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We aim to fill these knowledge gaps.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Systematic and pragmatic review coupled with meta-analysis of randomized controlled trials of bovine or porcine surfactants administered to treat RDS in preterm neonates; common extra-pulmonary neonatal intensive care outcomes were considered. As additional analysis, animal or human translational studies about mechanisms linking surfactant replacement to extra-pulmonary neonatal outcomes were also systematically reviewed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Porcine surfactant is associated with lower incidence of patent<jats:italic>ductus arteriosus<\/jats:italic>(OR:0.655; 95%CI:0.460\u20130.931);<jats:italic>p<\/jats:italic>\u2009=\u20090.018; 12 trials; 1472 patients); prenatal steroids (coeff.:-0.009, 95%CI:-0.03\u20130.009,<jats:italic>p<\/jats:italic>\u2009=\u20090.323) and gestational age (coeff.:0.079, 95%CI:-0.18\u20130.34,<jats:italic>p<\/jats:italic>\u2009=\u20090.554) did not influence this effect size. No significant differences were found between porcine and bovine surfactants on neonatal intensive care unit length of stay (mean difference (days):-2.977; 95%CI:-6.659\u20130.705;<jats:italic>p<\/jats:italic>\u2009=\u20090.113; 8 trials; 855 patients), intra-ventricular hemorrhage of any grade (OR:0.860; 95%CI:0.648\u20131.139);<jats:italic>p<\/jats:italic>\u2009=\u20090.293; 15 trials; 1703 patients), severe intra-ventricular hemorrhage (OR:0.852; 95%CI:0.624\u20131.163);<jats:italic>p<\/jats:italic>\u2009=\u20090.313; 15 trials; 1672 patients), necrotizing entero-colitis (OR:1.190; 95%CI:0.785\u20131.803);<jats:italic>p<\/jats:italic>\u2009=\u20090.412; 9 trials; 1097 patients) and retinopathy of prematurity (OR:0.801; 95%CI:0.480\u20131.337);<jats:italic>p<\/jats:italic>\u2009=\u20090.396; 10 trials; 962 patients).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Physiopathological mechanisms explaining the effect of surfactant have been found for patent<jats:italic>ductus arteriosus<\/jats:italic>only, while they are lacking for all other endpoints. Porcine surfactant is associated with lower incidence of PDA than bovine surfactants. As there are no differences in terms of other extra-pulmonary outcomes and no physiopathological plausibility, these endpoints should not be used in future trials.<\/jats:p><\/jats:sec><jats:sec><jats:title>Registration<\/jats:title><jats:p>PROSPERO n.<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.crd.york.ac.uk\/PROSPERO\/display_record.php?RecordID=100906\">CRD42018100906<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12931-019-1267-8","type":"journal-article","created":{"date-parts":[[2020,1,7]],"date-time":"2020-01-07T15:03:37Z","timestamp":1578409417000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Porcine versus bovine surfactant therapy for RDS in preterm neonates: pragmatic meta-analysis and review of physiopathological plausibility of the effects on extra-pulmonary outcomes"],"prefix":"10.1186","volume":"21","author":[{"given":"Silvia","family":"Foligno","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3846-4834","authenticated-orcid":false,"given":"Daniele","family":"De Luca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,1,7]]},"reference":[{"issue":"4","key":"1267_CR1","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1002\/ppul.24241","volume":"54","author":"Keyur Donda","year":"2019","unstructured":"Donda K, Vijayakanthi N, Dapaah-Siakwan F, Bhatt P, Rastogi D, Rastogi S. 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Trials meta-analysed have all received their original ethical approval.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"A\/Prof. D. De Luca has received grants for research and educational projects from Chiesi Pharmaceuticals spa and ABBVIE inc. He also received travel grants from ABBVIE inc. He served as consultant and lecturer for both Chiesi Pharmaceuticals spa and ABBVIE inc. Finally, he was member of the advisory boards for both Chiesi Pharmaceuticals spa and ABBVIE inc. These companies produce two surfactants analyzed in the paper, but they had no role in design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review, approval of the manuscript or decision to submit it for publication.The other author declares no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"8"}}