{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T14:45:13Z","timestamp":1789829113446,"version":"4.0.1"},"reference-count":60,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100020218","name":"Chiesi USA","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020218","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Pulmonology"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Less invasive surfactant administration (LISA) is increasingly used in preterm infants with respiratory distress syndrome (RDS). Understanding its safety profile compared to the INtubation\u2010SURfactant\u2010Extubation (INSURE) or endotracheal tube (ETT) techniques is essential.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate the safety profile of LISA compared to INSURE\/ETT in preterm infants with RDS using evidence from randomized and non\u2010randomized studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A systematic literature review identified studies in MEDLINE, EMBASE, and CENTRAL (2010\u20132024). Arm\u2010level pooled incidence estimates were generated across RCTs and non\u2010randomized studies, and pairwise comparisons of LISA versus INSURE\/ETT were conducted in randomized controlled trials (RCTs). Analyses utilized Generalized Linear Mixed Models with random\u2010effects. Subgroups included gestational age (\u2264\u200934 weeks), surfactant type, antenatal steroid exposure (\u2265\u200950%) and sedation and premedication use.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Nineteen RCTs (2460 infants) and 26 non\u2010randomized studies (2360 infants) met inclusion criteria. Pairwise comparisons revealed no statistically significant differences between LISA and INSURE\/ETT for apnea, bradycardia, cough, hypoxemia, or need for \u2265\u20092 attempts for successful catheter\/ETT placement attempts; however, surfactant regurgitation\/reflux occurred more frequently with LISA (OR\u2009=\u20092.29, 95% CI\u2009=\u20091.21\u20134.33). Adverse event rates were generally higher in non\u2011randomized studies, with hypoxemia the most frequently reported event across study types (\u2265\u200924%). Subgroup findings were consistent with overall results.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>To our knowledge, this is the first meta\u2010analysis evaluating LISA safety outcomes across both RCTs and non\u2010randomized studies. LISA demonstrates a safety profile broadly comparable to INSURE\/ETT for most outcomes. Differences observed in observational studies likely reflect variability in reporting and clinical practice. Standardized training and procedure optimization may further enhance safety.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ppul.71718","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T09:42:43Z","timestamp":1782985363000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Safety of Less Invasive Surfactant Administration in Preterm Infants: A Meta\u2010Analysis"],"prefix":"10.1002","volume":"61","author":[{"given":"Xuezheng","family":"Sun","sequence":"first","affiliation":[{"name":"Chiesi USA Inc Cary North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9683-4928","authenticated-orcid":false,"given":"Shaked","family":"Yarza","sequence":"additional","affiliation":[{"name":"Chiesi USA Inc Cary North Carolina 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