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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Inhaled Nitric Oxide in Preterm Infants: An Individual-Patient Data Meta-analysis of Randomized Trials</title><author><name sortKey="Askie, Lisa M" sort="Askie, Lisa M" uniqKey="Askie L" first="Lisa M." last="Askie">Lisa M. Askie</name><affiliation><nlm:aff id="aff1">National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, Australia;</nlm:aff></affiliation></author><author><name sortKey="Ballard, Roberta A" sort="Ballard, Roberta A" uniqKey="Ballard R" first="Roberta A." last="Ballard">Roberta A. Ballard</name><affiliation><nlm:aff id="aff2">Department of Pediatrics, University of California at San Francisco, School of Medicine, San Francisco, California;</nlm:aff></affiliation></author><author><name sortKey="Cutter, Gary R" sort="Cutter, Gary R" uniqKey="Cutter G" first="Gary R." last="Cutter">Gary R. Cutter</name><affiliation><nlm:aff id="aff3">School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama;</nlm:aff></affiliation></author><author><name sortKey="Dani, Carlo" sort="Dani, Carlo" uniqKey="Dani C" first="Carlo" last="Dani">Carlo Dani</name><affiliation><nlm:aff id="aff4">Section of Neonatology, Department of Surgical and Medical Critical Care, Careggi University Hospital of Florence, Florence, Italy;</nlm:aff></affiliation></author><author><name sortKey="Elbourne, Diana" sort="Elbourne, Diana" uniqKey="Elbourne D" first="Diana" last="Elbourne">Diana Elbourne</name><affiliation><nlm:aff id="aff5">Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Field, David" sort="Field, David" uniqKey="Field D" first="David" last="Field">David Field</name><affiliation><nlm:aff id="aff6">Department of Health Science, University of Leicester, Leicester, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Hascoet, Jean Michel" sort="Hascoet, Jean Michel" uniqKey="Hascoet J" first="Jean-Michel" last="Hascoet">Jean-Michel Hascoet</name><affiliation><nlm:aff id="aff7">Neonatology, Maternite Regionale Universitaire, Nancy, France;</nlm:aff></affiliation></author><author><name sortKey="Hibbs, Anna Maria" sort="Hibbs, Anna Maria" uniqKey="Hibbs A" first="Anna Maria" last="Hibbs">Anna Maria Hibbs</name><affiliation><nlm:aff id="aff8">Department of Pediatrics, Case Western Reserve University and Rainbow Babies & Children's Hospital, Cleveland, Ohio;</nlm:aff></affiliation></author><author><name sortKey="Kinsella, John P" sort="Kinsella, John P" uniqKey="Kinsella J" first="John P." last="Kinsella">John P. Kinsella</name><affiliation><nlm:aff id="aff9">Department of Pediatrics, University of Colorado School of Medicine, Denver, Colorado;</nlm:aff></affiliation></author><author><name sortKey="Mercier, Jean Christophe" sort="Mercier, Jean Christophe" uniqKey="Mercier J" first="Jean-Christophe" last="Mercier">Jean-Christophe Mercier</name><affiliation><nlm:aff id="aff10">Department of Pediatric Emergency Medicine, Hôpital Robert Debré, Université Paris-7 Denis Diderot, Paris, France;</nlm:aff></affiliation></author><author><name sortKey="Rich, Wade" sort="Rich, Wade" uniqKey="Rich W" first="Wade" last="Rich">Wade Rich</name><affiliation><nlm:aff id="aff11">Division of Neonatology, University of California, San Diego, California;</nlm:aff></affiliation></author><author><name sortKey="Schreiber, Michael D" sort="Schreiber, Michael D" uniqKey="Schreiber M" first="Michael D." last="Schreiber">Michael D. Schreiber</name><affiliation><nlm:aff id="aff12">Department of Pediatrics, University of Chicago, Chicago, Illinois;</nlm:aff></affiliation></author><author><name sortKey="Wongsiridej, Pimol Srisuparp" sort="Wongsiridej, Pimol Srisuparp" uniqKey="Wongsiridej P" first="Pimol Srisuparp" last="Wongsiridej">Pimol Srisuparp Wongsiridej</name><affiliation><nlm:aff id="aff13">Division of Neonatology, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand;</nlm:aff></affiliation></author><author><name sortKey="Subhedar, Nim V" sort="Subhedar, Nim V" uniqKey="Subhedar N" first="Nim V." last="Subhedar">Nim V. Subhedar</name><affiliation><nlm:aff id="aff14">Neonatal Unit, Liverpool Women's Hospital, Liverpool, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Van Meurs, Krisa P" sort="Van Meurs, Krisa P" uniqKey="Van Meurs K" first="Krisa P." last="Van Meurs">Krisa P. Van Meurs</name><affiliation><nlm:aff id="aff15">Division of Neonatal and Developmental Medicine, Stanford University School of Medicine and Lucile Salter Packard Children's Hospital, Palo Alto, California;</nlm:aff></affiliation></author><author><name sortKey="Voysey, Merryn" sort="Voysey, Merryn" uniqKey="Voysey M" first="Merryn" last="Voysey">Merryn Voysey</name><affiliation><nlm:aff id="aff1">National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, Australia;</nlm:aff></affiliation></author><author><name sortKey="Barrington, Keith" sort="Barrington, Keith" uniqKey="Barrington K" first="Keith" last="Barrington">Keith Barrington</name><affiliation><nlm:aff wicri:cut="; and" id="aff16">Division of Neonatology, Centre Hospitalier Universitaire Ste-Justine, Montreal, Quebec, Canada</nlm:aff></affiliation></author><author><name sortKey="Ehrenkranz, Richard A" sort="Ehrenkranz, Richard A" uniqKey="Ehrenkranz R" first="Richard A." last="Ehrenkranz">Richard A. Ehrenkranz</name><affiliation><nlm:aff id="aff17">Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut</nlm:aff></affiliation></author><author><name sortKey="Finer, Neil N" sort="Finer, Neil N" uniqKey="Finer N" first="Neil N." last="Finer">Neil N. Finer</name><affiliation><nlm:aff id="aff11">Division of Neonatology, University of California, San Diego, California;</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">21930540</idno><idno type="pmc">3387905</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3387905</idno><idno type="RBID">PMC:3387905</idno><idno type="doi">10.1542/peds.2010-2725</idno><date when="2011">2011</date><idno type="wicri:Area/Pmc/Corpus">002E97</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002E97</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Inhaled Nitric Oxide in Preterm Infants: An Individual-Patient Data Meta-analysis of Randomized Trials</title><author><name sortKey="Askie, Lisa M" sort="Askie, Lisa M" uniqKey="Askie L" first="Lisa M." last="Askie">Lisa M. Askie</name><affiliation><nlm:aff id="aff1">National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, Australia;</nlm:aff></affiliation></author><author><name sortKey="Ballard, Roberta A" sort="Ballard, Roberta A" uniqKey="Ballard R" first="Roberta A." last="Ballard">Roberta A. Ballard</name><affiliation><nlm:aff id="aff2">Department of Pediatrics, University of California at San Francisco, School of Medicine, San Francisco, California;</nlm:aff></affiliation></author><author><name sortKey="Cutter, Gary R" sort="Cutter, Gary R" uniqKey="Cutter G" first="Gary R." last="Cutter">Gary R. Cutter</name><affiliation><nlm:aff id="aff3">School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama;</nlm:aff></affiliation></author><author><name sortKey="Dani, Carlo" sort="Dani, Carlo" uniqKey="Dani C" first="Carlo" last="Dani">Carlo Dani</name><affiliation><nlm:aff id="aff4">Section of Neonatology, Department of Surgical and Medical Critical Care, Careggi University Hospital of Florence, Florence, Italy;</nlm:aff></affiliation></author><author><name sortKey="Elbourne, Diana" sort="Elbourne, Diana" uniqKey="Elbourne D" first="Diana" last="Elbourne">Diana Elbourne</name><affiliation><nlm:aff id="aff5">Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Field, David" sort="Field, David" uniqKey="Field D" first="David" last="Field">David Field</name><affiliation><nlm:aff id="aff6">Department of Health Science, University of Leicester, Leicester, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Hascoet, Jean Michel" sort="Hascoet, Jean Michel" uniqKey="Hascoet J" first="Jean-Michel" last="Hascoet">Jean-Michel Hascoet</name><affiliation><nlm:aff id="aff7">Neonatology, Maternite Regionale Universitaire, Nancy, France;</nlm:aff></affiliation></author><author><name sortKey="Hibbs, Anna Maria" sort="Hibbs, Anna Maria" uniqKey="Hibbs A" first="Anna Maria" last="Hibbs">Anna Maria Hibbs</name><affiliation><nlm:aff id="aff8">Department of Pediatrics, Case Western Reserve University and Rainbow Babies & Children's Hospital, Cleveland, Ohio;</nlm:aff></affiliation></author><author><name sortKey="Kinsella, John P" sort="Kinsella, John P" uniqKey="Kinsella J" first="John P." last="Kinsella">John P. Kinsella</name><affiliation><nlm:aff id="aff9">Department of Pediatrics, University of Colorado School of Medicine, Denver, Colorado;</nlm:aff></affiliation></author><author><name sortKey="Mercier, Jean Christophe" sort="Mercier, Jean Christophe" uniqKey="Mercier J" first="Jean-Christophe" last="Mercier">Jean-Christophe Mercier</name><affiliation><nlm:aff id="aff10">Department of Pediatric Emergency Medicine, Hôpital Robert Debré, Université Paris-7 Denis Diderot, Paris, France;</nlm:aff></affiliation></author><author><name sortKey="Rich, Wade" sort="Rich, Wade" uniqKey="Rich W" first="Wade" last="Rich">Wade Rich</name><affiliation><nlm:aff id="aff11">Division of Neonatology, University of California, San Diego, California;</nlm:aff></affiliation></author><author><name sortKey="Schreiber, Michael D" sort="Schreiber, Michael D" uniqKey="Schreiber M" first="Michael D." last="Schreiber">Michael D. Schreiber</name><affiliation><nlm:aff id="aff12">Department of Pediatrics, University of Chicago, Chicago, Illinois;</nlm:aff></affiliation></author><author><name sortKey="Wongsiridej, Pimol Srisuparp" sort="Wongsiridej, Pimol Srisuparp" uniqKey="Wongsiridej P" first="Pimol Srisuparp" last="Wongsiridej">Pimol Srisuparp Wongsiridej</name><affiliation><nlm:aff id="aff13">Division of Neonatology, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand;</nlm:aff></affiliation></author><author><name sortKey="Subhedar, Nim V" sort="Subhedar, Nim V" uniqKey="Subhedar N" first="Nim V." last="Subhedar">Nim V. Subhedar</name><affiliation><nlm:aff id="aff14">Neonatal Unit, Liverpool Women's Hospital, Liverpool, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Van Meurs, Krisa P" sort="Van Meurs, Krisa P" uniqKey="Van Meurs K" first="Krisa P." last="Van Meurs">Krisa P. Van Meurs</name><affiliation><nlm:aff id="aff15">Division of Neonatal and Developmental Medicine, Stanford University School of Medicine and Lucile Salter Packard Children's Hospital, Palo Alto, California;</nlm:aff></affiliation></author><author><name sortKey="Voysey, Merryn" sort="Voysey, Merryn" uniqKey="Voysey M" first="Merryn" last="Voysey">Merryn Voysey</name><affiliation><nlm:aff id="aff1">National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, Australia;</nlm:aff></affiliation></author><author><name sortKey="Barrington, Keith" sort="Barrington, Keith" uniqKey="Barrington K" first="Keith" last="Barrington">Keith Barrington</name><affiliation><nlm:aff wicri:cut="; and" id="aff16">Division of Neonatology, Centre Hospitalier Universitaire Ste-Justine, Montreal, Quebec, Canada</nlm:aff></affiliation></author><author><name sortKey="Ehrenkranz, Richard A" sort="Ehrenkranz, Richard A" uniqKey="Ehrenkranz R" first="Richard A." last="Ehrenkranz">Richard A. Ehrenkranz</name><affiliation><nlm:aff id="aff17">Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut</nlm:aff></affiliation></author><author><name sortKey="Finer, Neil N" sort="Finer, Neil N" uniqKey="Finer N" first="Neil N." last="Finer">Neil N. Finer</name><affiliation><nlm:aff id="aff11">Division of Neonatology, University of California, San Diego, California;</nlm:aff></affiliation></author></analytic><series><title level="j">Pediatrics</title><idno type="ISSN">0031-4005</idno><idno type="eISSN">1098-4275</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>BACKGROUND:</title><p>Inhaled nitric oxide (iNO) is an effective therapy for pulmonary hypertension and hypoxic respiratory failure in term infants. Fourteen randomized controlled trials (<italic>n</italic> = 3430 infants) have been conducted on preterm infants at risk for chronic lung disease (CLD). The study results seem contradictory.</p></sec><sec><title>DESIGN/METHODS:</title><p>Individual-patient data meta-analysis included randomized controlled trials of preterm infants (<37 weeks' gestation). Outcomes were adjusted for trial differences and correlation between siblings.</p></sec><sec><title>RESULTS:</title><p>Data from 3298 infants in 12 trials (96%) were analyzed. There was no statistically significant effect of iNO on death or CLD (59% vs 61%: relative risk [RR]: 0.96 [95% confidence interval (CI): 0.92–1.01]; <italic>P</italic> = .11) or severe neurologic events on imaging (25% vs 23%: RR: 1.12 [95% CI: 0.98–1.28]; <italic>P</italic> = .09). There were no statistically significant differences in iNO effect according to any of the patient-level characteristics tested. In trials that used a starting iNO dose of >5 vs ≤5 ppm there was evidence of improved outcome (interaction <italic>P</italic> = .02); however, these differences were not observed at other levels of exposure to iNO. This result was driven primarily by 1 trial, which also differed according to overall dose, duration, timing, and indication for treatment; a significant reduction in death or CLD (RR: 0.85 [95% CI: 0.74–0.98]) was found.</p></sec><sec><title>CONCLUSIONS:</title><p>Routine use of iNO for treatment of respiratory failure in preterm infants cannot be recommended. The use of a higher starting dose might be associated with improved outcome, but because there were differences in the designs of these trials, it requires further examination.</p></sec></div></front></TEI><pmc article-type="review-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Pediatrics</journal-id><journal-id journal-id-type="iso-abbrev">Pediatrics</journal-id><journal-id journal-id-type="hwp">pediatrics</journal-id><journal-id journal-id-type="pmc">pediatrics</journal-id><journal-id journal-id-type="publisher-id">Pediatrics</journal-id><journal-title-group><journal-title>Pediatrics</journal-title></journal-title-group><issn pub-type="ppub">0031-4005</issn><issn pub-type="epub">1098-4275</issn><publisher><publisher-name>American Academy of Pediatrics</publisher-name><publisher-loc>Elk Grove Village, IL, USA</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">21930540</article-id><article-id pub-id-type="pmc">3387905</article-id><article-id pub-id-type="publisher-id">2010-2725</article-id><article-id pub-id-type="doi">10.1542/peds.2010-2725</article-id><article-categories><subj-group subj-group-type="hwp-journal-coll"><subject>1</subject></subj-group><subj-group subj-group-type="heading"><subject>Review Articles</subject></subj-group></article-categories><title-group><article-title>Inhaled Nitric Oxide in Preterm Infants: An Individual-Patient Data Meta-analysis of Randomized Trials</article-title></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name><surname>Askie</surname><given-names>Lisa M.</given-names></name><degrees>PhD, MPH</degrees><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ballard</surname><given-names>Roberta A.</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Cutter</surname><given-names>Gary R.</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="aff3"><sup>c</sup></xref></contrib><contrib contrib-type="author"><name><surname>Dani</surname><given-names>Carlo</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="aff4"><sup>d</sup></xref></contrib><contrib contrib-type="author"><name><surname>Elbourne</surname><given-names>Diana</given-names></name><degrees>BSc(Soc), MSc(Stats), PhD</degrees><xref ref-type="aff" rid="aff5"><sup>e</sup></xref></contrib><contrib contrib-type="author"><name><surname>Field</surname><given-names>David</given-names></name><degrees>FRCPCH, DM</degrees><xref ref-type="aff" rid="aff6"><sup>f</sup></xref></contrib><contrib contrib-type="author"><name><surname>Hascoet</surname><given-names>Jean-Michel</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="aff7"><sup>g</sup></xref></contrib><contrib contrib-type="author"><name><surname>Hibbs</surname><given-names>Anna Maria</given-names></name><degrees>MD, MSCE</degrees><xref ref-type="aff" rid="aff8"><sup>h</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kinsella</surname><given-names>John P.</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="aff9"><sup>i</sup></xref></contrib><contrib contrib-type="author"><name><surname>Mercier</surname><given-names>Jean-Christophe</given-names></name><degrees>MS, MSci</degrees><xref ref-type="aff" rid="aff10"><sup>j</sup></xref></contrib><contrib contrib-type="author"><name><surname>Rich</surname><given-names>Wade</given-names></name><degrees>BSHS, RRT</degrees><xref ref-type="aff" rid="aff11"><sup>k</sup></xref></contrib><contrib contrib-type="author"><name><surname>Schreiber</surname><given-names>Michael D.</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="aff12"><sup>l</sup></xref></contrib><contrib contrib-type="author"><name><surname>Wongsiridej</surname><given-names>Pimol (Srisuparp)</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="aff13"><sup>m</sup></xref></contrib><contrib contrib-type="author"><name><surname>Subhedar</surname><given-names>Nim V.</given-names></name><degrees>MBChB, FRCPCH, MD</degrees><xref ref-type="aff" rid="aff14"><sup>n</sup></xref></contrib><contrib contrib-type="author"><name><surname>Van Meurs</surname><given-names>Krisa P.</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="aff15"><sup>o</sup></xref></contrib><contrib contrib-type="author"><name><surname>Voysey</surname><given-names>Merryn</given-names></name><degrees>MBiostat</degrees><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Barrington</surname><given-names>Keith</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="aff16"><sup>p</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ehrenkranz</surname><given-names>Richard A.</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="aff17"><sup>q</sup></xref></contrib><contrib contrib-type="author"><name><surname>Finer</surname><given-names>Neil N.</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="aff11"><sup>k</sup></xref></contrib><contrib contrib-type="author"><collab>on behalf of the Meta-analysis of Preterm Patients on Inhaled Nitric Oxide (MAPPiNO) Collaboration</collab></contrib><aff id="aff1"><label>a</label>National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, Australia;</aff><aff id="aff2"><label>b</label>Department of Pediatrics, University of California at San Francisco, School of Medicine, San Francisco, California;</aff><aff id="aff3"><label>c</label>School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama;</aff><aff id="aff4"><label>d</label>Section of Neonatology, Department of Surgical and Medical Critical Care, Careggi University Hospital of Florence, Florence, Italy;</aff><aff id="aff5"><label>e</label>Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, United Kingdom;</aff><aff id="aff6"><label>f</label>Department of Health Science, University of Leicester, Leicester, United Kingdom;</aff><aff id="aff7"><label>g</label>Neonatology, Maternite Regionale Universitaire, Nancy, France;</aff><aff id="aff8"><label>h</label>Department of Pediatrics, Case Western Reserve University and Rainbow Babies & Children's Hospital, Cleveland, Ohio;</aff><aff id="aff9"><label>i</label>Department of Pediatrics, University of Colorado School of Medicine, Denver, Colorado;</aff><aff id="aff10"><label>j</label>Department of Pediatric Emergency Medicine, Hôpital Robert Debré, Université Paris-7 Denis Diderot, Paris, France;</aff><aff id="aff11"><label>k</label>Division of Neonatology, University of California, San Diego, California;</aff><aff id="aff12"><label>l</label>Department of Pediatrics, University of Chicago, Chicago, Illinois;</aff><aff id="aff13"><label>m</label>Division of Neonatology, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand;</aff><aff id="aff14"><label>n</label>Neonatal Unit, Liverpool Women's Hospital, Liverpool, United Kingdom;</aff><aff id="aff15"><label>o</label>Division of Neonatal and Developmental Medicine, Stanford University School of Medicine and Lucile Salter Packard Children's Hospital, Palo Alto, California;</aff><aff id="aff16"><label>p</label>Division of Neonatology, Centre Hospitalier Universitaire Ste-Justine, Montreal, Quebec, Canada; and</aff><aff id="aff17"><label>q</label>Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut</aff></contrib-group><author-notes><corresp>Address correspondence to Lisa M. Askie, PhD, MPH, NHMRC Clinical Trials Centre, University of Sydney, Locked Bag 77, Camperdown, New South Wales 1450, Australia. E-mail: <email>laskie@ctc.usyd.edu.au</email></corresp></author-notes><pub-date pub-type="ppub"><month>10</month><year>2011</year></pub-date><pub-date pub-type="pmc-release"><day>1</day><month>10</month><year>2012</year></pub-date><pmc-comment> PMC Release delay is 12 months and 0 days and was based on the
<volume>128</volume><issue>4</issue><fpage>729</fpage><lpage>739</lpage><history><date date-type="accepted"><day>9</day><month>6</month><year>2011</year></date></history><permissions><copyright-statement>Copyright © 2011 by the American Academy of Pediatrics</copyright-statement><copyright-year>2011</copyright-year></permissions><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zpe01011000729.pdf"></self-uri><abstract><sec><title>BACKGROUND:</title><p>Inhaled nitric oxide (iNO) is an effective therapy for pulmonary hypertension and hypoxic respiratory failure in term infants. Fourteen randomized controlled trials (<italic>n</italic> = 3430 infants) have been conducted on preterm infants at risk for chronic lung disease (CLD). The study results seem contradictory.</p></sec><sec><title>DESIGN/METHODS:</title><p>Individual-patient data meta-analysis included randomized controlled trials of preterm infants (<37 weeks' gestation). Outcomes were adjusted for trial differences and correlation between siblings.</p></sec><sec><title>RESULTS:</title><p>Data from 3298 infants in 12 trials (96%) were analyzed. There was no statistically significant effect of iNO on death or CLD (59% vs 61%: relative risk [RR]: 0.96 [95% confidence interval (CI): 0.92–1.01]; <italic>P</italic> = .11) or severe neurologic events on imaging (25% vs 23%: RR: 1.12 [95% CI: 0.98–1.28]; <italic>P</italic> = .09). There were no statistically significant differences in iNO effect according to any of the patient-level characteristics tested. In trials that used a starting iNO dose of >5 vs ≤5 ppm there was evidence of improved outcome (interaction <italic>P</italic> = .02); however, these differences were not observed at other levels of exposure to iNO. This result was driven primarily by 1 trial, which also differed according to overall dose, duration, timing, and indication for treatment; a significant reduction in death or CLD (RR: 0.85 [95% CI: 0.74–0.98]) was found.</p></sec><sec><title>CONCLUSIONS:</title><p>Routine use of iNO for treatment of respiratory failure in preterm infants cannot be recommended. The use of a higher starting dose might be associated with improved outcome, but because there were differences in the designs of these trials, it requires further examination.</p></sec></abstract><kwd-group><kwd>inhaled nitric oxide</kwd><kwd>chronic lung disease</kwd><kwd>respiratory disease</kwd><kwd>preterm infants</kwd><kwd>individual-patient data meta-analysis</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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