Assessing the neuroprotective benefits for babies of antenatal magnesium sulphate: An individual participant data meta-analysis.
Identifieur interne : 001174 ( PubMed/Checkpoint ); précédent : 001173; suivant : 001175Assessing the neuroprotective benefits for babies of antenatal magnesium sulphate: An individual participant data meta-analysis.
Auteurs : Caroline A. Crowther [Nouvelle-Zélande] ; 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 [ 1549-1676 ] ; 2017.
Descripteurs français
- KwdFr :
- Délai jusqu'au traitement (), Essais contrôlés randomisés comme sujet, Femelle, Grossesse, Humains, Mortalité infantile, Naissance prématurée (), Naissance prématurée (mortalité), Naissance prématurée (physiopathologie), Naissance prématurée (sang), Neuroprotecteurs (administration et posologie), Neuroprotecteurs (sang), Nourrisson, Nouveau-né, Paralysie cérébrale (), Paralysie cérébrale (sang), Paralysie cérébrale (épidémiologie), Paralysie cérébrale (étiologie), Prise en charge prénatale (), Prématuré (sang), Relation dose-effet des médicaments, Sang foetal (), Sulfate de magnésium (administration et posologie), Sulfate de magnésium (sang), Âge gestationnel, Évaluation des résultats et des processus en soins de santé.
- MESH :
- administration et posologie : Neuroprotecteurs, Sulfate de magnésium.
- mortalité : Naissance prématurée.
- physiopathologie : Naissance prématurée.
- sang : Naissance prématurée, Neuroprotecteurs, Paralysie cérébrale, Prématuré, Sulfate de magnésium.
- épidémiologie : Paralysie cérébrale.
- étiologie : Paralysie cérébrale.
- Délai jusqu'au traitement, Essais contrôlés randomisés comme sujet, Femelle, Grossesse, Humains, Mortalité infantile, Naissance prématurée, Nourrisson, Nouveau-né, Paralysie cérébrale, Prise en charge prénatale, Relation dose-effet des médicaments, Sang foetal, Âge gestationnel, Évaluation des résultats et des processus en soins de santé.
English descriptors
- KwdEn :
- Cerebral Palsy (blood), Cerebral Palsy (epidemiology), Cerebral Palsy (etiology), Cerebral Palsy (prevention & control), Dose-Response Relationship, Drug, Female, Fetal Blood (chemistry), Gestational Age, Humans, Infant, Infant Mortality, Infant, Newborn, Infant, Premature (blood), Magnesium Sulfate (administration & dosage), Magnesium Sulfate (blood), Neuroprotective Agents (administration & dosage), Neuroprotective Agents (blood), Outcome and Process Assessment (Health Care), Pregnancy, Premature Birth (blood), Premature Birth (mortality), Premature Birth (physiopathology), Premature Birth (therapy), Prenatal Care (methods), Randomized Controlled Trials as Topic, Time-to-Treatment (statistics & numerical data).
- MESH :
- chemical , administration & dosage : Magnesium Sulfate, Neuroprotective Agents.
- blood : Cerebral Palsy, Infant, Premature, Magnesium Sulfate, Neuroprotective Agents, Premature Birth.
- chemistry : Fetal Blood.
- epidemiology : Cerebral Palsy.
- etiology : Cerebral Palsy.
- methods : Prenatal Care.
- mortality : Premature Birth.
- physiopathology : Premature Birth.
- prevention & control : Cerebral Palsy.
- statistics & numerical data : Time-to-Treatment.
- therapy : Premature Birth.
- Dose-Response Relationship, Drug, Female, Gestational Age, Humans, Infant, Infant Mortality, Infant, Newborn, Outcome and Process Assessment (Health Care), Pregnancy, Randomized Controlled Trials as Topic.
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.
DOI: 10.1371/journal.pmed.1002398
PubMed: 28976987
Affiliations:
- Australie, France, Nouvelle-Zélande, Royaume-Uni, États-Unis
- Angleterre, Haute-Normandie, Nouvelle-Galles du Sud, Oxfordshire, Région Normandie, Victoria (État), Wisconsin
- Melbourne, Oxford, Rouen, Sydney
- Université d'Oxford, Université de Melbourne, Université de Sydney
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pubmed:28976987Le document en format XML
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Cerebral Palsy (blood)</term>
<term>Cerebral Palsy (epidemiology)</term>
<term>Cerebral Palsy (etiology)</term>
<term>Cerebral Palsy (prevention & control)</term>
<term>Dose-Response Relationship, Drug</term>
<term>Female</term>
<term>Fetal Blood (chemistry)</term>
<term>Gestational Age</term>
<term>Humans</term>
<term>Infant</term>
<term>Infant Mortality</term>
<term>Infant, Newborn</term>
<term>Infant, Premature (blood)</term>
<term>Magnesium Sulfate (administration & dosage)</term>
<term>Magnesium Sulfate (blood)</term>
<term>Neuroprotective Agents (administration & dosage)</term>
<term>Neuroprotective Agents (blood)</term>
<term>Outcome and Process Assessment (Health Care)</term>
<term>Pregnancy</term>
<term>Premature Birth (blood)</term>
<term>Premature Birth (mortality)</term>
<term>Premature Birth (physiopathology)</term>
<term>Premature Birth (therapy)</term>
<term>Prenatal Care (methods)</term>
<term>Randomized Controlled Trials as Topic</term>
<term>Time-to-Treatment (statistics & numerical data)</term>
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<term>Essais contrôlés randomisés comme sujet</term>
<term>Femelle</term>
<term>Grossesse</term>
<term>Humains</term>
<term>Mortalité infantile</term>
<term>Naissance prématurée ()</term>
<term>Naissance prématurée (mortalité)</term>
<term>Naissance prématurée (physiopathologie)</term>
<term>Naissance prématurée (sang)</term>
<term>Neuroprotecteurs (administration et posologie)</term>
<term>Neuroprotecteurs (sang)</term>
<term>Nourrisson</term>
<term>Nouveau-né</term>
<term>Paralysie cérébrale ()</term>
<term>Paralysie cérébrale (sang)</term>
<term>Paralysie cérébrale (épidémiologie)</term>
<term>Paralysie cérébrale (étiologie)</term>
<term>Prise en charge prénatale ()</term>
<term>Prématuré (sang)</term>
<term>Relation dose-effet des médicaments</term>
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<term>Sulfate de magnésium (administration et posologie)</term>
<term>Sulfate de magnésium (sang)</term>
<term>Âge gestationnel</term>
<term>Évaluation des résultats et des processus en soins de santé</term>
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<term>Neuroprotective Agents</term>
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<term>Sulfate de magnésium</term>
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<term>Infant, Premature</term>
<term>Magnesium Sulfate</term>
<term>Neuroprotective Agents</term>
<term>Premature Birth</term>
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<keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>Naissance prématurée</term>
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<term>Paralysie cérébrale</term>
<term>Prématuré</term>
<term>Sulfate de magnésium</term>
</keywords>
<keywords scheme="MESH" qualifier="statistics & numerical data" xml:lang="en"><term>Time-to-Treatment</term>
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<keywords scheme="MESH" qualifier="therapy" xml:lang="en"><term>Premature Birth</term>
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<term>Humans</term>
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<term>Infant Mortality</term>
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<term>Outcome and Process Assessment (Health Care)</term>
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<term>Randomized Controlled Trials as Topic</term>
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<term>Essais contrôlés randomisés comme sujet</term>
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<term>Prise en charge prénatale</term>
<term>Relation dose-effet des médicaments</term>
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<front><div type="abstract" xml:lang="en">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.</div>
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<ELocationID EIdType="doi" ValidYN="Y">10.1371/journal.pmed.1002398</ELocationID>
<Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">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.</AbstractText>
<AbstractText Label="METHODS AND FINDINGS" NlmCategory="RESULTS">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, p = 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 (p = 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.</AbstractText>
<AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">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.</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Crowther</LastName>
<ForeName>Caroline A</ForeName>
<Initials>CA</Initials>
<Identifier Source="ORCID">http://orcid.org/0000-0002-9079-4451</Identifier>
<AffiliationInfo><Affiliation>Liggins Institute, University of Auckland, Auckland, New Zealand.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>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.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Middleton</LastName>
<ForeName>Philippa F</ForeName>
<Initials>PF</Initials>
<Identifier Source="ORCID">http://orcid.org/0000-0002-8573-338X</Identifier>
<AffiliationInfo><Affiliation>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.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Healthy Mothers Babies and Children, South Australian, Health and Medical Research Institute, Adelaide, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Voysey</LastName>
<ForeName>Merryn</ForeName>
<Initials>M</Initials>
<Identifier Source="ORCID">http://orcid.org/0000-0001-6324-6559</Identifier>
<AffiliationInfo><Affiliation>Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Askie</LastName>
<ForeName>Lisa</ForeName>
<Initials>L</Initials>
<Identifier Source="ORCID">http://orcid.org/0000-0002-8934-5544</Identifier>
<AffiliationInfo><Affiliation>NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Duley</LastName>
<ForeName>Lelia</ForeName>
<Initials>L</Initials>
<AffiliationInfo><Affiliation>Nottingham Clinical Trials Unit, Nottingham Health Science Partners, Queens Medical Centre, Nottingham, United Kingdom.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Pryde</LastName>
<ForeName>Peter G</ForeName>
<Initials>PG</Initials>
<Identifier Source="ORCID">http://orcid.org/0000-0001-8279-6943</Identifier>
<AffiliationInfo><Affiliation>The University of Wisconsin Medical School, Madison, Wisconsin, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Marret</LastName>
<ForeName>Stéphane</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Department of Neonatal Medicine and Neuropediatrics, Rouen University Hospital, Rouen, France.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>INSERM U 1245, Neovasc team, Perinatal neurological handicap and Neuroprotection IRIB, School of Medicine, Normandy University, Rouen, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Doyle</LastName>
<ForeName>Lex W</ForeName>
<Initials>LW</Initials>
<Identifier Source="ORCID">http://orcid.org/0000-0002-7667-7312</Identifier>
<AffiliationInfo><Affiliation>Department of Obstetrics and Gynaecology, The Royal Women's' Hospital, University of Melbourne, Australia.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Clinical Sciences, Murdoch Children's Research Institute, Parkville, Victoria, Australia.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><CollectiveName>AMICABLE Group</CollectiveName>
</Author>
</AuthorList>
<Language>eng</Language>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
<PublicationType UI="D017418">Meta-Analysis</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2017</Year>
<Month>10</Month>
<Day>04</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>United States</Country>
<MedlineTA>PLoS Med</MedlineTA>
<NlmUniqueID>101231360</NlmUniqueID>
<ISSNLinking>1549-1277</ISSNLinking>
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<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D018696">Neuroprotective Agents</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>7487-88-9</RegistryNumber>
<NameOfSubstance UI="D008278">Magnesium Sulfate</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
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<MeshHeadingList><MeshHeading><DescriptorName UI="D002547" MajorTopicYN="Y">Cerebral Palsy</DescriptorName>
<QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName>
<QualifierName UI="Q000453" MajorTopicYN="N">epidemiology</QualifierName>
<QualifierName UI="Q000209" MajorTopicYN="N">etiology</QualifierName>
<QualifierName UI="Q000517" MajorTopicYN="N">prevention & control</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D004305" MajorTopicYN="N">Dose-Response Relationship, Drug</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D005312" MajorTopicYN="N">Fetal Blood</DescriptorName>
<QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D005865" MajorTopicYN="N">Gestational Age</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D007223" MajorTopicYN="N">Infant</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D007226" MajorTopicYN="N">Infant Mortality</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D007231" MajorTopicYN="N">Infant, Newborn</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D007234" MajorTopicYN="N">Infant, Premature</DescriptorName>
<QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008278" MajorTopicYN="Y">Magnesium Sulfate</DescriptorName>
<QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName>
<QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D018696" MajorTopicYN="N">Neuroprotective Agents</DescriptorName>
<QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName>
<QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D010043" MajorTopicYN="N">Outcome and Process Assessment (Health Care)</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D011247" MajorTopicYN="N">Pregnancy</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D047928" MajorTopicYN="Y">Premature Birth</DescriptorName>
<QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName>
<QualifierName UI="Q000401" MajorTopicYN="N">mortality</QualifierName>
<QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName>
<QualifierName UI="Q000628" MajorTopicYN="N">therapy</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D011295" MajorTopicYN="N">Prenatal Care</DescriptorName>
<QualifierName UI="Q000379" MajorTopicYN="N">methods</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D016032" MajorTopicYN="N">Randomized Controlled Trials as Topic</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D061665" MajorTopicYN="N">Time-to-Treatment</DescriptorName>
<QualifierName UI="Q000706" MajorTopicYN="N">statistics & numerical data</QualifierName>
</MeshHeading>
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<Month>05</Month>
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<affiliations><list><country><li>Australie</li>
<li>France</li>
<li>Nouvelle-Zélande</li>
<li>Royaume-Uni</li>
<li>États-Unis</li>
</country>
<region><li>Angleterre</li>
<li>Haute-Normandie</li>
<li>Nouvelle-Galles du Sud</li>
<li>Oxfordshire</li>
<li>Région Normandie</li>
<li>Victoria (État)</li>
<li>Wisconsin</li>
</region>
<settlement><li>Melbourne</li>
<li>Oxford</li>
<li>Rouen</li>
<li>Sydney</li>
</settlement>
<orgName><li>Université d'Oxford</li>
<li>Université de Melbourne</li>
<li>Université de Sydney</li>
</orgName>
</list>
<tree><country name="Nouvelle-Zélande"><noRegion><name sortKey="Crowther, Caroline A" sort="Crowther, Caroline A" uniqKey="Crowther C" first="Caroline A" last="Crowther">Caroline A. Crowther</name>
</noRegion>
</country>
<country name="Australie"><noRegion><name sortKey="Middleton, Philippa F" sort="Middleton, Philippa F" uniqKey="Middleton P" first="Philippa F" last="Middleton">Philippa F. Middleton</name>
</noRegion>
<name sortKey="Askie, Lisa" sort="Askie, Lisa" uniqKey="Askie L" first="Lisa" last="Askie">Lisa Askie</name>
<name sortKey="Doyle, Lex W" sort="Doyle, Lex W" uniqKey="Doyle L" first="Lex W" last="Doyle">Lex W. Doyle</name>
</country>
<country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Voysey, Merryn" sort="Voysey, Merryn" uniqKey="Voysey M" first="Merryn" last="Voysey">Merryn Voysey</name>
</region>
<name sortKey="Duley, Lelia" sort="Duley, Lelia" uniqKey="Duley L" first="Lelia" last="Duley">Lelia Duley</name>
</country>
<country name="États-Unis"><region name="Wisconsin"><name sortKey="Pryde, Peter G" sort="Pryde, Peter G" uniqKey="Pryde P" first="Peter G" last="Pryde">Peter G. Pryde</name>
</region>
</country>
<country name="France"><region name="Région Normandie"><name sortKey="Marret, Stephane" sort="Marret, Stephane" uniqKey="Marret S" first="Stéphane" last="Marret">Stéphane Marret</name>
</region>
</country>
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