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With the advent of less-invasive surfactant delivery techniques that minimize or eliminate exposure to invasive mechanical ventilation, the question of prophylactic surfactant administration has reemerged. This review discusses the evidence for less-invasive surfactant therapy applied prophylactically. In summary, prophylactic surfactant administration by pharyngeal deposition or brief intubation are not recommended. Surfactant delivery via supraglottic airway or by aerosolization have not been investigated as prophylaxis for RDS. Recent evidence suggests that prophylactic surfactant administration via thin catheter is safe and effective. Several ongoing randomized clinical trials are further evaluating the efficacy of prophylactic surfactant administration via thin catheter. Prophylactic surfactant administration via supraglottic airway devices and aerosolization should be evaluated in future studies.<\/jats:p>","DOI":"10.1038\/s41372-025-02420-z","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T09:12:42Z","timestamp":1758618762000},"page":"1-5","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Prophylactic surfactant therapy in the era of less invasive surfactant delivery"],"prefix":"10.1038","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8334-6282","authenticated-orcid":false,"given":"Dinushan C.","family":"Kaluarachchi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9352-0934","authenticated-orcid":false,"given":"Anup","family":"Katheria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9724-9456","authenticated-orcid":false,"given":"Patrick J.","family":"Peebles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9703-5266","authenticated-orcid":false,"given":"Scott O.","family":"Guthrie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5337-5610","authenticated-orcid":false,"given":"Venkatakrishna","family":"Kakkilaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4142-477X","authenticated-orcid":false,"given":"Peter A.","family":"Dargaville","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,23]]},"reference":[{"key":"2420_CR1","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1542\/pir.12.9.261","volume":"12","author":"RF Soll","year":"1991","unstructured":"Soll RF, Lucey JF. 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Dr. Kakkilaya has received grant support from Chiesi Pharmaceuticals and SPARK Biomedical, Inc. Dr Dargaville is supported by Investigator Grant 2033989 from the Australian National Health and Medical Research Council. Dr Dargaville reported receiving travel support from Chiesi Pharmaceuticals and SLE Limited; in addition, Dr Dargaville has a design patent for a surfactant administration catheter (USD752215S) issued. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}