Can lung ultrasound score accurately predict the need for surfactant replacement in preterm neonates? A systematic review and meta-analysis protocol

PLOS ONE STUDY PROTOCOL Can lung ultrasound score accurately predict the need for surfactant replacement in preterm neonates? A systematic review and meta-analysis protocol Letizia Capasso ID1*, Daniela Pacella2, Fiorella Migliaro1, Daniele De Luca3, Francesco Raimondi1 a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 1 Division of Neonatology, Department of Translational Medical Sciences, University Federico II, Naples, Italy, 2 Department of Public Health, University Federico II, Naples, Italy, 3 Service de Pediatrie et Reanimation Neonatale Hopital “A. Beclere” – GHU Paris Saclay, APHP, Paris, France * Abstract OPEN ACCESS Citation: Capasso L, Pacella D, Migliaro F, De Luca D, Raimondi F (2021) Can lung ultrasound score accurately predict the need for surfactant replacement in preterm neonates? A systematic review and meta-analysis protocol. PLoS ONE 16(7): e0255332. https://doi.org/10.1371/journal. pone.0255332 Editor: Kazumichi Fujioka, Kobe University Graduate School of Medicine School of Medicine, JAPAN Received: April 15, 2021 Respiratory distress syndrome (RDS) is a leading cause of morbidity and mortality in preterm infants due to primary surfactant deficiency. Surfactant replacement has greatly improved the short and long term prognosis of RDS but its administration criteria remain uncertain. Lung ultrasound has been recently shown as a non-invasive, repeatable, bedside tool to estimate parenchymal aeration using a semiquantitative score (LUS). The objective of this systematic review and meta-analysis is to evaluate the accuracy of LUS, assessed on the first day of life, to predict surfactant replacement. Methods will follow the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines and the protocol has been registered in PROSPERO database (registration number: CRD42021247888). Primary outcome: in a population of preterm infants, LUS will be compared in neonates who received surfactant replacement versus those who did not. Secondary outcome will be the accuracy of lung ultrasound score to predict the need for � 2 doses of surfactant. Published: July 28, 2021 Peer Review History: PLOS recognizes the benefits of transparency in the peer review process; therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. The editorial history of this article is available here: https://doi.org/10.1371/journal.pone.0255332 Copyright: © 2021 Capasso 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. Funding: The authors received no specific funding for this work. Introduction Respiratory distress syndrome (RDS) is a leading cause of morbidity and mortality in preterm infants due to primary surfactant deficiency. Surfactant replacement has greatly improved the short and long term prognosis of moderate to severe RDS, especially when administered in the first 3 hours of life [1]. Since not all preterm babies with RDS need surfactant, its administration criteria are still being debated. According to European guidelines, surfactant has to be administrated when oxygen requirement increases above 30% [2]. Rather than being a true index of surfactant deficiency, the oxygen requirement threshold is a proxy that also depends on the respiratory support delivered to the neonate (e.g. the PEEP level) and on the saturation target. These interdependencies may delay surfactant treatment or lead to unnecessary replacement. Lung ultrasound PLOS ONE | https://doi.org/10.1371/journal.pone.0255332 July 28, 2021 1/5 PLOS ONE Competing interests: The authors have declared that no competing interests exist. Can lung ultrasound score accurately predict the need for surfactant replacement in preterm neonates? has been recently shown as a non-invasive, repeatable, bedside tool to estimate parenchymal aeration using a semiquantitative score [3,4]. Several groups have shown that a lung ultrasound score (LUS) is a reliable marker to predict the failure of non-invasive support in infants with RDS [5–8]. As a natural consequence, clinicians are investigating LUS thresholds for surfactant replacement as an alternative to or in association with oxygenation markers [3]. Since results may also depend on study populations, score threshold and scoring system, the need for recapitulation and standardization arises. The goal is to establish the role of LUS as a clinically relevant tool for surfactant administration as already hypothesized in the 2019 European guidelines on RDS [2]. Objective This systematic review and meta-analysis concerns the accuracy of LUS, assessed on the first day of life, to predict surfactant replacement in preterm neonates. Methods We will follow the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines [9] and the protocol has been registered in PROSPERO database (registration number: CRD42021247888). The PRISMA-P 2015 Checklist has been added as supporting information (S1 Checklist). Eligibility criteria The PICOS elements form the basis of clinical questions for this review. Studies will be selected according to the criteria outlined below. Participants Inclusion criteria: all preterm neonates having LUS assessed on the first day of life. Exclusion criteria: neonates with congenital malformations, TORCH infections. Interventions 1. lung ultrasound score assessed in preterm neonates on the first day of life before surfactant treatment 2. lung ultrasound scan performed on at least three areas for each lung. 3. we considered studies with the scoring systems including score = 0 for normal lung imaging (A lines and pleural sliding present); score = 1 for alveolar interstitial pattern (B lines not coalescent); score = 2 for severe alveolar interstitial pattern (multiple and or coalescent B lines with or without consolidations limited to subpleural space); score = 3 for extended consolidation [4,10]. Comparators Lung ultrasound score will be compared in preterm neonates who received surfactant treatment versus preterm infants who did not receive it. Other relevant clinical variables: gestational age (GA); Oxygen Saturation over Inspired Oxygen Fraction (S/F); small for gestational age (SGA); male gender and prenatal steroids administration. PLOS ONE | https://doi.org/10.1371/journal.pone.0255332 July 28, 2021 2/5 PLOS ONE Can lung ultrasound score accurately predict the need for surfactant replacement in preterm neonates? Outcomes Accuracy of lung ultrasound score, performed on the first day of life, to predict the subsequently need of surfactant treatment. Study design We will consider any kind of trial on the LUS accuracy to predict need of surfactant treatment in preterm neonates written in English betw (...truncated)