein, DA, Mauriat, P. Lung Ultrasound in the Critically Ill Neonate. CURR PEDIATR REV. 2012-08-01; 8 (3): 217-223. doi: 10.2174/157339612802139389. PMID: 23255876. De Martino L, Yousef N, Ben-Ammar R, Raimondi F, Shankar-Aguilera S, De Luca D. Lung Ultrasound Score Predicts Surfactant Need in Extremely Preterm Neonates. Pediatrics. 2018 Sep;142(3):e20180463 . doi: 10.1542/peds.2018-0463. PMID: 30108142. Bao, LY, Dao, XY, Du, K. Progress in the Application of Lung Ultrasound for the Evaluation of Neonates with Respiratory Distress Syndrome. J Multidiscip Healthc. 2024-01-01; 17 1-9. doi: 10.2147/JMDH.S442464. PMID: 38192739. Singh, Y, Tissot, C, Fraga, MV, Yousef, N, Cortes, RG, Lopez, J, Sanchez-de-Toledo, J, Brierley, J, Colunga, JM, Raffaj, D, Da Cruz, E, Durand, P, Kenderessy, P, Lang, HJ, Nishisaki, A, Kneyber, MC, Tissieres, P, Conlon, TW, De Luca, D. International evidence-based guidelines on Point of Care Ultrasound (POCUS) for critically ill neonates and children issued by the POCUS Working Group of the European Society of Paediatric and Neonatal Intensive Care (ESPNIC). CRIT CARE. 2020-02-24; 24 (1): 65. doi: 10.1186/s13054-020-2787-9. PMID: 32093763. Corsini, I, Parri, N, Gozzini, E, Coviello, C, Leonardi, V, Poggi, C, Giacalone, M, Bianconi, T, Tofani, L, Raimondi, F, Dani, C. Lung Ultrasound for the Differential Diagnosis of Respiratory Distress in Neonates. NEONATOLOGY. 2019-01-01; 115 (1): 77-84. doi: 10.1159/000493001. PMID: 30304736. Dong, J, Deng, Y, Tong, J, Du, T, Liu, W, Guo, Y. The diagnostic value and efficacy evaluation of lung ultrasound score in neonatal respiratory distress syndrome: a prospective observational study. Front Pediatr. 2025-01-01; 13 1500500. doi: 10.3389/fped.2025.1500500. PMID: 39950156. Szymański, P, Kruczek, P, Hożejowski, R, Wais, P. Modified lung ultrasound score predicts ventilation requirements in neonatal respiratory distress syndrome. BMC Pediatr. 2021-01-06; 21 (1): 17. doi: 10.1186/s12887-020-02485-z. PMID: 33407270. Chan, B, Torsitano, C, Gordon, S, Konana, O, Singh, Y. Substantiating and Adopting Lung Ultrasound Scores to Predict Surfactant Need in Preterm Neonates with Respiratory Distress Syndrome within an Institution. AM J PERINAT. 2024-09-01; 41 (12): 1652-1659. doi: 10.1055/s-0044-1779500. PMID: 38346693; Gupta, D, Priyadarshi, M, Chaurasia, S, Singh, P, Basu, S. Lung ultrasound for prediction of surfactant requirement in Indian preterm neonates: a diagnostic accuracy study. EUR J PEDIATR. 2024-08-01; 183 (8): 3599-3606. doi: 10.1007/s00431-024-05626-z. PMID: 38829378. Aldecoa-Bilbao, V, Balcells-Esponera, C, Herranz Barbero, A, Borràs-Novell, C, Izquierdo Renau, M, Iriondo Sanz, M, Salvia Roigés, M. Lung ultrasound for early surfactant treatment: Development and validation of a predictive model. PEDIATR PULM. 2021-02-01; 56 (2): 433-441. doi: 10.1002/ppul.25216. PMID: 33369257. Raimondi, F, Migliaro, F, Corsini, I, Meneghin, F, Dolce, P, Pierri, L, Perri, A, Aversa, S, Nobile, S, Lama, S, Varano, S, Savoia, M, Gatto, S, Leonardi, V, Capasso, L, Carnielli, VP, Mosca, F, Dani, C, Vento, G, Lista, G. Lung Ultrasound Score Progress in Neonatal Respiratory Distress Syndrome. PEDIATRICS. 2021-04-01; 147 (4): doi: 10.1542/peds.2020-030528. PMID: 33688032. Saint-Fleur, AL, Alcalá, HE, Sridhar, S. Outcomes of neonates born through meconium-stained amniotic fluid pre and post 2015 NRP guideline implementation. PLoS One. 2023-01-01; 18 (8): e0289945. doi: 10.1371/journal.pone.0289945. PMID: 37561740. Kelner, J, Moote, D, Shah, R, Anuar, A, Golioto, A. Lung Ultrasound Score for Prediction of Surfactant Administration in Preterm Infants with Respiratory Failure. J PERINATOL. 2024-09-01; 44 (9): 1258-1263. doi: 10.1038/s41372-024-02090-3. PMID: 39122885. Brat, R, Yousef, N, Klifa, R, Reynaud, S, Shankar Aguilera, S, De Luca, D. Lung Ultrasonography Score to Evaluate Oxygenation and Surfactant Need in Neonates Treated With Continuous Positive Airway Pressure. JAMA PEDIATR. 2015-08-01; 169 (8): e151797. doi: 10.1001/jamapediatrics.2015.1797. PMID: 26237465. El Shahed, AI, Dargaville, PA, Ohlsson, A, Soll, R. Surfactant for meconium aspiration syndrome in term and late preterm infants. Cochrane Database Syst Rev. 2014-12-14; (12): CD002054. doi: 10.1002/14651858.CD002054.pub3. PMID: 25504256. Piastra, M, Yousef, N, Brat, R, Manzoni, P, Mokhtari, M, De Luca, D. Lung ultrasound findings in meconium aspiration syndrome. EARLY HUM DEV. 2014-09-01; 90 Suppl 2 S41-3. doi: 10.1016/S0378-3782(14)50011-4. PMID: 25220126. Yeh, TF, Harris, V, Srinivasan, G, et al. Roentgenographic findings in infants with meconium aspiration syndrome. JAMA-J AM MED ASSOC. 1979; 242 (1): 60-3. PMID: 448867. Dargaville, PA, Mills, JF. Surfactant therapy for meconium aspiration syndrome: current status. DRUGS. 2005-01-01; 65 (18): 2569-91. doi: 10.2165/00003495-200565180-00003. PMID: 16392874. Jobe, AH. Commentary on surfactant treatment of neonates with respiratory failure and group B streptococcal infection PEDIATRICS. 2000-11-01; 106 (5): 1135. doi: 10.1542/peds.106.5.1135. PMID: 11061786. Vain, NE, Batton, DG. Meconium "aspiration" (or respiratory distress associated with meconium-stained amniotic fluid?). SEMIN FETAL NEONAT M. 2017-08-01; 22 (4): 214-219. doi: 10.1016/j.siny.2017.04.002. PMID: 28411000. Schrama, AJ, de Beaufort, AJ, Sukul, YR, Jansen, SM, Poorthuis, BJ, Berger, HM. Phospholipase A2 is present in meconium and inhibits the activity of pulmonary surfactant: an in vitro study. ACTA PAEDIATR. 2001-04-01; 90 (4): 412-6. PMID: 11332933. Arayici, S, Sari, FN, Kadioglu Simsek, G, Yarci, E, Alyamac Dizdar, E, Uras, N, Canpolat, FE, Oguz, SS. Lung Lavage with Dilute Surfactant vs. Bolus Surfactant for Meconium Aspiration Syndrome. J TROP PEDIATRICS. 2019-10-01; 65 (5): 491-497. doi: 10.1093/tropej/fmy081. PMID: 30690595. Bendapudi, P, Rao, GG, Greenough, A. Diagnosis and management of persistent pulmonary hypertension of the newborn. PAEDIATR RESPIR REV. 2015-06-01; 16 (3): 157-61. doi: 10.1016/j.prrv.2015.02.001. PMID: 25765845. Volpicelli, G, Elbarbary, M, Blaivas, M, Lichtenstein, DA, Mathis, G, Kirkpatrick, AW, Melniker, L, Gargani, L, Noble, VE, Via, G, Dean, A, Tsung, JW, Soldati, G, Copetti, R, Bouhemad, B, Reissig, A, Agricola, E, Rouby, JJ, Arbelot, C, Liteplo, A, Sargsyan, A, Silva, F, Hoppmann, R, Breitkreutz, R, Seibel, A, Neri, L, Storti, E, Petrovic, T. International evidence-based recommendations for point-of-care lung ultrasound. INTENS CARE MED. 2012-04-01; 38 (4): 577-91. doi: 10.1007/s00134-012-2513-4. PMID: 22392031. Corsini, I, Parri, N, Ficial, B, Dani, C. Lung ultrasound in the neonatal intensive care unit: Review of the literature and future perspectives. PEDIATR PULM. 2020-07-01; 55 (7): 1550-1562. doi: 10.1002/ppul.24792. PMID: 32339409. Firszt, O, Grabowska, A, Saran, A, Kluczewska, E. Implementation of a standardized lung ultrasound protocol for respiratory distress in a neonatal intensive care unit: an observational study. J PERINATOL. 2024-09-01; 44 (9): 1264-1268. doi: 10.1038/s41372-024-01900-y. PMID: 38361003. 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. 2021-09-01; 90 (3): 524-531. doi: 10.1038/s41390-018-0114-9. PMID: 30127522. Bouhemad, B, Zhang, M, Lu, Q, Rouby, JJ. Clinical review: Bedside lung ultrasound in critical care practice. CRIT CARE. 2007-01-01; 11 (1): 205. doi: 10.1186/cc5668. PMID: 17316468; Additional Declarations No competing interests reported. Supplementary Files SupplementaryMaterialforReviewnotforpublication.docx Cite Share Download PDF Status: Posted Version 1 posted 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. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-6257579","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":440217186,"identity":"1d3aced5-14e7-41ff-bb64-bb9894ca7d0f","order_by":0,"name":"Qi Chen","email":"","orcid":"","institution":"Shangrao City Critical Neonatal Treatment Center,shangrao children's hospital","correspondingAuthor":false,"prefix":"","firstName":"Qi","middleName":"","lastName":"Chen","suffix":""},{"id":440217187,"identity":"3dabb95f-0bf4-4034-b2c9-1d48c2f3cacc","order_by":1,"name":"Lei Cao","email":"","orcid":"","institution":"The First People's Hospital of jingdezhen","correspondingAuthor":false,"prefix":"","firstName":"Lei","middleName":"","lastName":"Cao","suffix":""},{"id":440217188,"identity":"fa998c14-544f-48f7-b894-96a26d536279","order_by":2,"name":"wei xiong","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8klEQVRIie3QsUrEMBzH8X/IkS5/z7VHxWf4uxx3UM5X8ShkcnCSG/8i1MUHuMGHuEdoDaZLcM4giAhODhkdBG11cWrrJpjvkOn3ISQAsdifTHAVNvkBgAIIlK/GkIt66zR2RGzPdDHmGmn2SvNFJIZbwUN7ai65JRKpsTrLqZKQmLtdL3E11zf3Cslpm53SwxRQa99H5n7N1es5IvmkbMmLhBTn/eTxiStU6TdZkBE8SLzgGktqibIZjCHHbs3tJ5/gzOlieU26UENvmV01zyFsPg6njT3yb+/5aj8xtpf8bJJ2pxo775LhN+tYLBb7P30Cn29ROtZBGSsAAAAASUVORK5CYII=","orcid":"","institution":"Shangrao Critical Neonatal Treatment Center","correspondingAuthor":true,"prefix":"","firstName":"wei","middleName":"","lastName":"xiong","suffix":""},{"id":440217192,"identity":"013a3db9-da51-46b6-8c31-ff3e5ec1c46f","order_by":3,"name":"Zekai Yu","email":"","orcid":"","institution":"Hangzhou Dianzi University","correspondingAuthor":false,"prefix":"","firstName":"Zekai","middleName":"","lastName":"Yu","suffix":""},{"id":440217195,"identity":"7295b205-6ea4-418e-ae79-0c35ff7aebb6","order_by":4,"name":"Maohua Wu","email":"","orcid":"","institution":"Department of Ultrasound Medicine, Shangrao Maternal and Child Health Hospital","correspondingAuthor":false,"prefix":"","firstName":"Maohua","middleName":"","lastName":"Wu","suffix":""}],"badges":[],"createdAt":"2025-03-19 03:53:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6257579/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6257579/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":81014665,"identity":"d1397cd3-7111-4137-8d24-96228b5b658d","added_by":"auto","created_at":"2025-04-21 08:43:23","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":29030,"visible":true,"origin":"","legend":"\u003cp\u003eThe ROC curve shows that the LUS score has the best predictive effect on the timing of PS use (AUC=0.9886).\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6257579/v1/fcffdeb96d50d2166d6d06a6.jpg"},{"id":84390336,"identity":"b2e1ae65-741f-4874-8508-d27a17926523","added_by":"auto","created_at":"2025-06-11 11:17:05","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":790322,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6257579/v1/bd73db69-35a4-438c-a201-f7ac4ccbf5aa.pdf"},{"id":81014666,"identity":"ecf4eade-cb1f-40ae-8c13-b25b4ea5cbb8","added_by":"auto","created_at":"2025-04-21 08:43:23","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":26597,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryMaterialforReviewnotforpublication.docx","url":"https://assets-eu.researchsquare.com/files/rs-6257579/v1/5eb8a8141cbad50eee968e76.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Lung Ultrasound Scoring-Driven Precision: A Non-Invasive Paradigm for Optimal Surfactant Timing in Neonatal Meconium Aspiration Syndrome","fulltext":[{"header":"What is Known – What is New","content":"\u003cp\u003eThis study addresses the limitations of traditional invasive metrics, which are associated with high complications and costs, by establishing the LUS score (\u0026ge;6) as a highly sensitive and specific indicator (AUC=0.9886) for precise PS initiation. Results show that LUS enables dynamic monitoring, optimizing PS use, reducing complications, and shortening hospital stays, with predictive accuracy surpassing traditional parameters. Its non-invasive, cost-effective nature promotes standardized clinical care, offering an innovative approach to personalized treatment and resource optimization.\u003c/p\u003e"},{"header":"1. INTRODUCTION","content":"\u003cp\u003eMeconium aspiration syndrome(MAS) is one of the common diseases of newborns. It is also a clinical disease characterized by respiratory attenuation that is more serious in near-term or full-term infants and post-term infants. Its accompanying complications are also a major challenge for clinicians\u003csup\u003e1\u003c/sup\u003e. Early diagnosis and early treatment are particularly critical. The use of pulmonary surfactant (PS) in MAS is a routine means of treating severe cases\u003csup\u003e2,3\u003c/sup\u003e, but there is still controversy and inconsistent standards on when to use PS. The Canadian Pediatric Society recommends\u003csup\u003e4\u003c/sup\u003e that PS should be used for all children with endotracheal intubation and oxygen concentration greater than 50%. China uses it for children with an oxygenation index(OI) greater than 8\u003csup\u003e5\u003c/sup\u003e. Natural PS is expensive, and its use should be rational.\u003c/p\u003e \u003cp\u003eIn MAS, a reliable predictive indicator is needed to evaluate the use of PS in MAS, which can not only help clinicians advance the window period for using PS, reduce the occurrence of complications, and shorten the overall hospitalization time, but also avoid abusing PS and causing an increase in overall hospitalization costs.Lung ultrasound is an emerging imaging technology in recent years\u003csup\u003e6\u0026ndash;8\u003c/sup\u003e. It has high specificity and sensitivity for the diagnosis of various lung diseases\u003csup\u003e9,10\u003c/sup\u003e, including MAS, and is increasingly favored by clinicians for its radiation-free and convenient bedside\u003csup\u003e11\u003c/sup\u003e. The predictive role of lung ultrasound in Neonatal respiratory distress syndrome has been confirmed\u003csup\u003e12\u0026ndash;21\u003c/sup\u003e. Lung ultrasound scores have a predictive effect on the timing of PS use in MAS with high sensitivity. This study aimed to explore the predictive value of Lung ultrasound (LUS) scores for the timing of PS use in children with MAS.\u003c/p\u003e \u003cp\u003eEarly intervention plays a crucial role in mitigating long-term developmental impairments in neonates with severe respiratory conditions, such as MAS. Delayed or inappropriate treatment may lead to persistent pulmonary hypertension (PPHN), prolonged mechanical ventilation, and an increased risk of neurodevelopmental delays.\u003c/p\u003e"},{"header":"2. MATERIALS AND METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1Ethical considerations and data privacy\u003c/h2\u003e \u003cp\u003eThis study was a prospective observational study conducted in two academic, tertiary centers for the treatment of severe neonates. Ethical approval was obtained from the ethics committees and review bodies of both centers. All parents of the newborns gave informed consent and signed the informed consent form. All authors supported the study protocol and decided to co-publish.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2Study subjects\u003c/h2\u003e \u003cp\u003eThis study collected data from 512 full-term newborns (gestational age 37\u0026ndash;42 weeks) from 2 critical neonatal rescue centers between 2019 and 2024. And newborns with clear amniotic fluid III\u0026deg; contamination after rupture of membranes or during delivery, inclusion criteria: MAS infants with gestational age 37\u0026ndash;42 weeks, amniotic fluid III contamination and requiring NICU treatment (n\u0026thinsp;=\u0026thinsp;218) \u003csup\u003e22\u003c/sup\u003e. Exclusion criteria: those with good birth conditions and mother-baby rooming-in (n\u0026thinsp;=\u0026thinsp;294). Clinical details were recorded as part of the study, including detailed information such as gestational age, gender, hospitalization status, and the presence or absence of complications.\u003c/p\u003e \u003cp\u003eFor children admitted to the NICU for treatment, two clinicians who are proficient in bedside ultrasound and have obtained relevant qualifications performed lung ultrasound examinations within half an hour after admission to score the lung conditions. (Pulmonary ultrasound scoring method and details: The lungs are usually divided into 6 areas with the two nipples as the connecting line. Each area is scored with a score of 0\u0026ndash;3 points, for a total of 18 points. The higher the score, the more serious the condition. \u003csup\u003e23\u003c/sup\u003e) Both doctors were unaware of the study before the conclusions were announced.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3Lung ultrasound score\u003c/h2\u003e \u003cp\u003eThe ultrasound appearance of each area is usually divided into 4 levels.\u003c/p\u003e \u003cp\u003e0 points: normal ventilation, visible lung sliding with A lines or a small number of (less than 2 separate) B lines.\u003c/p\u003e \u003cp\u003e1 point: reduced lung ventilation, more than 3 B lines, and there are spaces between the B lines without fusion.\u003c/p\u003e \u003cp\u003e2 points: severely reduced lung ventilation, fused B lines, with or without small subpleural consolidation.\u003c/p\u003e \u003cp\u003e3 points: lung consolidation, a wide range of tissue changes.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4Interventions\u003c/h2\u003e \u003cp\u003eAt the same time, we recorded the X-ray grade rating, oxygen concentration, OI, and Ph value in the electronic file. The decision on whether to use PS\u003csup\u003e24,25\u003c/sup\u003e was based on the oxygen concentration threshold (\u0026gt;\u0026thinsp;50%) combined with the OI index. The lung ultrasound score did not guide the treatment of PS. All data were recorded and analyzed anonymously and used only for research purposes. The ROC curve was used to analyze the predictive efficacy of each indicator for the timing of PS use, and the threshold was determined by the maximum Youden index.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.5Statistical Design and Data Analysis Methodology\u003c/h2\u003e \u003cdiv id=\"Sec8\" class=\"Section3\"\u003e \u003ch2\u003e2.5.1Statistical design and sample size rationality\u003c/h2\u003e \u003cp\u003eThis study used G*Power 3.1 software to conduct a priori statistical power analysis (α\u0026thinsp;=\u0026thinsp;0.05, Power\u0026thinsp;=\u0026thinsp;0.8). Based on preliminary experimental data, assuming that the difference in the area under the receiver operating characteristic curve (AUC) of lung ultrasound (LUS) scores and traditional OI is 0.1, the minimum sample size was calculated to be 200 cases. Finally, 218 children with meconium aspiration syndrome (MAS) were included, meeting the statistical power requirements.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section3\"\u003e \u003ch2\u003e2.5.2Lung ultrasound scoring and operator consistency\u003c/h2\u003e \u003cp\u003eLung ultrasound examinations were performed by two independent neonatologists (qualified to perform neonatal LUS) using a blind evaluation method (the operators were unaware of the clinical intervention plan and research hypothesis of the children). To verify inter-rater reliability, ultrasound images of 30 children were randomly selected for double-blind re-evaluation, and Fleiss' Kappa coefficient was used to evaluate classification consistency (κ\u0026thinsp;=\u0026thinsp;0.85, 95% CI: 0.76\u0026ndash;0.94), indicating that the scoring criteria were highly reproducible.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section3\"\u003e \u003ch2\u003e2.5.3Control of confounding variables and statistical modeling\u003c/h2\u003e \u003cp\u003eTo exclude the interference of potential confounding factors (gestational age, persistent pulmonary hypertension [PPHN], etc.) on the results, a multivariate logistic regression model was used for correction analysis. Pulmonary surfactant (PS) use was used as the dependent variable, LUS score was used as the core independent variable, gestational age (weeks), birth weight (g), and PPHN incidence were included as covariates, and the adjusted odds ratio (Adjusted OR) and 95% confidence interval were calculated. All statistical analyses were completed using SPSS 26.0, continuous variables were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation, and the Mann-Whitney U test was used for comparison between groups. Bilateral P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e2.6Data analysis\u003c/h2\u003e \u003cp\u003eROC curve showed that among the indicators of MAS using PS, the lung ultrasound score threshold was 5.5, the sensitivity was 99%, the specificity was 98%, the accuracy was 99%, and the area under the ROC curve (AUC) was 0.9886 (95% Cl: 0.9967-1, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The pH value threshold was 7.14, the sensitivity was 70%, the specificity was 91%, the accuracy was 83%, and the area under the ROC curve (AUC) was 0.9062 (95% Cl: 0.8676\u0026ndash;0.9448, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The oxygen concentration threshold was 47.5, the sensitivity was 85%, the specificity was 91%, the accuracy was 88%, and the area under the ROC curve (AUC) was 0.9527 (95% Cl: 0.9304\u0026ndash;0.9751, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The OI threshold was 7.5, the sensitivity was 91%, the specificity was 99%, the accuracy was 94%, and the area under the ROC curve (AUC) was 0.9673 (95% Cl: 0.9408\u0026ndash;0.9938, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The chest X-ray grade was excluded from the data analysis due to the inverted ROC curve, and there was no statistical significance (p\u0026thinsp;\u0026gt;\u0026thinsp;0.2).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e2.7Statistical analysis\u003c/h2\u003e \u003cp\u003eContinuous variables were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation and compared using the Mann-Whitney U test. Receiver operating curves were used to analyze the predictive value of lung ultrasound scores, pH, oxygen concentration, and OI for PS. Statistical analysis was performed using SPSS version 26.0 (IBM Corp, Armonk, New York, USA). A two-sided P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. RESULTS","content":"\u003cp\u003eDuring the study period, we included a total of 218 children with MAS. Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e provides the basic information of the experimental children and the research data of the children when PS was used. Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows that the maximum curve area was achieved when the lung ultrasound score was greater than 6 points (threshold 5.5), and the sensitivity and accuracy were significantly better than other indicators (Table\u0026nbsp;2), and the specificity was slightly lower than the OI (98%/100%). The hospitalization time of children in the LUS group was shorter than that in the traditional indicator group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), and the use rate of PPHN and ECMO was significantly reduced. Considering that the OI requires blood gas analysis and other invasive operations, ultrasound has the advantages of non-invasiveness, convenience, and repeatability. We still believe that ultrasound scoring is suitable for evaluating the timing of PS use in MAS.\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\u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo.Pts\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNon-Invasive Ventilation, (NIV)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo.Pts\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eInvasive Mechanical Ventilation(IMV)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP values\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGestational age\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e138\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e39.84\u0026thinsp;\u0026plusmn;\u0026thinsp;1.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e39.95\u0026thinsp;\u0026plusmn;\u0026thinsp;1.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.574\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLung ultrasound score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e138\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e4.02\u0026thinsp;\u0026plusmn;\u0026thinsp;0.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e8.79\u0026thinsp;\u0026plusmn;\u0026thinsp;2.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGrade of chest film\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e138\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e2.43\u0026thinsp;\u0026plusmn;\u0026thinsp;0.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e2.51\u0026thinsp;\u0026plusmn;\u0026thinsp;0.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.272\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFraction of inspiration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e138\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e34.11\u0026thinsp;\u0026plusmn;\u0026thinsp;8.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e52.94\u0026thinsp;\u0026plusmn;\u0026thinsp;6.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e138\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e7.21\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e7.07\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOxygenation Index\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e6.59\u0026thinsp;\u0026plusmn;\u0026thinsp;0.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e10.17\u0026thinsp;\u0026plusmn;\u0026thinsp;1.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospital stay\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e138\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e6.31\u0026thinsp;\u0026plusmn;\u0026thinsp;1.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e8.15\u0026thinsp;\u0026plusmn;\u0026thinsp;1.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.013\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e \u003ccolgroup cols=\"11\"\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 \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"10\" nameend=\"c10\" namest=\"c1\"\u003e \u003cp\u003eTable\u0026nbsp;2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"1\" nameend=\"c11\" namest=\"c11\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eVariables\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eThreshold\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e\u003cb\u003eSpecificity\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e\u003cb\u003eSencitivity\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e \u003cp\u003e\u003cb\u003eAccuracy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c11\" namest=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eLung ultrasound score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e0.986\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e0.999\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e \u003cp\u003e0.991\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c11\" namest=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eFraction of inspiration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e47.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e0.913\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e0.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e \u003cp\u003e0.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c11\" namest=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003epH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e0.913\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e \u003cp\u003e0.835\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c11\" namest=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eOxygenation Index\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e0.999\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e0.913\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e \u003cp\u003e0.949\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c11\" namest=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"4. DISCUSSION","content":"\u003cp\u003eWe have proved that lung ultrasound scoring does have a guiding role in MAS\u003csup\u003e26,27\u003c/sup\u003e. On the one hand, lung ultrasound scoring can be used to determine the lung condition, thereby guiding clinicians to use PS as early as possible to avoid serious complications such as persistent pulmonary hypertension (PPHN) and extracorporeal membrane oxygenation (ECMO). On the other hand, since natural PS is expensive, lung ultrasound scoring can also avoid the economic pressure caused by excessive medical treatment. LUS can be used to accurately determine the timing of PS use and has shown obvious advantages.\u003c/p\u003e \u003cp\u003eFirst of all, we need to understand that the purpose of using PS is to reduce the occurrence of complications\u003csup\u003e28,29\u003c/sup\u003e, reduce hospitalization time and reverse lung conditions as soon as possible. From the existing data, even the combined diagnosis (oxygen concentration combined with oxygenation index) is still less sensitive than lung ultrasound. Secondly, all other indicators currently known need to be performed under invasive operations. For children with severe MAS and PPHN, it is undoubtedly a major blow. The advantages of ultrasound are self-evident.\u003c/p\u003e \u003cp\u003eSecondly, MAS in full-term infants is a pathophysiological feature formed by multiple factors. Multiple factors can inactivate PS\u003csup\u003e30\u003c/sup\u003e, including chemical and physical inflammatory stimuli; meconium blocks the airway, and partial blockage can produce a valve-like effect, leading to uneven lung expansion; meconium fatty acids can directly act on alveolar type II cells to produce toxic effects, changing the viscosity and ultrastructure of pulmonary surfactant, etc.\u003csup\u003e31\u003c/sup\u003e. Since meconium inhalation is not uniform, treatment mostly adopts a general and broad model. LUS can evaluate which area has more severe lesions and guide treatment more accurately and targetedly.\u003c/p\u003e \u003cp\u003eThirdly, LUS can dynamically track the condition of lung lesions after using PS\u003csup\u003e32\u003c/sup\u003e, predicting or advancing the treatment time window for severe complications. LUS determines the condition of the lungs through ultrasound artifacts, and can determine the change of the condition through lung ultrasound scores and direct lung ventilation imaging, and evaluate whether PS needs to be used again and guide weaning.\u003c/p\u003e \u003cp\u003eFourth, early changes in lung compliance and the promotion of meconium excretion are the key to treating MAS. Ventilation strategies and the use of ECMO can be achieved through LUS. In the treatment of MAS, LUS has great advantages\u003csup\u003e33\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe advantages of LUS in clinical practice are well known. Its advantages such as no radiation, rapidity, and convenience are suitable for NICU, especially for critically ill newborns34. The purpose of our study is to use LUS to standardize the treatment of MAS and standardize the use of PS and ventilation strategies according to the severity of the child's condition. Since the remaining indicators included in the study almost require invasive operations, this seems to be unfriendly to children with MAS who may have PPHN, and the accuracy and sensitivity are inferior to LUS.\u003c/p\u003e \u003cp\u003eNeonatal diseases develop rapidly. Most of the late complications of improper early MAS treatment are very difficult. The key to treatment is for clinicians to quickly identify and grasp the characteristics of the disease. LUS can help clinicians better identify the disease and guide the treatment plan\u003csup\u003e35,36\u003c/sup\u003e, which is different from the \"organic\" examination preferred by ultrasound doctors\u003csup\u003e37\u003c/sup\u003e. Under the guidance of LUS, the hospitalization time of children is significantly shortened compared with traditional treatment. Medical resources are saved.\u003c/p\u003e \u003cp\u003eLUS is accurate and reliable in determining MAS. The typical ultrasound evidence of MAS can be used for reference: 1. Pulmonary consolidation with bronchial inflation (irregular or jagged shadows of varying sizes at the boundary of the consolidation area). 2. Abnormal pleural line (thickening, rupture or blur). 3. B-lines or alveolar-interstitial syndrome (AIS) can be seen in non-consolidation areas. 4. Pleural effusion. 5. Atelectasis\u003csup\u003e38\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eFinally, the choice of probe is preferred. Linear probe is preferred. Since most MAS are near-term or full-term infants or overdue infants, high-frequency probes are not penetrating enough, and the frequency can be reduced or replaced with a linear array probe with a slightly lower frequency. However, since a considerable number of diseases treated in NICU are premature infants, the probe frequency can now be selected from 9-14MHz to adapt to more diseases.\u003c/p\u003e"},{"header":"5. CONCLUSION","content":"\u003cp\u003eLUS score\u0026thinsp;\u0026ge;\u0026thinsp;6 is a reliable indicator for initiating PS treatment in children with MAS, which can advance the treatment window, reduce complications and shorten hospitalization time. It is recommended to incorporate LUS into the standardized diagnosis and treatment process of MAS to improve clinical decision-making efficiency.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eAll authors declare no conflicts of interest and agree to the publication of this study. For access to the raw data, please contact the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDetails of Ethical Approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study has been approved by the Ethics Committee of Shangrao Maternal and Child Health Hospital, with the ethical approval number \u003cstrong\u003eSRFB20231206037\u003c/strong\u003e, dated December 6, 2023. The contact address of the Ethics Committee is Shangrao Maternal and Child Health Hospital, No. 55 Shangrao Avenue, Xinzhou District, Shangrao City, Jiangxi Province, China. The contact telephone number is\u003cstrong\u003e\u0026nbsp;0793-8209562\u003c/strong\u003e\u003cstrong\u003e(\u003c/strong\u003e\u003cstrong\u003ePlease refer to the supplementary materials for the original ethics review document, which has been uploaded.\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study strictly adheres to the Declaration of Helsinki and relevant ethical guidelines, ensuring the full protection of participants\u0026apos; rights to informed consent, privacy, and data security. All participants signed informed consent forms upon admission, clearly understanding the purpose, procedures, potential risks, and benefits of the study. No unnecessary risks or harm were imposed on participants during the research process.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eQi Chen: Conceptualization; Investigation; Software; Formal analysis; Writing - review \u0026amp; editing. Lei Cao: Conceptualization; Methodology; Investigation. Wei Xiong: Conceptualization; Investigation; Writing - original draft; Writing - review \u0026amp; editing; Methodology; Validation; Software; Formal analysis. Zekai Yu:Conceptualization; Investigation; Formal analysis; Methodology. MaoHua Wu: Conceptualization; Investigation; Software.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eShaikh, M, Irfan Waheed, KA, Javaid, S, Gul, R, Hashmi, MA, Fatima, ST. Detrimental Complications Of Meconium Aspiration Syndrome And Their Impact On Outcome. J Ayub Med Coll Abbottabad. 2016-01-01; 28 (3): 506-509. PMID: 28712223.\u003c/li\u003e\n\u003cli\u003eStevens, TP, Harrington, EW, Blennow, M, Soll, RF. Early surfactant administration with brief ventilation vs. selective surfactant and continued mechanical ventilation for preterm infants with or at risk for respiratory distress syndrome. Cochrane Database Syst Rev. 2007-10-17; (4): CD003063. doi: 10.1002/14651858.CD003063.pub3. PMID: 17943779.\u003c/li\u003e\n\u003cli\u003eSweet, DG, Carnielli, V, Greisen, G, Hallman, M, Ozek, E, Te Pas, A, Plavka, R, Roehr, CC, Saugstad, OD, Simeoni, U, Speer, CP, Vento, M, Visser, GHA, Halliday, HL. European Consensus Guidelines on the Management of Respiratory Distress Syndrome - 2019 Update. NEONATOLOGY. 2019-01-01; 115 (4): 432-450. doi: 10.1159/000499361. PMID: 30974433.\u003c/li\u003e\n\u003cli\u003eRecommendations for neonatal surfactant therapy. PAED CHILD HEALT-CAN. 2005-02-01; 10 (2): 109-16. PMID: 19668609.\u003c/li\u003e\n\u003cli\u003eWillson, DF, Jiao, JH, Bauman, LA, Zaritsky, A, Craft, H, Dockery, K, Conrad, D, Dalton, H. Calf\u0026apos;s lung surfactant extract in acute hypoxemic respiratory failure in children. CRIT CARE MED. 1996-08-01; 24 (8): 1316-22. doi: 10.1097/00003246-199608000-00008. PMID: 8706485.\u003c/li\u003e\n\u003cli\u003eSingh, Y, Dauengauer-Kirliene, S, Yousef, N. Setting the Standards: Neonatal Lung Ultrasound in Clinical Practice. Diagnostics (Basel). 2024-07-02; 14 (13): doi: 10.3390/diagnostics14131413. PMID: 39001302;.\u003c/li\u003e\n\u003cli\u003eYousef, N, Piastra, M, Brat, R, Manzoni, P, Mokhtari, M, Tissieres, P, De Luca, D. PO-0774 Lung Ultrasound Findings In Meconium Aspiration Syndrome ARCH DIS CHILD. 2014-10-01; 99 (Suppl 2): A508.3-A509. doi: 10.1136/archdischild-2014-307384.1413.\u003c/li\u003e\n\u003cli\u003eWu, J, Su, C, Mao, Y. The value of lung ultrasound in the differential diagnosis of common lung diseases in newborns. MEDICINE. 2024-11-08; 103 (45): e40459. doi: 10.1097/MD.0000000000040459. PMID: 39533624.\u003c/li\u003e\n\u003cli\u003eYousef, N. [Lung ultrasound in the newborn]. ARCH PEDIATRIE. 2016-03-01; 23 (3): 317-21. doi: 10.1016/j.arcped.2015.12.001. PMID: 26879968.\u003c/li\u003e\n\u003cli\u003eGuideline on lung ultrasound to diagnose pulmonary diseases in newborn infants]. Zhongguo Dang Dai Er Ke Za Zhi. 2019-02-01; 21 (2): 105-113. PMID: 30782270.\u003c/li\u003e\n\u003cli\u003eLichtenstein, DA, Mauriat, P. Lung Ultrasound in the Critically Ill Neonate. CURR PEDIATR REV. 2012-08-01; 8 (3): 217-223. doi: 10.2174/157339612802139389. PMID: 23255876.\u003c/li\u003e\n\u003cli\u003eDe Martino L, Yousef N, Ben-Ammar R, Raimondi F, Shankar-Aguilera S, De Luca D. Lung Ultrasound Score Predicts Surfactant Need in Extremely Preterm Neonates. Pediatrics. 2018 Sep;142(3):e20180463 . doi: 10.1542/peds.2018-0463. PMID: 30108142.\u003c/li\u003e\n\u003cli\u003eBao, LY, Dao, XY, Du, K. Progress in the Application of Lung Ultrasound for the Evaluation of Neonates with Respiratory Distress Syndrome. J Multidiscip Healthc. 2024-01-01; 17 1-9. doi: 10.2147/JMDH.S442464. PMID: 38192739.\u003c/li\u003e\n\u003cli\u003eSingh, Y, Tissot, C, Fraga, MV, Yousef, N, Cortes, RG, Lopez, J, Sanchez-de-Toledo, J, Brierley, J, Colunga, JM, Raffaj, D, Da Cruz, E, Durand, P, Kenderessy, P, Lang, HJ, Nishisaki, A, Kneyber, MC, Tissieres, P, Conlon, TW, De Luca, D. International evidence-based guidelines on Point of Care Ultrasound (POCUS) for critically ill neonates and children issued by the POCUS Working Group of the European Society of Paediatric and Neonatal Intensive Care (ESPNIC). CRIT CARE. 2020-02-24; 24 (1): 65. doi: 10.1186/s13054-020-2787-9. PMID: 32093763.\u003c/li\u003e\n\u003cli\u003eCorsini, I, Parri, N, Gozzini, E, Coviello, C, Leonardi, V, Poggi, C, Giacalone, M, Bianconi, T, Tofani, L, Raimondi, F, Dani, C. Lung Ultrasound for the Differential Diagnosis of Respiratory Distress in Neonates. NEONATOLOGY. 2019-01-01; 115 (1): 77-84. doi: 10.1159/000493001. PMID: 30304736.\u003c/li\u003e\n\u003cli\u003eDong, J, Deng, Y, Tong, J, Du, T, Liu, W, Guo, Y. The diagnostic value and efficacy evaluation of lung ultrasound score in neonatal respiratory distress syndrome: a prospective observational study. Front Pediatr. 2025-01-01; 13 1500500. doi: 10.3389/fped.2025.1500500. PMID: 39950156.\u003c/li\u003e\n\u003cli\u003eSzymański, P, Kruczek, P, Hożejowski, R, Wais, P. Modified lung ultrasound score predicts ventilation requirements in neonatal respiratory distress syndrome. BMC Pediatr. 2021-01-06; 21 (1): 17. doi: 10.1186/s12887-020-02485-z. PMID: 33407270.\u003c/li\u003e\n\u003cli\u003eChan, B, Torsitano, C, Gordon, S, Konana, O, Singh, Y. Substantiating and Adopting Lung Ultrasound Scores to Predict Surfactant Need in Preterm Neonates with Respiratory Distress Syndrome within an Institution. AM J PERINAT. 2024-09-01; 41 (12): 1652-1659. doi: 10.1055/s-0044-1779500. PMID: 38346693;\u003c/li\u003e\n\u003cli\u003eGupta, D, Priyadarshi, M, Chaurasia, S, Singh, P, Basu, S. Lung ultrasound for prediction of surfactant requirement in Indian preterm neonates: a diagnostic accuracy study. EUR J PEDIATR. 2024-08-01; 183 (8): 3599-3606. doi: 10.1007/s00431-024-05626-z. PMID: 38829378.\u003c/li\u003e\n\u003cli\u003eAldecoa-Bilbao, V, Balcells-Esponera, C, Herranz Barbero, A, Borr\u0026agrave;s-Novell, C, Izquierdo Renau, M, Iriondo Sanz, M, Salvia Roig\u0026eacute;s, M. Lung ultrasound for early surfactant treatment: Development and validation of a predictive model. PEDIATR PULM. 2021-02-01; 56 (2): 433-441. doi: 10.1002/ppul.25216. PMID: 33369257.\u003c/li\u003e\n\u003cli\u003eRaimondi, F, Migliaro, F, Corsini, I, Meneghin, F, Dolce, P, Pierri, L, Perri, A, Aversa, S, Nobile, S, Lama, S, Varano, S, Savoia, M, Gatto, S, Leonardi, V, Capasso, L, Carnielli, VP, Mosca, F, Dani, C, Vento, G, Lista, G. Lung Ultrasound Score Progress in Neonatal Respiratory Distress Syndrome. PEDIATRICS. 2021-04-01; 147 (4): doi: 10.1542/peds.2020-030528. PMID: 33688032.\u003c/li\u003e\n\u003cli\u003eSaint-Fleur, AL, Alcal\u0026aacute;, HE, Sridhar, S. Outcomes of neonates born through meconium-stained amniotic fluid pre and post 2015 NRP guideline implementation. PLoS One. 2023-01-01; 18 (8): e0289945. doi: 10.1371/journal.pone.0289945. PMID: 37561740.\u003c/li\u003e\n\u003cli\u003eKelner, J, Moote, D, Shah, R, Anuar, A, Golioto, A. Lung Ultrasound Score for Prediction of Surfactant Administration in Preterm Infants with Respiratory Failure. J PERINATOL. 2024-09-01; 44 (9): 1258-1263. doi: 10.1038/s41372-024-02090-3. PMID: 39122885. \u003c/li\u003e\n\u003cli\u003eBrat, R, Yousef, N, Klifa, R, Reynaud, S, Shankar Aguilera, S, De Luca, D. Lung Ultrasonography Score to Evaluate Oxygenation and Surfactant Need in Neonates Treated With Continuous Positive Airway Pressure. JAMA PEDIATR. 2015-08-01; 169 (8): e151797. doi: 10.1001/jamapediatrics.2015.1797. PMID: 26237465.\u003c/li\u003e\n\u003cli\u003eEl Shahed, AI, Dargaville, PA, Ohlsson, A, Soll, R. Surfactant for meconium aspiration syndrome in term and late preterm infants. Cochrane Database Syst Rev. 2014-12-14; (12): CD002054. doi: 10.1002/14651858.CD002054.pub3. PMID: 25504256.\u003c/li\u003e\n\u003cli\u003ePiastra, M, Yousef, N, Brat, R, Manzoni, P, Mokhtari, M, De Luca, D. Lung ultrasound findings in meconium aspiration syndrome. EARLY HUM DEV. 2014-09-01; 90 Suppl 2 S41-3. doi: 10.1016/S0378-3782(14)50011-4. PMID: 25220126.\u003c/li\u003e\n\u003cli\u003eYeh, TF, Harris, V, Srinivasan, G, et al. Roentgenographic findings in infants with meconium aspiration syndrome. JAMA-J AM MED ASSOC. 1979; 242 (1): 60-3. PMID: 448867.\u003c/li\u003e\n\u003cli\u003eDargaville, PA, Mills, JF. Surfactant therapy for meconium aspiration syndrome: current status. DRUGS. 2005-01-01; 65 (18): 2569-91. doi: 10.2165/00003495-200565180-00003. PMID: 16392874.\u003c/li\u003e\n\u003cli\u003eJobe, AH. Commentary on surfactant treatment of neonates with respiratory failure and group B streptococcal infection PEDIATRICS. 2000-11-01; 106 (5): 1135. doi: 10.1542/peds.106.5.1135. PMID: 11061786.\u003c/li\u003e\n\u003cli\u003eVain, NE, Batton, DG. Meconium \u0026quot;aspiration\u0026quot; (or respiratory distress associated with meconium-stained amniotic fluid?). SEMIN FETAL NEONAT M. 2017-08-01; 22 (4): 214-219. doi: 10.1016/j.siny.2017.04.002. PMID: 28411000.\u003c/li\u003e\n\u003cli\u003eSchrama, AJ, de Beaufort, AJ, Sukul, YR, Jansen, SM, Poorthuis, BJ, Berger, HM. Phospholipase A2 is present in meconium and inhibits the activity of pulmonary surfactant: an in vitro study. ACTA PAEDIATR. 2001-04-01; 90 (4): 412-6. PMID: 11332933.\u003c/li\u003e\n\u003cli\u003eArayici, S, Sari, FN, Kadioglu Simsek, G, Yarci, E, Alyamac Dizdar, E, Uras, N, Canpolat, FE, Oguz, SS. Lung Lavage with Dilute Surfactant vs. Bolus Surfactant for Meconium Aspiration Syndrome. J TROP PEDIATRICS. 2019-10-01; 65 (5): 491-497. doi: 10.1093/tropej/fmy081. PMID: 30690595.\u003c/li\u003e\n\u003cli\u003eBendapudi, P, Rao, GG, Greenough, A. Diagnosis and management of persistent pulmonary hypertension of the newborn. PAEDIATR RESPIR REV. 2015-06-01; 16 (3): 157-61. doi: 10.1016/j.prrv.2015.02.001. PMID: 25765845.\u003c/li\u003e\n\u003cli\u003eVolpicelli, G, Elbarbary, M, Blaivas, M, Lichtenstein, DA, Mathis, G, Kirkpatrick, AW, Melniker, L, Gargani, L, Noble, VE, Via, G, Dean, A, Tsung, JW, Soldati, G, Copetti, R, Bouhemad, B, Reissig, A, Agricola, E, Rouby, JJ, Arbelot, C, Liteplo, A, Sargsyan, A, Silva, F, Hoppmann, R, Breitkreutz, R, Seibel, A, Neri, L, Storti, E, Petrovic, T. International evidence-based recommendations for point-of-care lung ultrasound. INTENS CARE MED. 2012-04-01; 38 (4): 577-91. doi: 10.1007/s00134-012-2513-4. PMID: 22392031.\u003c/li\u003e\n\u003cli\u003eCorsini, I, Parri, N, Ficial, B, Dani, C. Lung ultrasound in the neonatal intensive care unit: Review of the literature and future perspectives. PEDIATR PULM. 2020-07-01; 55 (7): 1550-1562. doi: 10.1002/ppul.24792. PMID: 32339409.\u003c/li\u003e\n\u003cli\u003eFirszt, O, Grabowska, A, Saran, A, Kluczewska, E. Implementation of a standardized lung ultrasound protocol for respiratory distress in a neonatal intensive care unit: an observational study. J PERINATOL. 2024-09-01; 44 (9): 1264-1268. doi: 10.1038/s41372-024-01900-y. PMID: 38361003.\u003c/li\u003e\n\u003cli\u003eRaimondi, 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. 2021-09-01; 90 (3): 524-531. doi: 10.1038/s41390-018-0114-9. PMID: 30127522.\u003c/li\u003e\n\u003cli\u003eBouhemad, B, Zhang, M, Lu, Q, Rouby, JJ. Clinical review: Bedside lung ultrasound in critical care practice. CRIT CARE. 2007-01-01; 11 (1): 205. doi: 10.1186/cc5668. PMID: 17316468;\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"
[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Neonatal meconium aspiration syndrome, lung ultrasound, pulmonary surfactant, neonatal intensive care unit, lung ultrasound score","lastPublishedDoi":"10.21203/rs.3.rs-6257579/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6257579/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground\u003c/b\u003e\u003c/p\u003e \u003cp\u003eMeconium aspiration syndrome (MAS) is a severe respiratory disease in neonates, and the timing of the application of pulmonary surfactant (PS) is still controversial. Lung ultrasound (LUS), as a non-invasive, highly sensitive and specific imaging technique, may provide a basis for the precise use of PS.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThis study was a prospective observational study, and 218 MAS infants from two tertiary neonatal rescue centers were included. The LUS score (total score of 18 points, divided into 6 zones) was compared with traditional indicators (oxygenation index, oxygen concentration, etc.), and the ROC curve was used to analyze the predictive efficiency.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003eWhen the LUS score threshold was 5.5 points (actually 6 points), the AUC for predicting the timing of PS use was 0.9886 (95% CI: 0.9967-1), with a sensitivity of 99% and a specificity of 98%, which was significantly better than the oxygenation index (AUC\u0026thinsp;=\u0026thinsp;0.9673), oxygen concentration (AUC\u0026thinsp;=\u0026thinsp;0.9527) and pH value (AUC\u0026thinsp;=\u0026thinsp;0.9062). LUS is non-invasive and repeatable, and can reduce complications (such as PPHN) and hospital stay.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusion\u003c/b\u003e\u003c/p\u003e \u003cp\u003eLUS score\u0026thinsp;\u0026ge;\u0026thinsp;6 is a reliable indicator for initiating PS treatment in children with MAS, which can optimize the timing of treatment and improve clinical prognosis.\u003c/p\u003e","manuscriptTitle":"Lung Ultrasound Scoring-Driven Precision: A Non-Invasive Paradigm for Optimal Surfactant Timing in Neonatal Meconium Aspiration Syndrome","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-21 08:43:18","doi":"10.21203/rs.3.rs-6257579/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"
[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e51c88cf-5387-4e31-9c6c-3655edec10c7","owner":[],"postedDate":"April 21st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-06-11T11:08:57+00:00","versionOfRecord":[],"versionCreatedAt":"2025-04-21 08:43:18","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6257579","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6257579","identity":"rs-6257579","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}
Text is read by the "Ask this paper" AI Q&A widget below.
Extraction quality varies by source — PMC NXML preserves structure
cleanly, OA-HTML may include some navigation residue, and OA-PDF can
have broken hyphenation. The publisher copy
(via DOI)
is the canonical version.