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Oscillatory mechanics at birth for identifying infants requiring surfactant: a prospective, observational trial
Current criteria for surfactant administration assume that hypoxia is a direct marker of lung-volume de-recruitment. We first introduced an early, non-invasive assessment of lung mechanics by the Forced Oscillation Technique (FOT) and evaluated its role in predicting the need for surfactant therapy....
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Published in: | Respiratory research 2021-12, Vol.22 (1), p.314-11, Article 314 |
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creator | Lavizzari, Anna Veneroni, Chiara Beretta, Francesco Ottaviani, Valeria Fumagalli, Claudia Tossici, Marta Colnaghi, Mariarosa Mosca, Fabio Dellacà, Raffaele L |
description | Current criteria for surfactant administration assume that hypoxia is a direct marker of lung-volume de-recruitment. We first introduced an early, non-invasive assessment of lung mechanics by the Forced Oscillation Technique (FOT) and evaluated its role in predicting the need for surfactant therapy.
To evaluate whether lung reactance (Xrs) assessment by FOT within 2 h of birth identifies infants who would need surfactant within 24 h; to eventually determine Xrs performance and a cut-off value for early detection of infants requiring surfactant.
We conducted a prospective, observational, non-randomized study in our tertiary NICU in Milan. Eligible infants were born between 27
and 34
weeks' gestation, presenting respiratory distress after birth.
endotracheal intubation at birth, major malformations participation in other interventional trials, parental consent denied. We assessed Xrs during nasal CPAP at 5 cmH
O at 10 Hz within 2 h of life, recording flow and pressure tracing through a Fabian Ventilator for off-line analysis. Clinicians were blinded to FOT results.
We enrolled 61 infants, with a median [IQR] gestational age of 31.9 [30.3; 32.9] weeks and birth weight 1490 [1230; 1816] g; 2 infants were excluded from the analysis for set-up malfunctioning. 14/59 infants received surfactant within 24 h. Xrs predicted surfactant need with a cut-off - 33.4 cmH
O*s/L and AUC-ROC = 0.86 (0.76-0.96), with sensitivity 0.85 and specificity 0.83. An Xrs cut-off value of - 23.3 cmH
O*s/L identified infants needing surfactant or respiratory support > 28 days with AUC-ROC = 0.89 (0.81-0.97), sensitivity 0.86 and specificity 0.77. Interestingly, 12 infants with Xrs |
doi_str_mv | 10.1186/s12931-021-01906-6 |
format | article |
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To evaluate whether lung reactance (Xrs) assessment by FOT within 2 h of birth identifies infants who would need surfactant within 24 h; to eventually determine Xrs performance and a cut-off value for early detection of infants requiring surfactant.
We conducted a prospective, observational, non-randomized study in our tertiary NICU in Milan. Eligible infants were born between 27
and 34
weeks' gestation, presenting respiratory distress after birth.
endotracheal intubation at birth, major malformations participation in other interventional trials, parental consent denied. We assessed Xrs during nasal CPAP at 5 cmH
O at 10 Hz within 2 h of life, recording flow and pressure tracing through a Fabian Ventilator for off-line analysis. Clinicians were blinded to FOT results.
We enrolled 61 infants, with a median [IQR] gestational age of 31.9 [30.3; 32.9] weeks and birth weight 1490 [1230; 1816] g; 2 infants were excluded from the analysis for set-up malfunctioning. 14/59 infants received surfactant within 24 h. Xrs predicted surfactant need with a cut-off - 33.4 cmH
O*s/L and AUC-ROC = 0.86 (0.76-0.96), with sensitivity 0.85 and specificity 0.83. An Xrs cut-off value of - 23.3 cmH
O*s/L identified infants needing surfactant or respiratory support > 28 days with AUC-ROC = 0.89 (0.81-0.97), sensitivity 0.86 and specificity 0.77. Interestingly, 12 infants with Xrs < - 23.3 cmH
O*s/L (i.e. de-recruited lungs) did not receive surfactant and subsequently required prolonged respiratory support.
Xrs assessed within 2 h of life predicts surfactant need and respiratory support duration in preterm infants. The possible role of Xrs in improving the individualization of respiratory management in preterm infants deserves further investigation.</description><identifier>ISSN: 1465-993X</identifier><identifier>ISSN: 1465-9921</identifier><identifier>EISSN: 1465-993X</identifier><identifier>EISSN: 1465-9921</identifier><identifier>DOI: 10.1186/s12931-021-01906-6</identifier><identifier>PMID: 34930247</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Birth weight ; Breathing mechanics ; Care and treatment ; Clinical outcomes ; Continuous Positive Airway Pressure ; Criteria ; Diagnosis ; Dosage and administration ; Female ; Follow-Up Studies ; Forced vibration ; Gestational Age ; Humans ; Hypoxia ; Infant, Newborn ; Infant, Premature ; Infants ; Infants (Premature) ; Intubation ; Lung - physiopathology ; Lungs ; Male ; Mechanics ; Mechanics (physics) ; Medical examination ; Nasal continuous positive airway pressure ; Neonatal respiratory distress syndrome ; Neonates ; Newborn babies ; Observational studies ; Pilot Projects ; Premature infants ; Prospective Studies ; Pulmonary surfactant ; Pulmonary Surfactants - administration & dosage ; Reactance ; Respiratory distress syndrome ; Respiratory Distress Syndrome, Newborn - physiopathology ; Respiratory Distress Syndrome, Newborn - therapy ; Respiratory system ; Risk factors ; Sensitivity ; Surfactants ; Testing ; Variables ; Ventilators</subject><ispartof>Respiratory research, 2021-12, Vol.22 (1), p.314-11, Article 314</ispartof><rights>2021. The Author(s).</rights><rights>COPYRIGHT 2021 BioMed Central Ltd.</rights><rights>2021. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>The Author(s) 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c563t-82c21f47f51886aabfaf823feffbb4b91d060f60698eb5631623c334504828573</citedby><cites>FETCH-LOGICAL-c563t-82c21f47f51886aabfaf823feffbb4b91d060f60698eb5631623c334504828573</cites><orcidid>0000-0001-5529-0787</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8686669/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2620937397?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34930247$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lavizzari, Anna</creatorcontrib><creatorcontrib>Veneroni, Chiara</creatorcontrib><creatorcontrib>Beretta, Francesco</creatorcontrib><creatorcontrib>Ottaviani, Valeria</creatorcontrib><creatorcontrib>Fumagalli, Claudia</creatorcontrib><creatorcontrib>Tossici, Marta</creatorcontrib><creatorcontrib>Colnaghi, Mariarosa</creatorcontrib><creatorcontrib>Mosca, Fabio</creatorcontrib><creatorcontrib>Dellacà, Raffaele L</creatorcontrib><title>Oscillatory mechanics at birth for identifying infants requiring surfactant: a prospective, observational trial</title><title>Respiratory research</title><addtitle>Respir Res</addtitle><description>Current criteria for surfactant administration assume that hypoxia is a direct marker of lung-volume de-recruitment. We first introduced an early, non-invasive assessment of lung mechanics by the Forced Oscillation Technique (FOT) and evaluated its role in predicting the need for surfactant therapy.
To evaluate whether lung reactance (Xrs) assessment by FOT within 2 h of birth identifies infants who would need surfactant within 24 h; to eventually determine Xrs performance and a cut-off value for early detection of infants requiring surfactant.
We conducted a prospective, observational, non-randomized study in our tertiary NICU in Milan. Eligible infants were born between 27
and 34
weeks' gestation, presenting respiratory distress after birth.
endotracheal intubation at birth, major malformations participation in other interventional trials, parental consent denied. We assessed Xrs during nasal CPAP at 5 cmH
O at 10 Hz within 2 h of life, recording flow and pressure tracing through a Fabian Ventilator for off-line analysis. Clinicians were blinded to FOT results.
We enrolled 61 infants, with a median [IQR] gestational age of 31.9 [30.3; 32.9] weeks and birth weight 1490 [1230; 1816] g; 2 infants were excluded from the analysis for set-up malfunctioning. 14/59 infants received surfactant within 24 h. Xrs predicted surfactant need with a cut-off - 33.4 cmH
O*s/L and AUC-ROC = 0.86 (0.76-0.96), with sensitivity 0.85 and specificity 0.83. An Xrs cut-off value of - 23.3 cmH
O*s/L identified infants needing surfactant or respiratory support > 28 days with AUC-ROC = 0.89 (0.81-0.97), sensitivity 0.86 and specificity 0.77. Interestingly, 12 infants with Xrs < - 23.3 cmH
O*s/L (i.e. de-recruited lungs) did not receive surfactant and subsequently required prolonged respiratory support.
Xrs assessed within 2 h of life predicts surfactant need and respiratory support duration in preterm infants. The possible role of Xrs in improving the individualization of respiratory management in preterm infants deserves further investigation.</description><subject>Birth weight</subject><subject>Breathing mechanics</subject><subject>Care and treatment</subject><subject>Clinical outcomes</subject><subject>Continuous Positive Airway Pressure</subject><subject>Criteria</subject><subject>Diagnosis</subject><subject>Dosage and administration</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Forced vibration</subject><subject>Gestational Age</subject><subject>Humans</subject><subject>Hypoxia</subject><subject>Infant, Newborn</subject><subject>Infant, Premature</subject><subject>Infants</subject><subject>Infants (Premature)</subject><subject>Intubation</subject><subject>Lung - physiopathology</subject><subject>Lungs</subject><subject>Male</subject><subject>Mechanics</subject><subject>Mechanics (physics)</subject><subject>Medical examination</subject><subject>Nasal continuous positive airway pressure</subject><subject>Neonatal respiratory distress syndrome</subject><subject>Neonates</subject><subject>Newborn babies</subject><subject>Observational studies</subject><subject>Pilot Projects</subject><subject>Premature infants</subject><subject>Prospective Studies</subject><subject>Pulmonary surfactant</subject><subject>Pulmonary Surfactants - administration & dosage</subject><subject>Reactance</subject><subject>Respiratory distress syndrome</subject><subject>Respiratory Distress Syndrome, Newborn - physiopathology</subject><subject>Respiratory Distress Syndrome, Newborn - therapy</subject><subject>Respiratory system</subject><subject>Risk factors</subject><subject>Sensitivity</subject><subject>Surfactants</subject><subject>Testing</subject><subject>Variables</subject><subject>Ventilators</subject><issn>1465-993X</issn><issn>1465-9921</issn><issn>1465-993X</issn><issn>1465-9921</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNptUl1rFDEUHUSxH_oHfJCALz44NV-TSXwolGK1UOiLgm_hTibZzTIz2SaZhf33Zndr7YqEkHByzrncm1NV7wi-IESKz4lQxUiNadlEYVGLF9Up4aKplWK_Xj67n1RnKa0wJq1sm9fVCeOKYcrb0yrcJ-OHAXKIWzRas4TJm4Qgo87HvEQuROR7O2Xvtn5aID85mHJC0T7MPu6QNEcHJhf0CwK0jiGtrcl-Yz-h0CUbN5B9mGBAOXoY3lSvHAzJvn08z6ufN19_XH-v7-6_3V5f3dWmESzXkhpKHG9dQ6QUAJ0DJylz1rmu450iPRbYCSyUtF1REEGZYYw3mEsqm5adV7cH3z7ASq-jHyFudQCv90CICw0xezNYTYwBJ3qsFAaOse2UhKYF1RJqubRQvC4PXuu5G21vyjQiDEemxy-TX-pF2GgppBBCFYOPjwYxPMw2ZT36ZGwZ-2TDnDQVhDLJOcWF-uEf6irMsYxvx6JYsZap9i9rAaWB8ieh1DU7U31V6gki2j3r4j-ssno7ehMm63zBjwT0IDDlF1O07qlHgvUucvoQOV0ip_eR06KI3j-fzpPkT8bYbz1K0pQ</recordid><startdate>20211220</startdate><enddate>20211220</enddate><creator>Lavizzari, Anna</creator><creator>Veneroni, Chiara</creator><creator>Beretta, Francesco</creator><creator>Ottaviani, Valeria</creator><creator>Fumagalli, Claudia</creator><creator>Tossici, Marta</creator><creator>Colnaghi, Mariarosa</creator><creator>Mosca, Fabio</creator><creator>Dellacà, Raffaele L</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><general>BMC</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7U7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0001-5529-0787</orcidid></search><sort><creationdate>20211220</creationdate><title>Oscillatory mechanics at birth for identifying infants requiring surfactant: a prospective, observational trial</title><author>Lavizzari, Anna ; Veneroni, Chiara ; Beretta, Francesco ; Ottaviani, Valeria ; Fumagalli, Claudia ; Tossici, Marta ; Colnaghi, Mariarosa ; Mosca, Fabio ; Dellacà, Raffaele L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c563t-82c21f47f51886aabfaf823feffbb4b91d060f60698eb5631623c334504828573</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Birth weight</topic><topic>Breathing mechanics</topic><topic>Care and treatment</topic><topic>Clinical outcomes</topic><topic>Continuous Positive Airway Pressure</topic><topic>Criteria</topic><topic>Diagnosis</topic><topic>Dosage and administration</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Forced vibration</topic><topic>Gestational Age</topic><topic>Humans</topic><topic>Hypoxia</topic><topic>Infant, Newborn</topic><topic>Infant, Premature</topic><topic>Infants</topic><topic>Infants (Premature)</topic><topic>Intubation</topic><topic>Lung - physiopathology</topic><topic>Lungs</topic><topic>Male</topic><topic>Mechanics</topic><topic>Mechanics (physics)</topic><topic>Medical examination</topic><topic>Nasal continuous positive airway pressure</topic><topic>Neonatal respiratory distress syndrome</topic><topic>Neonates</topic><topic>Newborn babies</topic><topic>Observational studies</topic><topic>Pilot Projects</topic><topic>Premature infants</topic><topic>Prospective Studies</topic><topic>Pulmonary surfactant</topic><topic>Pulmonary Surfactants - administration & dosage</topic><topic>Reactance</topic><topic>Respiratory distress syndrome</topic><topic>Respiratory Distress Syndrome, Newborn - physiopathology</topic><topic>Respiratory Distress Syndrome, Newborn - therapy</topic><topic>Respiratory system</topic><topic>Risk factors</topic><topic>Sensitivity</topic><topic>Surfactants</topic><topic>Testing</topic><topic>Variables</topic><topic>Ventilators</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lavizzari, Anna</creatorcontrib><creatorcontrib>Veneroni, Chiara</creatorcontrib><creatorcontrib>Beretta, Francesco</creatorcontrib><creatorcontrib>Ottaviani, Valeria</creatorcontrib><creatorcontrib>Fumagalli, Claudia</creatorcontrib><creatorcontrib>Tossici, Marta</creatorcontrib><creatorcontrib>Colnaghi, Mariarosa</creatorcontrib><creatorcontrib>Mosca, Fabio</creatorcontrib><creatorcontrib>Dellacà, Raffaele L</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Publicly Available Content Database (Proquest) (PQ_SDU_P3)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals</collection><jtitle>Respiratory research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lavizzari, Anna</au><au>Veneroni, Chiara</au><au>Beretta, Francesco</au><au>Ottaviani, Valeria</au><au>Fumagalli, Claudia</au><au>Tossici, Marta</au><au>Colnaghi, Mariarosa</au><au>Mosca, Fabio</au><au>Dellacà, Raffaele L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Oscillatory mechanics at birth for identifying infants requiring surfactant: a prospective, observational trial</atitle><jtitle>Respiratory research</jtitle><addtitle>Respir Res</addtitle><date>2021-12-20</date><risdate>2021</risdate><volume>22</volume><issue>1</issue><spage>314</spage><epage>11</epage><pages>314-11</pages><artnum>314</artnum><issn>1465-993X</issn><issn>1465-9921</issn><eissn>1465-993X</eissn><eissn>1465-9921</eissn><abstract>Current criteria for surfactant administration assume that hypoxia is a direct marker of lung-volume de-recruitment. We first introduced an early, non-invasive assessment of lung mechanics by the Forced Oscillation Technique (FOT) and evaluated its role in predicting the need for surfactant therapy.
To evaluate whether lung reactance (Xrs) assessment by FOT within 2 h of birth identifies infants who would need surfactant within 24 h; to eventually determine Xrs performance and a cut-off value for early detection of infants requiring surfactant.
We conducted a prospective, observational, non-randomized study in our tertiary NICU in Milan. Eligible infants were born between 27
and 34
weeks' gestation, presenting respiratory distress after birth.
endotracheal intubation at birth, major malformations participation in other interventional trials, parental consent denied. We assessed Xrs during nasal CPAP at 5 cmH
O at 10 Hz within 2 h of life, recording flow and pressure tracing through a Fabian Ventilator for off-line analysis. Clinicians were blinded to FOT results.
We enrolled 61 infants, with a median [IQR] gestational age of 31.9 [30.3; 32.9] weeks and birth weight 1490 [1230; 1816] g; 2 infants were excluded from the analysis for set-up malfunctioning. 14/59 infants received surfactant within 24 h. Xrs predicted surfactant need with a cut-off - 33.4 cmH
O*s/L and AUC-ROC = 0.86 (0.76-0.96), with sensitivity 0.85 and specificity 0.83. An Xrs cut-off value of - 23.3 cmH
O*s/L identified infants needing surfactant or respiratory support > 28 days with AUC-ROC = 0.89 (0.81-0.97), sensitivity 0.86 and specificity 0.77. Interestingly, 12 infants with Xrs < - 23.3 cmH
O*s/L (i.e. de-recruited lungs) did not receive surfactant and subsequently required prolonged respiratory support.
Xrs assessed within 2 h of life predicts surfactant need and respiratory support duration in preterm infants. The possible role of Xrs in improving the individualization of respiratory management in preterm infants deserves further investigation.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>34930247</pmid><doi>10.1186/s12931-021-01906-6</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0001-5529-0787</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Birth weight Breathing mechanics Care and treatment Clinical outcomes Continuous Positive Airway Pressure Criteria Diagnosis Dosage and administration Female Follow-Up Studies Forced vibration Gestational Age Humans Hypoxia Infant, Newborn Infant, Premature Infants Infants (Premature) Intubation Lung - physiopathology Lungs Male Mechanics Mechanics (physics) Medical examination Nasal continuous positive airway pressure Neonatal respiratory distress syndrome Neonates Newborn babies Observational studies Pilot Projects Premature infants Prospective Studies Pulmonary surfactant Pulmonary Surfactants - administration & dosage Reactance Respiratory distress syndrome Respiratory Distress Syndrome, Newborn - physiopathology Respiratory Distress Syndrome, Newborn - therapy Respiratory system Risk factors Sensitivity Surfactants Testing Variables Ventilators |
title | Oscillatory mechanics at birth for identifying infants requiring surfactant: a prospective, observational trial |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-03T02%3A44%3A13IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_doaj_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Oscillatory%20mechanics%20at%20birth%20for%20identifying%20infants%20requiring%20surfactant:%20a%20prospective,%20observational%20trial&rft.jtitle=Respiratory%20research&rft.au=Lavizzari,%20Anna&rft.date=2021-12-20&rft.volume=22&rft.issue=1&rft.spage=314&rft.epage=11&rft.pages=314-11&rft.artnum=314&rft.issn=1465-993X&rft.eissn=1465-993X&rft_id=info:doi/10.1186/s12931-021-01906-6&rft_dat=%3Cgale_doaj_%3EA693616797%3C/gale_doaj_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c563t-82c21f47f51886aabfaf823feffbb4b91d060f60698eb5631623c334504828573%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2620937397&rft_id=info:pmid/34930247&rft_galeid=A693616797&rfr_iscdi=true |