Optimal timing and cutoff range of lung ultrasound in predicting surfactant administration in neonates: A meta-analysis and systematic review

PLOS ONE RESEARCH ARTICLE Optimal timing and cutoff range of lung ultrasound in predicting surfactant administration in neonates: A meta-analysis and systematic review Keren Luo1, Haoran Wang2, Fangjun Huang2, Jun Tang ID1* a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 1 Department of Neonatology, West China Second Hospital, Sichuan University/Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu City, Sichuan Province, China, 2 West China School of Medicine, Sichuan University, Chengdu City, Sichuan Province, China * Abstract OPEN ACCESS Citation: Luo K, Wang H, Huang F, Tang J (2023) Optimal timing and cutoff range of lung ultrasound in predicting surfactant administration in neonates: A meta-analysis and systematic review. PLoS ONE 18(7): e0287758. https://doi.org/10.1371/journal. pone.0287758 Editor: Atnafu Mekonnen Tekleab, St Paul’s Hospital Millennium Medical College, ETHIOPIA Received: April 23, 2023 Objective Timely application of surfactant replacement therapy is critical for neonates with respiratory distress syndrome (RDS). Presently, early clinical decision on surfactant use relies solely on ventilator parameters. However, ventilator parameters are unable to truly recapitulate the extent of surfactant deficiency. Lung ultrasound has been increasingly used in the early prediction of surfactant use in recent years, but its predictive value remains unclear. Therefore, we conducted this study to examine its predictive value in surfactant use and determine the optimal timing and cutoff value. Accepted: June 11, 2023 Published: July 27, 2023 Methods Copyright: © 2023 Luo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Studies on neonates with respiratory distress or diagnosed with RDS were collected from PubMed, Embase, Cochrane Library, and Web of Science. Primary outcomes included sensitivity, specificity, and positive and negative predictive values of lung ultrasound. Data Availability Statement: All relevant data are within the paper and its Supporting information files. Funding: This work was supported by National Natural Science Foundation of China (General Project, 82171710). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: The authors have declared that no competing interests exist. Results Ten eligible studies with 1162 participants were included. The sensitivity and specificity of lung ultrasound in predicting surfactant use were 0.86 (95% CI: 0.81–0.90) and 0.82 (95% CI: 0.71–0.90), respectively. Lung ultrasound performed within 1–3 h after birth had a sensitivity of 0.89 (95% CI: 0.79–0.95) and a Youden’s index of 0.67. Compared with a lung ultrasound score (LUS) cutoff of �6/7, �8, >5, >6/7, and >8, a LUS cutoff of �5 had higher Youden’s index (0.73) and sensitivity (0.94, 95% CI: 0.85–0.97) in predicting surfactant use. PLOS ONE | https://doi.org/10.1371/journal.pone.0287758 July 27, 2023 1 / 12 PLOS ONE Lung ultrasound predict surfactant use Conclusions Lung ultrasound is effective for predicting surfactant use in neonates. Lung ultrasound within 1–3 h after birth and a LUS cutoff of 5 are recommended. However, the symptoms and oxygenation of the neonatal patients must also be considered. Introduction Surfactant replacement therapy has been shown to effectively improve early respiratory distress and late prognosis of respiratory distress syndrome (RDS) neonates within 3 h of birth [1]. Current clinical practices emphasize the early use of surfactant to improve prognosis of neonates exhibiting symptoms of respiratory distress, such as shortness of breath, grunting, dyspnea, and transcutaneous oxygen saturation of <0.90 in the absence of oxygen inhalation [2]. However, not all neonates require surfactant since those with transient tachypnea of the newborn (TTN) may exhibit these symptoms. Therefore, clinical guidelines [3] and expert consensus [4] have added the use of ventilator parameters when determining surfactant use. The 2019 European Consensus Guidelines recommended FiO2 > 0.30 as the dosing cutoff for all neonates with clinically diagnosed RDS [3]. In addition, the 2021 Chinese Expert Consensus specified that a CPAP �6 cmH2O is an indication for surfactant use [4]. However, ventilator parameters are unable to truly recapitulate the extent of surfactant deficiency and are largely influenced by the type of respiratory support and degree of oxygenation. Thus, there are limitations in solely relying on clinical symptoms and ventilator parameters when determining surfactant use, which can result in unnecessary surfactant use or missing the best timing of surfactant. Due to its timeliness, convenience, and radiation-free advantages, lung ultrasound has gained wide application in the neonatal ward in recent years. Two meta-analyses in 2020 pointed out that lung ultrasound has relatively high sensitivity and specificity for diagnosing neonatal RDS and may replace chest X-ray as the diagnostic measure [5, 6]. In addition, lung ultrasound has also demonstrated relatively high accuracy in diagnosing neonatal TTN [7]. Furthermore, Liu et al. [8] established standards and guidelines for the instrument operation and parameter setting of lung ultrasound in neonates, which further improved the accuracy and reliability of the procedure. Though, it is worth noting that qualitative evaluation by lung ultrasound is somewhat subjective, which renders the procedure difficult for wide clinical application. Moreover, only using lung ultrasound as a means of disease diagnosis cannot maximize its role in assessing pulmonary oxygenation in neonates. Consequently, Brat et al. [9] designed a scoring system that allows semi-quantitation by lung ultrasound. Furthermore, other studies have used the distribution of A-lines and B-lines to classify lung ultrasound images into different types [10, 11]. It has been reported that lung ultrasound score (LUS) can effectively identify failure of noninvasive assisted ventilation in neonatal RDS patients [11–14]. This then raises the question of whether LUS can predict surfactant use in RDS patients. Although many studies have confirmed the significance of LUS in guiding surfactant use [9, 15–26], the LUS cutoff value was inconsistently selected based on gestational age [9] or different timing of lung ultrasound [22]. Here, we performed a meta-analysis of the predictive value of lung ultrasound in surfactant use and assessed the optimal LUS cutoff value and timing of lung ultrasound to standardize the clinical application of surfactant and to rationalize and refine the treatment of neonatal diseases. Methods This systematic review and meta (...truncated)