Assessing the neuroprotective benefits for babies of antenatal magnesium sulphate: An individual participant data meta-analysis
Identifieur interne : 002757 ( Pmc/Curation ); précédent : 002756; suivant : 002758Assessing the neuroprotective benefits for babies of antenatal magnesium sulphate: An individual participant data meta-analysis
Auteurs : Caroline A. Crowther [Nouvelle-Zélande, Australie] ; Philippa F. Middleton [Australie] ; Merryn Voysey [Royaume-Uni] ; Lisa Askie [Australie] ; Lelia Duley [Royaume-Uni] ; Peter G. Pryde [États-Unis] ; Stéphane Marret [France] ; Lex W. Doyle [Australie]Source :
- PLoS Medicine [ 1549-1277 ] ; 2017.
Abstract
Babies born preterm are at an increased risk of dying in the first weeks of life, and those who survive have a higher rate of cerebral palsy (CP) compared with babies born at term. The aim of this individual participant data (IPD) meta-analysis (MA) was to assess the effects of antenatal magnesium sulphate, compared with no magnesium treatment, given to women at risk of preterm birth on important maternal and fetal outcomes, including survival free of CP, and whether effects differed by participant or treatment characteristics such as the reason the woman was at risk of preterm birth, why treatment was given, the gestational age at which magnesium sulphate treatment was received, or the dose and timing of the administration of magnesium sulphate.
Trials in which women considered at risk of preterm birth (<37 weeks’ gestation) were randomised to magnesium sulphate or control treatment and where neurologic outcomes for the baby were reported were eligible for inclusion. The primary outcomes were infant death or CP and severe maternal outcome potentially related to treatment. Studies were identified based on the Cochrane Pregnancy and Childbirth search strategy using the terms [antenatal or prenatal] and [magnesium] and [preterm or premature or neuroprotection or 'cerebral palsy']. The date of the last search was 28 February 2017. IPD were sought from investigators with eligible trials. Risk of bias was assessed using criteria from the Cochrane Collaboration. For each prespecified outcome, IPD were analysed using a 1-stage approach. All 5 trials identified were included, with 5,493 women and 6,131 babies. Overall, there was no clear effect of magnesium sulphate treatment compared with no treatment on the primary infant composite outcome of death or CP (relative risk [RR] 0.94, 95% confidence interval (CI) 0.85 to 1.05, 6,131 babies, 5 trials,
Antenatal magnesium sulphate given prior to preterm birth for fetal neuroprotection prevents CP and reduces the combined risk of fetal/infant death or CP. Benefit is seen regardless of the reason for preterm birth, with similar effects across a range of preterm gestational ages and different treatment regimens. Widespread adoption worldwide of this relatively inexpensive, easy-to-administer treatment would lead to important global health benefits for infants born preterm.
Url:
DOI: 10.1371/journal.pmed.1002398
PubMed: 28976987
PubMed Central: 5627896
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Doyle</name><affiliation wicri:level="1"><nlm:aff id="aff010"><addr-line>Department of Obstetrics and Gynaecology, The Royal Women’s’ Hospital, University of Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Obstetrics and Gynaecology, The Royal Women’s’ Hospital, University of Melbourne</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff011"><addr-line>Clinical Sciences, Murdoch Children’s Research Institute, Parkville, Victoria, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Clinical Sciences, Murdoch Children’s Research Institute, Parkville, Victoria</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff012"><addr-line>Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Paediatrics, University of Melbourne, Parkville, Victoria</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">28976987</idno><idno type="pmc">5627896</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5627896</idno><idno type="RBID">PMC:5627896</idno><idno type="doi">10.1371/journal.pmed.1002398</idno><date when="2017">2017</date><idno type="wicri:Area/Pmc/Corpus">002907</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002907</idno><idno type="wicri:Area/Pmc/Curation">002757</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">002757</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Assessing the neuroprotective benefits for babies of antenatal magnesium sulphate: An individual participant data meta-analysis</title><author><name sortKey="Crowther, Caroline A" sort="Crowther, Caroline A" uniqKey="Crowther C" first="Caroline A." last="Crowther">Caroline A. Crowther</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Liggins Institute, University of Auckland, Auckland, New Zealand</addr-line></nlm:aff><country xml:lang="fr">Nouvelle-Zélande</country><wicri:regionArea>Liggins Institute, University of Auckland, Auckland</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff002"><addr-line>Australian Research Centre for Health of Women and Babies (ARCH), The Robinson Research Institute, Discipline of Obstetrics and Gynaecology, School of Medicine, The University of Adelaide, Adelaide, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Australian Research Centre for Health of Women and Babies (ARCH), The Robinson Research Institute, Discipline of Obstetrics and Gynaecology, School of Medicine, The University of Adelaide, Adelaide</wicri:regionArea></affiliation></author><author><name sortKey="Middleton, Philippa F" sort="Middleton, Philippa F" uniqKey="Middleton P" first="Philippa F." last="Middleton">Philippa F. Middleton</name><affiliation wicri:level="1"><nlm:aff id="aff002"><addr-line>Australian Research Centre for Health of Women and Babies (ARCH), The Robinson Research Institute, Discipline of Obstetrics and Gynaecology, School of Medicine, The University of Adelaide, Adelaide, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Australian Research Centre for Health of Women and Babies (ARCH), The Robinson Research Institute, Discipline of Obstetrics and Gynaecology, School of Medicine, The University of Adelaide, Adelaide</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff003"><addr-line>Healthy Mothers Babies and Children, South Australian, Health and Medical Research Institute, Adelaide, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Healthy Mothers Babies and Children, South Australian, Health and Medical Research Institute, Adelaide</wicri:regionArea></affiliation></author><author><name sortKey="Voysey, Merryn" sort="Voysey, Merryn" uniqKey="Voysey M" first="Merryn" last="Voysey">Merryn Voysey</name><affiliation wicri:level="1"><nlm:aff id="aff004"><addr-line>Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford</wicri:regionArea></affiliation></author><author><name sortKey="Askie, Lisa" sort="Askie, Lisa" uniqKey="Askie L" first="Lisa" last="Askie">Lisa Askie</name><affiliation wicri:level="1"><nlm:aff id="aff005"><addr-line>NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>NHMRC Clinical Trials Centre, University of Sydney, Sydney</wicri:regionArea></affiliation></author><author><name sortKey="Duley, Lelia" sort="Duley, Lelia" uniqKey="Duley L" first="Lelia" last="Duley">Lelia Duley</name><affiliation wicri:level="1"><nlm:aff id="aff006"><addr-line>Nottingham Clinical Trials Unit, Nottingham Health Science Partners, Queens Medical Centre, Nottingham, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Nottingham Clinical Trials Unit, Nottingham Health Science Partners, Queens Medical Centre, Nottingham</wicri:regionArea></affiliation></author><author><name sortKey="Pryde, Peter G" sort="Pryde, Peter G" uniqKey="Pryde P" first="Peter G." last="Pryde">Peter G. Pryde</name><affiliation wicri:level="1"><nlm:aff id="aff007"><addr-line>The University of Wisconsin Medical School, Madison, Wisconsin, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>The University of Wisconsin Medical School, Madison, Wisconsin</wicri:regionArea></affiliation></author><author><name sortKey="Marret, Stephane" sort="Marret, Stephane" uniqKey="Marret S" first="Stéphane" last="Marret">Stéphane Marret</name><affiliation wicri:level="1"><nlm:aff id="aff008"><addr-line>Department of Neonatal Medicine and Neuropediatrics, Rouen University Hospital, Rouen, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Department of Neonatal Medicine and Neuropediatrics, Rouen University Hospital, Rouen</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff009"><addr-line>INSERM U 1245, Neovasc team, Perinatal neurological handicap and Neuroprotection IRIB, School of Medicine, Normandy University, Rouen, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM U 1245, Neovasc team, Perinatal neurological handicap and Neuroprotection IRIB, School of Medicine, Normandy University, Rouen</wicri:regionArea></affiliation></author><author><name sortKey="Doyle, Lex W" sort="Doyle, Lex W" uniqKey="Doyle L" first="Lex W." last="Doyle">Lex W. Doyle</name><affiliation wicri:level="1"><nlm:aff id="aff010"><addr-line>Department of Obstetrics and Gynaecology, The Royal Women’s’ Hospital, University of Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Obstetrics and Gynaecology, The Royal Women’s’ Hospital, University of Melbourne</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff011"><addr-line>Clinical Sciences, Murdoch Children’s Research Institute, Parkville, Victoria, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Clinical Sciences, Murdoch Children’s Research Institute, Parkville, Victoria</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff012"><addr-line>Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Paediatrics, University of Melbourne, Parkville, Victoria</wicri:regionArea></affiliation></author></analytic><series><title level="j">PLoS Medicine</title><idno type="ISSN">1549-1277</idno><idno type="eISSN">1549-1676</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="sec001"><title>Background</title><p>Babies born preterm are at an increased risk of dying in the first weeks of life, and those who survive have a higher rate of cerebral palsy (CP) compared with babies born at term. The aim of this individual participant data (IPD) meta-analysis (MA) was to assess the effects of antenatal magnesium sulphate, compared with no magnesium treatment, given to women at risk of preterm birth on important maternal and fetal outcomes, including survival free of CP, and whether effects differed by participant or treatment characteristics such as the reason the woman was at risk of preterm birth, why treatment was given, the gestational age at which magnesium sulphate treatment was received, or the dose and timing of the administration of magnesium sulphate.</p></sec><sec id="sec002"><title>Methods and findings</title><p>Trials in which women considered at risk of preterm birth (<37 weeks’ gestation) were randomised to magnesium sulphate or control treatment and where neurologic outcomes for the baby were reported were eligible for inclusion. The primary outcomes were infant death or CP and severe maternal outcome potentially related to treatment. Studies were identified based on the Cochrane Pregnancy and Childbirth search strategy using the terms [antenatal or prenatal] and [magnesium] and [preterm or premature or neuroprotection or 'cerebral palsy']. The date of the last search was 28 February 2017. IPD were sought from investigators with eligible trials. Risk of bias was assessed using criteria from the Cochrane Collaboration. For each prespecified outcome, IPD were analysed using a 1-stage approach. All 5 trials identified were included, with 5,493 women and 6,131 babies. Overall, there was no clear effect of magnesium sulphate treatment compared with no treatment on the primary infant composite outcome of death or CP (relative risk [RR] 0.94, 95% confidence interval (CI) 0.85 to 1.05, 6,131 babies, 5 trials, <italic>p</italic> = 0.07 for heterogeneity of treatment effect across trials). In the prespecified sensitivity analysis restricted to data from the 4 trials in which the intent of treatment was fetal neuroprotection, there was a significant reduction in the risk of death or CP with magnesium sulphate treatment compared with no treatment (RR 0.86, 95% CI 0.75 to 0.99, 4,448 babies, 4 trials), with no significant heterogeneity (<italic>p</italic> = 0.28). The number needed to treat (NNT) to benefit was 41 women/babies to prevent 1 baby from either dying or having CP. For the primary outcome of severe maternal outcome potentially related to magnesium sulphate treatment, no events were recorded from the 2 trials providing data. When the individual components of the composite infant outcome were assessed, no effect was seen for death overall (RR 1.03, 95% CI 0.91 to 1.17, 6,131 babies, 5 trials) or in the analysis of death using only data from trials with the intent of fetal neuroprotection (RR 0.95, 95% CI 0.80 to 1.13, 4,448 babies, 4 trials). For cerebral palsy in survivors, magnesium sulphate treatment had a strong protective effect in both the overall analysis (RR 0.68, 95% CI 0.54 to 0.87, 4,601 babies, 5 trials, NNT to benefit 46) and the neuroprotective intent analysis (RR 0.68, 95% CI 0.53 to 0.87, 3,988 babies, 4 trials, NNT to benefit 42). No statistically significant differences were seen for any of the other secondary outcomes. The treatment effect varied little by the reason the woman was at risk of preterm birth, the gestational age at which magnesium sulphate treatment was given, the total dose received, or whether maintenance therapy was used. A limitation of the study was that not all trials could provide the data required for the planned analyses so that combined with low event rates for some important clinical events, the power to find a difference was limited.</p></sec><sec id="sec003"><title>Conclusions</title><p>Antenatal magnesium sulphate given prior to preterm birth for fetal neuroprotection prevents CP and reduces the combined risk of fetal/infant death or CP. Benefit is seen regardless of the reason for preterm birth, with similar effects across a range of preterm gestational ages and different treatment regimens. Widespread adoption worldwide of this relatively inexpensive, easy-to-administer treatment would lead to important global health benefits for infants born preterm.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Blencowe, H" uniqKey="Blencowe H">H Blencowe</name></author><author><name sortKey="Cousens, S" uniqKey="Cousens S">S Cousens</name></author><author><name sortKey="Oestergaard, Mz" uniqKey="Oestergaard M">MZ Oestergaard</name></author><author><name sortKey="Chou, D" uniqKey="Chou D">D Chou</name></author><author><name sortKey="Moller, Ab" uniqKey="Moller A">AB Moller</name></author><author><name sortKey="Narwal, R" uniqKey="Narwal R">R Narwal</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Saigal, S" uniqKey="Saigal S">S Saigal</name></author><author><name sortKey="Doyle, Lw" uniqKey="Doyle L">LW 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<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS Med</journal-id><journal-id journal-id-type="iso-abbrev">PLoS Med</journal-id><journal-id journal-id-type="publisher-id">plos</journal-id><journal-id journal-id-type="pmc">plosmed</journal-id><journal-title-group><journal-title>PLoS Medicine</journal-title></journal-title-group><issn pub-type="ppub">1549-1277</issn><issn pub-type="epub">1549-1676</issn><publisher><publisher-name>Public Library of Science</publisher-name><publisher-loc>San Francisco, CA USA</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">28976987</article-id><article-id pub-id-type="pmc">5627896</article-id><article-id pub-id-type="doi">10.1371/journal.pmed.1002398</article-id><article-id pub-id-type="publisher-id">PMEDICINE-D-17-01738</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Physical Sciences</subject><subj-group><subject>Chemistry</subject><subj-group><subject>Chemical Elements</subject><subj-group><subject>Magnesium</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Physical Sciences</subject><subj-group><subject>Chemistry</subject><subj-group><subject>Chemical Compounds</subject><subj-group><subject>Salts</subject><subj-group><subject>Sulfates</subject></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Neurology</subject><subj-group><subject>Cerebral Palsy</subject></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Women's Health</subject><subj-group><subject>Maternal Health</subject><subj-group><subject>Birth</subject><subj-group><subject>Preterm Birth</subject></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Women's Health</subject><subj-group><subject>Obstetrics and Gynecology</subject><subj-group><subject>Birth</subject><subj-group><subject>Preterm Birth</subject></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Women's Health</subject><subj-group><subject>Maternal Health</subject><subj-group><subject>Pregnancy</subject><subj-group><subject>Pregnancy Complications</subject><subj-group><subject>Preterm Birth</subject></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Women's Health</subject><subj-group><subject>Obstetrics and Gynecology</subject><subj-group><subject>Pregnancy</subject><subj-group><subject>Pregnancy Complications</subject><subj-group><subject>Preterm Birth</subject></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Women's Health</subject><subj-group><subject>Maternal Health</subject><subj-group><subject>Birth</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Women's Health</subject><subj-group><subject>Obstetrics and Gynecology</subject><subj-group><subject>Birth</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Physical Sciences</subject><subj-group><subject>Materials Science</subject><subj-group><subject>Materials by Attribute</subject><subj-group><subject>Magnets</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Research and Analysis Methods</subject><subj-group><subject>Mathematical and Statistical Techniques</subject><subj-group><subject>Statistical Methods</subject><subj-group><subject>Meta-Analysis</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Physical Sciences</subject><subj-group><subject>Mathematics</subject><subj-group><subject>Statistics (Mathematics)</subject><subj-group><subject>Statistical Methods</subject><subj-group><subject>Meta-Analysis</subject></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Women's Health</subject><subj-group><subject>Maternal Health</subject><subj-group><subject>Pregnancy</subject><subj-group><subject>Pregnancy Complications</subject><subj-group><subject>Fetal Death</subject></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Women's Health</subject><subj-group><subject>Obstetrics and Gynecology</subject><subj-group><subject>Pregnancy</subject><subj-group><subject>Pregnancy Complications</subject><subj-group><subject>Fetal Death</subject></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></article-categories><title-group><article-title>Assessing the neuroprotective benefits for babies of antenatal magnesium sulphate: An individual participant data meta-analysis</article-title><alt-title alt-title-type="running-head">Magnesium sulphate for fetal neuroprotection</alt-title></title-group><contrib-group><contrib contrib-type="author"><contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0002-9079-4451</contrib-id><name><surname>Crowther</surname><given-names>Caroline A.</given-names></name><role content-type="http://credit.casrai.org/">Conceptualization</role><role content-type="http://credit.casrai.org/">Data curation</role><role content-type="http://credit.casrai.org/">Funding acquisition</role><role content-type="http://credit.casrai.org/">Investigation</role><role content-type="http://credit.casrai.org/">Methodology</role><role content-type="http://credit.casrai.org/">Project administration</role><role content-type="http://credit.casrai.org/">Resources</role><role content-type="http://credit.casrai.org/">Supervision</role><role content-type="http://credit.casrai.org/">Validation</role><role content-type="http://credit.casrai.org/">Writing – original draft</role><role content-type="http://credit.casrai.org/">Writing – review & editing</role><xref ref-type="aff" rid="aff001"><sup>1</sup></xref><xref ref-type="aff" rid="aff002"><sup>2</sup></xref><xref ref-type="corresp" rid="cor001">*</xref></contrib><contrib contrib-type="author"><contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0002-8573-338X</contrib-id><name><surname>Middleton</surname><given-names>Philippa F.</given-names></name><role content-type="http://credit.casrai.org/">Conceptualization</role><role content-type="http://credit.casrai.org/">Data curation</role><role content-type="http://credit.casrai.org/">Funding acquisition</role><role content-type="http://credit.casrai.org/">Investigation</role><role content-type="http://credit.casrai.org/">Methodology</role><role content-type="http://credit.casrai.org/">Project administration</role><role content-type="http://credit.casrai.org/">Supervision</role><role content-type="http://credit.casrai.org/">Validation</role><role content-type="http://credit.casrai.org/">Writing – review & editing</role><xref ref-type="aff" rid="aff002"><sup>2</sup></xref><xref ref-type="aff" rid="aff003"><sup>3</sup></xref></contrib><contrib contrib-type="author"><contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0001-6324-6559</contrib-id><name><surname>Voysey</surname><given-names>Merryn</given-names></name><role content-type="http://credit.casrai.org/">Data curation</role><role content-type="http://credit.casrai.org/">Formal analysis</role><role content-type="http://credit.casrai.org/">Investigation</role><role content-type="http://credit.casrai.org/">Methodology</role><role content-type="http://credit.casrai.org/">Software</role><role content-type="http://credit.casrai.org/">Supervision</role><role content-type="http://credit.casrai.org/">Validation</role><role content-type="http://credit.casrai.org/">Writing – review & editing</role><xref ref-type="aff" rid="aff004"><sup>4</sup></xref></contrib><contrib contrib-type="author"><contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0002-8934-5544</contrib-id><name><surname>Askie</surname><given-names>Lisa</given-names></name><role content-type="http://credit.casrai.org/">Conceptualization</role><role content-type="http://credit.casrai.org/">Funding acquisition</role><role content-type="http://credit.casrai.org/">Investigation</role><role content-type="http://credit.casrai.org/">Methodology</role><role content-type="http://credit.casrai.org/">Supervision</role><role content-type="http://credit.casrai.org/">Writing – review & editing</role><xref ref-type="aff" rid="aff005"><sup>5</sup></xref></contrib><contrib contrib-type="author"><name><surname>Duley</surname><given-names>Lelia</given-names></name><role content-type="http://credit.casrai.org/">Funding acquisition</role><role content-type="http://credit.casrai.org/">Investigation</role><role content-type="http://credit.casrai.org/">Validation</role><role content-type="http://credit.casrai.org/">Writing – review & editing</role><xref ref-type="aff" rid="aff006"><sup>6</sup></xref></contrib><contrib contrib-type="author"><contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0001-8279-6943</contrib-id><name><surname>Pryde</surname><given-names>Peter G.</given-names></name><role content-type="http://credit.casrai.org/">Investigation</role><role content-type="http://credit.casrai.org/">Validation</role><role content-type="http://credit.casrai.org/">Writing – review & editing</role><xref ref-type="aff" rid="aff007"><sup>7</sup></xref></contrib><contrib contrib-type="author"><name><surname>Marret</surname><given-names>Stéphane</given-names></name><role content-type="http://credit.casrai.org/">Funding acquisition</role><role content-type="http://credit.casrai.org/">Investigation</role><role content-type="http://credit.casrai.org/">Validation</role><role content-type="http://credit.casrai.org/">Writing – review & editing</role><xref ref-type="aff" rid="aff008"><sup>8</sup></xref><xref ref-type="aff" rid="aff009"><sup>9</sup></xref></contrib><contrib contrib-type="author"><contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0002-7667-7312</contrib-id><name><surname>Doyle</surname><given-names>Lex W.</given-names></name><role content-type="http://credit.casrai.org/">Conceptualization</role><role content-type="http://credit.casrai.org/">Funding acquisition</role><role content-type="http://credit.casrai.org/">Investigation</role><role content-type="http://credit.casrai.org/">Methodology</role><role content-type="http://credit.casrai.org/">Writing – original draft</role><role content-type="http://credit.casrai.org/">Writing – review & editing</role><xref ref-type="aff" rid="aff010"><sup>10</sup></xref><xref ref-type="aff" rid="aff011"><sup>11</sup></xref><xref ref-type="aff" rid="aff012"><sup>12</sup></xref></contrib><contrib contrib-type="author"><collab>for the AMICABLE Group</collab><xref ref-type="author-notes" rid="fn001"><sup>¶</sup></xref></contrib></contrib-group><aff id="aff001"><label>1</label><addr-line>Liggins Institute, University of Auckland, Auckland, New Zealand</addr-line></aff><aff id="aff002"><label>2</label><addr-line>Australian Research Centre for Health of Women and Babies (ARCH), The Robinson Research Institute, Discipline of Obstetrics and Gynaecology, School of Medicine, The University of Adelaide, Adelaide, Australia</addr-line></aff><aff id="aff003"><label>3</label><addr-line>Healthy Mothers Babies and Children, South Australian, Health and Medical Research Institute, Adelaide, Australia</addr-line></aff><aff id="aff004"><label>4</label><addr-line>Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom</addr-line></aff><aff id="aff005"><label>5</label><addr-line>NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia</addr-line></aff><aff id="aff006"><label>6</label><addr-line>Nottingham Clinical Trials Unit, Nottingham Health Science Partners, Queens Medical Centre, Nottingham, United Kingdom</addr-line></aff><aff id="aff007"><label>7</label><addr-line>The University of Wisconsin Medical School, Madison, Wisconsin, United States of America</addr-line></aff><aff id="aff008"><label>8</label><addr-line>Department of Neonatal Medicine and Neuropediatrics, Rouen University Hospital, Rouen, France</addr-line></aff><aff id="aff009"><label>9</label><addr-line>INSERM U 1245, Neovasc team, Perinatal neurological handicap and Neuroprotection IRIB, School of Medicine, Normandy University, Rouen, France</addr-line></aff><aff id="aff010"><label>10</label><addr-line>Department of Obstetrics and Gynaecology, The Royal Women’s’ Hospital, University of Melbourne, Australia</addr-line></aff><aff id="aff011"><label>11</label><addr-line>Clinical Sciences, Murdoch Children’s Research Institute, Parkville, Victoria, Australia</addr-line></aff><aff id="aff012"><label>12</label><addr-line>Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia</addr-line></aff><contrib-group><contrib contrib-type="editor"><name><surname>Myers</surname><given-names>Jenny E</given-names></name><role>Academic Editor</role><xref ref-type="aff" rid="edit1"></xref></contrib></contrib-group><aff id="edit1"><addr-line>University of Manchester, UNITED KINGDOM</addr-line></aff><author-notes><fn fn-type="COI-statement" id="coi001"><p>The authors have declared that no competing interests exist.</p></fn><fn fn-type="other" id="fn001"><p>¶ Membership of the AMICABLE Group is provided in the Acknowledgements.</p></fn><corresp id="cor001">* E-mail: <email>c.crowther@auckland.ac.nz</email></corresp></author-notes><pub-date pub-type="epub"><day>4</day><month>10</month><year>2017</year></pub-date><pub-date pub-type="collection"><month>10</month><year>2017</year></pub-date><volume>14</volume><issue>10</issue><elocation-id>e1002398</elocation-id><history><date date-type="received"><day>23</day><month>5</month><year>2017</year></date><date date-type="accepted"><day>31</day><month>8</month><year>2017</year></date></history><permissions><copyright-statement>© 2017 Crowther et al</copyright-statement><copyright-year>2017</copyright-year><copyright-holder>Crowther et al</copyright-holder><license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</ext-link>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p></license></permissions><self-uri content-type="pdf" xlink:href="pmed.1002398.pdf"></self-uri><abstract><sec id="sec001"><title>Background</title><p>Babies born preterm are at an increased risk of dying in the first weeks of life, and those who survive have a higher rate of cerebral palsy (CP) compared with babies born at term. The aim of this individual participant data (IPD) meta-analysis (MA) was to assess the effects of antenatal magnesium sulphate, compared with no magnesium treatment, given to women at risk of preterm birth on important maternal and fetal outcomes, including survival free of CP, and whether effects differed by participant or treatment characteristics such as the reason the woman was at risk of preterm birth, why treatment was given, the gestational age at which magnesium sulphate treatment was received, or the dose and timing of the administration of magnesium sulphate.</p></sec><sec id="sec002"><title>Methods and findings</title><p>Trials in which women considered at risk of preterm birth (<37 weeks’ gestation) were randomised to magnesium sulphate or control treatment and where neurologic outcomes for the baby were reported were eligible for inclusion. The primary outcomes were infant death or CP and severe maternal outcome potentially related to treatment. Studies were identified based on the Cochrane Pregnancy and Childbirth search strategy using the terms [antenatal or prenatal] and [magnesium] and [preterm or premature or neuroprotection or 'cerebral palsy']. The date of the last search was 28 February 2017. IPD were sought from investigators with eligible trials. Risk of bias was assessed using criteria from the Cochrane Collaboration. For each prespecified outcome, IPD were analysed using a 1-stage approach. All 5 trials identified were included, with 5,493 women and 6,131 babies. Overall, there was no clear effect of magnesium sulphate treatment compared with no treatment on the primary infant composite outcome of death or CP (relative risk [RR] 0.94, 95% confidence interval (CI) 0.85 to 1.05, 6,131 babies, 5 trials, <italic>p</italic> = 0.07 for heterogeneity of treatment effect across trials). In the prespecified sensitivity analysis restricted to data from the 4 trials in which the intent of treatment was fetal neuroprotection, there was a significant reduction in the risk of death or CP with magnesium sulphate treatment compared with no treatment (RR 0.86, 95% CI 0.75 to 0.99, 4,448 babies, 4 trials), with no significant heterogeneity (<italic>p</italic> = 0.28). The number needed to treat (NNT) to benefit was 41 women/babies to prevent 1 baby from either dying or having CP. For the primary outcome of severe maternal outcome potentially related to magnesium sulphate treatment, no events were recorded from the 2 trials providing data. When the individual components of the composite infant outcome were assessed, no effect was seen for death overall (RR 1.03, 95% CI 0.91 to 1.17, 6,131 babies, 5 trials) or in the analysis of death using only data from trials with the intent of fetal neuroprotection (RR 0.95, 95% CI 0.80 to 1.13, 4,448 babies, 4 trials). For cerebral palsy in survivors, magnesium sulphate treatment had a strong protective effect in both the overall analysis (RR 0.68, 95% CI 0.54 to 0.87, 4,601 babies, 5 trials, NNT to benefit 46) and the neuroprotective intent analysis (RR 0.68, 95% CI 0.53 to 0.87, 3,988 babies, 4 trials, NNT to benefit 42). No statistically significant differences were seen for any of the other secondary outcomes. The treatment effect varied little by the reason the woman was at risk of preterm birth, the gestational age at which magnesium sulphate treatment was given, the total dose received, or whether maintenance therapy was used. A limitation of the study was that not all trials could provide the data required for the planned analyses so that combined with low event rates for some important clinical events, the power to find a difference was limited.</p></sec><sec id="sec003"><title>Conclusions</title><p>Antenatal magnesium sulphate given prior to preterm birth for fetal neuroprotection prevents CP and reduces the combined risk of fetal/infant death or CP. Benefit is seen regardless of the reason for preterm birth, with similar effects across a range of preterm gestational ages and different treatment regimens. Widespread adoption worldwide of this relatively inexpensive, easy-to-administer treatment would lead to important global health benefits for infants born preterm.</p></sec></abstract><abstract abstract-type="toc"><p>In an individual participant data meta-analysis, Caroline Crowther and colleagues examine the evidence for the neuroprotective benefits of antenatal magnesium sulphate for babies.</p></abstract><abstract abstract-type="summary"><title>Author summary</title><sec id="sec004"><title>Why was the study done?</title><list list-type="bullet"><list-item><p>Effective therapies that can reduce the risk of neurological impairments and disabilities from preterm birth are needed.</p></list-item><list-item><p>Antenatal magnesium sulphate given to women at imminent risk of preterm birth reduces the risk of cerebral palsy in their babies in aggregate data meta-analysis.</p></list-item><list-item><p>The aims of the AMICABLE (<underline>A</underline>ntenatal <underline>m</underline>agnesium sulphate <underline>i</underline>ndividual participant data international <underline>c</underline>ollaboration: <underline>A</underline>ssessing the benefits for babies using the <underline>b</underline>est <underline>l</underline>evel of <underline>e</underline>vidence) individual participant data meta-analysis (IPD-MA) were to assess the effect of antenatal magnesium sulphate when given to women at risk of preterm birth on important clinical outcomes and whether treatment effects varied depending on participant and treatment factors.</p></list-item></list></sec><sec id="sec005"><title>What did the researchers do and find?</title><list list-type="bullet"><list-item><p>Five randomised trials with 5,493 women and 6,131 babies were identified as including women at risk of preterm birth who were allocated magnesium sulphate or control treatment and in which neurologic outcomes for the baby were reported and included.</p></list-item><list-item><p>Antenatal magnesium sulphate given to women at imminent risk of preterm birth for fetal neuroprotection prevents cerebral palsy and reduces the combined risk of fetal/infant death or cerebral palsy.</p></list-item><list-item><p>Benefit was seen regardless of the reason for preterm birth, across a range of preterm gestational ages, and with minimal variation in outcomes related to time prior to birth or dosage given.</p></list-item></list></sec><sec id="sec006"><title>What do these findings mean?</title><list list-type="bullet"><list-item><p>Antenatal magnesium sulphate for fetal neuroprotection can be recommended to be given close to planned or expected preterm birth using the smallest effective dose of 4 g with or without a 1 g/hour maintenance dose.</p></list-item><list-item><p>Antenatal magnesium sulphate is an inexpensive, effective treatment that can reduce the burden of death and cerebral palsy in babies born very preterm.</p></list-item><list-item><p>Widespread adoption of recommendations to use antenatal magnesium sulphate prior to preterm birth could lead to significant global health benefits.</p></list-item></list></sec></abstract><funding-group><award-group id="award001"><funding-source><institution-wrap><institution-id institution-id-type="funder-id">http://dx.doi.org/10.13039/501100000925</institution-id><institution>National Health and Medical Research Council</institution></institution-wrap></funding-source><award-id>627228</award-id><principal-award-recipient><contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0002-9079-4451</contrib-id><name><surname>Crowther</surname><given-names>Caroline A.</given-names></name></principal-award-recipient></award-group><award-group id="award002"><funding-source><institution>National Health and Medical Research Council (AU)</institution></funding-source><award-id>1060733</award-id></award-group><funding-statement>The AMICABLE IPD Study was funded by a Project Grant (ID 627228) from the Australian National Health and Medical Research Council (NHMRC) and indirectly through a Centre for Research Excellence NHMRC grant (ID 1060733). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</funding-statement></funding-group><counts><fig-count count="1"></fig-count><table-count count="17"></table-count><page-count count="24"></page-count></counts><custom-meta-group><custom-meta id="data-availability"><meta-name>Data Availability</meta-name><meta-value>The datasets included in this IPD-MA are available upon request. Contact information for each trial is provided in S1 Table.</meta-value></custom-meta></custom-meta-group></article-meta><notes><title>Data Availability</title><p>The datasets included in this IPD-MA are available upon request. Contact information for each trial is provided in S1 Table.</p></notes></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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