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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Pregnancy outcome after TNF-α inhibitor therapy during the first trimester: a prospective multicentre cohort study</title><author><name sortKey="Weber Schoendorfer, Corinna" sort="Weber Schoendorfer, Corinna" uniqKey="Weber Schoendorfer C" first="Corinna" last="Weber-Schoendorfer">Corinna Weber-Schoendorfer</name><affiliation><nlm:aff id="au1"><institution>Pharmakovigilanzzentrum Embryonaltoxikologie, Institut für Klinische Pharmakologie und Toxikologie, Charité Universitätsmedizin Berlin</institution><addr-line>Berlin, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Oppermann, Marc" sort="Oppermann, Marc" uniqKey="Oppermann M" first="Marc" last="Oppermann">Marc Oppermann</name><affiliation><nlm:aff id="au1"><institution>Pharmakovigilanzzentrum Embryonaltoxikologie, Institut für Klinische Pharmakologie und Toxikologie, Charité Universitätsmedizin Berlin</institution><addr-line>Berlin, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Wacker, Evelin" sort="Wacker, Evelin" uniqKey="Wacker E" first="Evelin" last="Wacker">Evelin Wacker</name><affiliation><nlm:aff id="au1"><institution>Pharmakovigilanzzentrum Embryonaltoxikologie, Institut für Klinische Pharmakologie und Toxikologie, Charité Universitätsmedizin Berlin</institution><addr-line>Berlin, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Bernard, Nathalie" sort="Bernard, Nathalie" uniqKey="Bernard N" first="Nathalie" last="Bernard">Nathalie Bernard</name><affiliation><nlm:aff id="au2"><institution>Centre Régional de Pharmacovigilance, Hospices Civils de Lyon</institution><addr-line>Lyon, France</addr-line></nlm:aff></affiliation></author><author><name sortKey="Beghin, Delphine" sort="Beghin, Delphine" uniqKey="Beghin D" first="Delphine" last="Beghin">Delphine Beghin</name></author><author><name sortKey="Cuppers Maarschalkerweerd, Benedikte" sort="Cuppers Maarschalkerweerd, Benedikte" uniqKey="Cuppers Maarschalkerweerd B" first="Benedikte" last="Cuppers-Maarschalkerweerd">Benedikte Cuppers-Maarschalkerweerd</name><affiliation><nlm:aff id="au4"><institution>Teratology Information Service, MH ’s-Hertogenbosch</institution><addr-line>Netherlands</addr-line></nlm:aff></affiliation></author><author><name sortKey="Richardson, Jonathan L" sort="Richardson, Jonathan L" uniqKey="Richardson J" first="Jonathan L" last="Richardson">Jonathan L. Richardson</name><affiliation><nlm:aff id="au5"><institution>UK Teratology Information Service, Newcastle upon Tyne Hospitals NHS Foundation Trust & Newcastle University</institution><addr-line>Newcastle upon Tyne, United Kingdom</addr-line></nlm:aff></affiliation></author><author><name sortKey="Rothuizen, Laura E" sort="Rothuizen, Laura E" uniqKey="Rothuizen L" first="Laura E" last="Rothuizen">Laura E. Rothuizen</name><affiliation><nlm:aff id="au6"><institution>Swiss Teratogen Information Service (STIS) and Division of Clinical Pharmacology, University Hospital</institution><addr-line>Lausanne, Switzerland</addr-line></nlm:aff></affiliation></author><author><name sortKey="Pistelli, Alessandra" sort="Pistelli, Alessandra" uniqKey="Pistelli A" first="Alessandra" last="Pistelli">Alessandra Pistelli</name><affiliation><nlm:aff id="au7"><institution>Centro di Riferimento Regionale di Tossicologia Perinatale, Azienda Ospedaliero Universitaria Careggi</institution><addr-line>Firenze, Italy</addr-line></nlm:aff></affiliation></author><author><name sortKey="Malm, Heli" sort="Malm, Heli" uniqKey="Malm H" first="Heli" last="Malm">Heli Malm</name><affiliation><nlm:aff id="au8"><institution>Teratology Information Service, HUSLAB and Helsinki University Central Hospital</institution><addr-line>Helsinki, Finland</addr-line></nlm:aff></affiliation></author><author><name sortKey="Eleftheriou, Georgios" sort="Eleftheriou, Georgios" uniqKey="Eleftheriou G" first="Georgios" last="Eleftheriou">Georgios Eleftheriou</name><affiliation><nlm:aff id="au9"><institution>Poison Control Centre and Teratology Information Service, Hospital Papa Giovanni XXIII</institution><addr-line>Bergamo, Italy</addr-line></nlm:aff></affiliation></author><author><name sortKey="Kennedy, Debra" sort="Kennedy, Debra" uniqKey="Kennedy D" first="Debra" last="Kennedy">Debra Kennedy</name><affiliation><nlm:aff id="au10"><institution>Mothersafe, Royal Hospital for Women</institution><addr-line>Randwick, Australia</addr-line></nlm:aff></affiliation></author><author><name sortKey="Kadioglu Duman, Mine" sort="Kadioglu Duman, Mine" uniqKey="Kadioglu Duman M" first="Mine" last="Kadioglu Duman">Mine Kadioglu Duman</name><affiliation><nlm:aff id="au11"><institution>Department of Pharmacology, Karadeniz Technical University</institution><addr-line>Trabzon, Turkey</addr-line></nlm:aff></affiliation></author><author><name sortKey="Meister, Reinhard" sort="Meister, Reinhard" uniqKey="Meister R" first="Reinhard" last="Meister">Reinhard Meister</name><affiliation><nlm:aff id="au12"><institution>Department of Mathematics, Beuth Hochschule für Technik Berlin (University of Applied Sciences)</institution><addr-line>Berlin, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Schaefer, Christof" sort="Schaefer, Christof" uniqKey="Schaefer C" first="Christof" last="Schaefer">Christof Schaefer</name><affiliation><nlm:aff id="au1"><institution>Pharmakovigilanzzentrum Embryonaltoxikologie, Institut für Klinische Pharmakologie und Toxikologie, Charité Universitätsmedizin Berlin</institution><addr-line>Berlin, Germany</addr-line></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25808588</idno><idno type="pmc">4594709</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4594709</idno><idno type="RBID">PMC:4594709</idno><idno type="doi">10.1111/bcp.12642</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">000175</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000175</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Pregnancy outcome after TNF-α inhibitor therapy during the first trimester: a prospective multicentre cohort study</title><author><name sortKey="Weber Schoendorfer, Corinna" sort="Weber Schoendorfer, Corinna" uniqKey="Weber Schoendorfer C" first="Corinna" last="Weber-Schoendorfer">Corinna Weber-Schoendorfer</name><affiliation><nlm:aff id="au1"><institution>Pharmakovigilanzzentrum Embryonaltoxikologie, Institut für Klinische Pharmakologie und Toxikologie, Charité Universitätsmedizin Berlin</institution><addr-line>Berlin, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Oppermann, Marc" sort="Oppermann, Marc" uniqKey="Oppermann M" first="Marc" last="Oppermann">Marc Oppermann</name><affiliation><nlm:aff id="au1"><institution>Pharmakovigilanzzentrum Embryonaltoxikologie, Institut für Klinische Pharmakologie und Toxikologie, Charité Universitätsmedizin Berlin</institution><addr-line>Berlin, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Wacker, Evelin" sort="Wacker, Evelin" uniqKey="Wacker E" first="Evelin" last="Wacker">Evelin Wacker</name><affiliation><nlm:aff id="au1"><institution>Pharmakovigilanzzentrum Embryonaltoxikologie, Institut für Klinische Pharmakologie und Toxikologie, Charité Universitätsmedizin Berlin</institution><addr-line>Berlin, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Bernard, Nathalie" sort="Bernard, Nathalie" uniqKey="Bernard N" first="Nathalie" last="Bernard">Nathalie Bernard</name><affiliation><nlm:aff id="au2"><institution>Centre Régional de Pharmacovigilance, Hospices Civils de Lyon</institution><addr-line>Lyon, France</addr-line></nlm:aff></affiliation></author><author><name sortKey="Beghin, Delphine" sort="Beghin, Delphine" uniqKey="Beghin D" first="Delphine" last="Beghin">Delphine Beghin</name></author><author><name sortKey="Cuppers Maarschalkerweerd, Benedikte" sort="Cuppers Maarschalkerweerd, Benedikte" uniqKey="Cuppers Maarschalkerweerd B" first="Benedikte" last="Cuppers-Maarschalkerweerd">Benedikte Cuppers-Maarschalkerweerd</name><affiliation><nlm:aff id="au4"><institution>Teratology Information Service, MH ’s-Hertogenbosch</institution><addr-line>Netherlands</addr-line></nlm:aff></affiliation></author><author><name sortKey="Richardson, Jonathan L" sort="Richardson, Jonathan L" uniqKey="Richardson J" first="Jonathan L" last="Richardson">Jonathan L. Richardson</name><affiliation><nlm:aff id="au5"><institution>UK Teratology Information Service, Newcastle upon Tyne Hospitals NHS Foundation Trust & Newcastle University</institution><addr-line>Newcastle upon Tyne, United Kingdom</addr-line></nlm:aff></affiliation></author><author><name sortKey="Rothuizen, Laura E" sort="Rothuizen, Laura E" uniqKey="Rothuizen L" first="Laura E" last="Rothuizen">Laura E. Rothuizen</name><affiliation><nlm:aff id="au6"><institution>Swiss Teratogen Information Service (STIS) and Division of Clinical Pharmacology, University Hospital</institution><addr-line>Lausanne, Switzerland</addr-line></nlm:aff></affiliation></author><author><name sortKey="Pistelli, Alessandra" sort="Pistelli, Alessandra" uniqKey="Pistelli A" first="Alessandra" last="Pistelli">Alessandra Pistelli</name><affiliation><nlm:aff id="au7"><institution>Centro di Riferimento Regionale di Tossicologia Perinatale, Azienda Ospedaliero Universitaria Careggi</institution><addr-line>Firenze, Italy</addr-line></nlm:aff></affiliation></author><author><name sortKey="Malm, Heli" sort="Malm, Heli" uniqKey="Malm H" first="Heli" last="Malm">Heli Malm</name><affiliation><nlm:aff id="au8"><institution>Teratology Information Service, HUSLAB and Helsinki University Central Hospital</institution><addr-line>Helsinki, Finland</addr-line></nlm:aff></affiliation></author><author><name sortKey="Eleftheriou, Georgios" sort="Eleftheriou, Georgios" uniqKey="Eleftheriou G" first="Georgios" last="Eleftheriou">Georgios Eleftheriou</name><affiliation><nlm:aff id="au9"><institution>Poison Control Centre and Teratology Information Service, Hospital Papa Giovanni XXIII</institution><addr-line>Bergamo, Italy</addr-line></nlm:aff></affiliation></author><author><name sortKey="Kennedy, Debra" sort="Kennedy, Debra" uniqKey="Kennedy D" first="Debra" last="Kennedy">Debra Kennedy</name><affiliation><nlm:aff id="au10"><institution>Mothersafe, Royal Hospital for Women</institution><addr-line>Randwick, Australia</addr-line></nlm:aff></affiliation></author><author><name sortKey="Kadioglu Duman, Mine" sort="Kadioglu Duman, Mine" uniqKey="Kadioglu Duman M" first="Mine" last="Kadioglu Duman">Mine Kadioglu Duman</name><affiliation><nlm:aff id="au11"><institution>Department of Pharmacology, Karadeniz Technical University</institution><addr-line>Trabzon, Turkey</addr-line></nlm:aff></affiliation></author><author><name sortKey="Meister, Reinhard" sort="Meister, Reinhard" uniqKey="Meister R" first="Reinhard" last="Meister">Reinhard Meister</name><affiliation><nlm:aff id="au12"><institution>Department of Mathematics, Beuth Hochschule für Technik Berlin (University of Applied Sciences)</institution><addr-line>Berlin, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Schaefer, Christof" sort="Schaefer, Christof" uniqKey="Schaefer C" first="Christof" last="Schaefer">Christof Schaefer</name><affiliation><nlm:aff id="au1"><institution>Pharmakovigilanzzentrum Embryonaltoxikologie, Institut für Klinische Pharmakologie und Toxikologie, Charité Universitätsmedizin Berlin</institution><addr-line>Berlin, Germany</addr-line></nlm:aff></affiliation></author></analytic><series><title level="j">British Journal of Clinical Pharmacology</title><idno type="ISSN">0306-5251</idno><idno type="eISSN">1365-2125</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Aims</title><p>TNF-α inhibitors are considered relatively safe in pregnancy but experience is still limited. The aim of this study was to evaluate the risk of major birth defects, spontaneous abortion, preterm birth and reduced birth weight after first trimester exposure to TNF-α inhibitors.</p></sec><sec><title>Methods</title><p>Pregnancy outcomes of women on adalimumab, infliximab, etanercept, certolizumab pegol or golimumab were evaluated in a prospective observational cohort study and compared with outcomes of a non-exposed random sample. The samples were drawn from pregnancies identified by institutes collaborating in the European Network of Teratology Information Services.</p></sec><sec><title>Results</title><p>In total, 495 exposed and 1532 comparison pregnancies were contributed from nine countries. The risk of major birth defects was increased in the exposed (5.0%) compared with the non-exposed group (1.5%; adjusted odds ratio (OR<sub>adj</sub>) 2.2, 95% CI 1.0, 4.8). The risk of preterm birth was increased (17.6%; OR<sub>adj</sub> 1.69, 95% CI 1.1, 2.5), but not the risk of spontaneous abortion (16.2%; adjusted hazard ratio [HR<sub>adj</sub>] 1.06, 95% CI 0.7, 1.7). Birth weights adjusted for gestational age and sex were significantly lower in the exposed group compared to the non-exposed cohort (<italic>P</italic> = 0.02). As a diseased comparison group was not possible to ascertain, the influence of disease and treatment on birth weight and preterm birth could not be differentiated.</p></sec><sec><title>Conclusions</title><p>TNF-α inhibitors may carry a risk of adverse pregnancy outcome of moderate clinical relevance. Considering the impact of insufficiently controlled autoimmune disease on the mother and the unborn child, TNF-α inhibitors may nevertheless be a treatment option in women with severe disease refractory to established immunomodulatory drugs.</p></sec></div></front></TEI><pmc article-type="research-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">Br J Clin Pharmacol</journal-id><journal-id journal-id-type="iso-abbrev">Br J Clin Pharmacol</journal-id><journal-id journal-id-type="publisher-id">bcp</journal-id><journal-title-group><journal-title>British Journal of Clinical Pharmacology</journal-title></journal-title-group><issn pub-type="ppub">0306-5251</issn><issn pub-type="epub">1365-2125</issn><publisher><publisher-name>John Wiley & Sons, Ltd</publisher-name><publisher-loc>Chichester, UK</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">25808588</article-id><article-id pub-id-type="pmc">4594709</article-id><article-id pub-id-type="doi">10.1111/bcp.12642</article-id><article-categories><subj-group subj-group-type="heading"><subject>Drugs in Pregnancy and Lactation</subject></subj-group></article-categories><title-group><article-title>Pregnancy outcome after TNF-α inhibitor therapy during the first trimester: a prospective multicentre cohort study</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Weber-Schoendorfer</surname><given-names>Corinna</given-names></name><xref ref-type="aff" rid="au1">1</xref><xref ref-type="author-notes" rid="fn1">*</xref><xref ref-type="corresp" rid="cor1"></xref></contrib><contrib contrib-type="author"><name><surname>Oppermann</surname><given-names>Marc</given-names></name><xref ref-type="aff" rid="au1">1</xref><xref ref-type="author-notes" rid="fn1">*</xref></contrib><contrib contrib-type="author"><name><surname>Wacker</surname><given-names>Evelin</given-names></name><xref ref-type="aff" rid="au1">1</xref></contrib><contrib contrib-type="author"><name><surname>Bernard</surname><given-names>Nathalie</given-names></name><xref ref-type="aff" rid="au2">2</xref></contrib><contrib contrib-type="author"><name><surname>Beghin</surname><given-names>Delphine</given-names></name></contrib><contrib contrib-type="author"><name><surname>Cuppers-Maarschalkerweerd</surname><given-names>Benedikte</given-names></name><xref ref-type="aff" rid="au4">4</xref></contrib><contrib contrib-type="author"><name><surname>Richardson</surname><given-names>Jonathan L</given-names></name><xref ref-type="aff" rid="au5">5</xref></contrib><contrib contrib-type="author"><name><surname>Rothuizen</surname><given-names>Laura E</given-names></name><xref ref-type="aff" rid="au6">6</xref></contrib><contrib contrib-type="author"><name><surname>Pistelli</surname><given-names>Alessandra</given-names></name><xref ref-type="aff" rid="au7">7</xref></contrib><contrib contrib-type="author"><name><surname>Malm</surname><given-names>Heli</given-names></name><xref ref-type="aff" rid="au8">8</xref></contrib><contrib contrib-type="author"><name><surname>Eleftheriou</surname><given-names>Georgios</given-names></name><xref ref-type="aff" rid="au9">9</xref></contrib><contrib contrib-type="author"><name><surname>Kennedy</surname><given-names>Debra</given-names></name><xref ref-type="aff" rid="au10">10</xref></contrib><contrib contrib-type="author"><name><surname>Kadioglu Duman</surname><given-names>Mine</given-names></name><xref ref-type="aff" rid="au11">11</xref></contrib><contrib contrib-type="author"><name><surname>Meister</surname><given-names>Reinhard</given-names></name><xref ref-type="aff" rid="au12">12</xref></contrib><contrib contrib-type="author"><name><surname>Schaefer</surname><given-names>Christof</given-names></name><xref ref-type="aff" rid="au1">1</xref></contrib><aff id="au1"><label>1</label><institution>Pharmakovigilanzzentrum Embryonaltoxikologie, Institut für Klinische Pharmakologie und Toxikologie, Charité Universitätsmedizin Berlin</institution><addr-line>Berlin, Germany</addr-line></aff><aff id="au2"><label>2</label><institution>Centre Régional de Pharmacovigilance, Hospices Civils de Lyon</institution><addr-line>Lyon, France</addr-line></aff><aff id="au3"><label>3</label><institution>Centre de Référence sur les Agents Tératogènes (CRAT), Hôpitaux Universitaires Est Parisien (APHP)</institution><addr-line>Paris, France</addr-line></aff><aff id="au4"><label>4</label><institution>Teratology Information Service, MH ’s-Hertogenbosch</institution><addr-line>Netherlands</addr-line></aff><aff id="au5"><label>5</label><institution>UK Teratology Information Service, Newcastle upon Tyne Hospitals NHS Foundation Trust & Newcastle University</institution><addr-line>Newcastle upon Tyne, United Kingdom</addr-line></aff><aff id="au6"><label>6</label><institution>Swiss Teratogen Information Service (STIS) and Division of Clinical Pharmacology, University Hospital</institution><addr-line>Lausanne, Switzerland</addr-line></aff><aff id="au7"><label>7</label><institution>Centro di Riferimento Regionale di Tossicologia Perinatale, Azienda Ospedaliero Universitaria Careggi</institution><addr-line>Firenze, Italy</addr-line></aff><aff id="au8"><label>8</label><institution>Teratology Information Service, HUSLAB and Helsinki University Central Hospital</institution><addr-line>Helsinki, Finland</addr-line></aff><aff id="au9"><label>9</label><institution>Poison Control Centre and Teratology Information Service, Hospital Papa Giovanni XXIII</institution><addr-line>Bergamo, Italy</addr-line></aff><aff id="au10"><label>10</label><institution>Mothersafe, Royal Hospital for Women</institution><addr-line>Randwick, Australia</addr-line></aff><aff id="au11"><label>11</label><institution>Department of Pharmacology, Karadeniz Technical University</institution><addr-line>Trabzon, Turkey</addr-line></aff><aff id="au12"><label>12</label><institution>Department of Mathematics, Beuth Hochschule für Technik Berlin (University of Applied Sciences)</institution><addr-line>Berlin, Germany</addr-line></aff></contrib-group><author-notes><corresp id="cor1"><bold>Correspondence</bold>, Dr Corinna Weber-Schoendorfer, Pharmakovigilanz- und Beratungszentrum für Embryonaltoxikologie, Charité Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany., Tel.: +49 30 450525711, Fax: +49 30 450525902, E-mail: <email>corinna.weber-schoendorfer@charite.de</email></corresp><fn id="fn1"><label>*</label><p>Both authors contributed equally to this article</p></fn><fn><p>Principal investigator: Christof Schaefer</p></fn></author-notes><pub-date pub-type="ppub"><month>10</month><year>2015</year></pub-date><pub-date pub-type="epub"><day>28</day><month>5</month><year>2015</year></pub-date><volume>80</volume><issue>4</issue><fpage>727</fpage><lpage>739</lpage><history><date date-type="received"><day>07</day><month>1</month><year>2015</year></date><date date-type="accepted"><day>21</day><month>3</month><year>2015</year></date></history><permissions><copyright-statement>© 2015 The British Pharmacological Society</copyright-statement><copyright-year>2015</copyright-year></permissions><abstract><sec><title>Aims</title><p>TNF-α inhibitors are considered relatively safe in pregnancy but experience is still limited. The aim of this study was to evaluate the risk of major birth defects, spontaneous abortion, preterm birth and reduced birth weight after first trimester exposure to TNF-α inhibitors.</p></sec><sec><title>Methods</title><p>Pregnancy outcomes of women on adalimumab, infliximab, etanercept, certolizumab pegol or golimumab were evaluated in a prospective observational cohort study and compared with outcomes of a non-exposed random sample. The samples were drawn from pregnancies identified by institutes collaborating in the European Network of Teratology Information Services.</p></sec><sec><title>Results</title><p>In total, 495 exposed and 1532 comparison pregnancies were contributed from nine countries. The risk of major birth defects was increased in the exposed (5.0%) compared with the non-exposed group (1.5%; adjusted odds ratio (OR<sub>adj</sub>) 2.2, 95% CI 1.0, 4.8). The risk of preterm birth was increased (17.6%; OR<sub>adj</sub> 1.69, 95% CI 1.1, 2.5), but not the risk of spontaneous abortion (16.2%; adjusted hazard ratio [HR<sub>adj</sub>] 1.06, 95% CI 0.7, 1.7). Birth weights adjusted for gestational age and sex were significantly lower in the exposed group compared to the non-exposed cohort (<italic>P</italic> = 0.02). As a diseased comparison group was not possible to ascertain, the influence of disease and treatment on birth weight and preterm birth could not be differentiated.</p></sec><sec><title>Conclusions</title><p>TNF-α inhibitors may carry a risk of adverse pregnancy outcome of moderate clinical relevance. Considering the impact of insufficiently controlled autoimmune disease on the mother and the unborn child, TNF-α inhibitors may nevertheless be a treatment option in women with severe disease refractory to established immunomodulatory drugs.</p></sec></abstract><kwd-group><kwd>TNF-α inhibitors</kwd><kwd>pregnancy outcome</kwd><kwd>birth defects</kwd><kwd>malformations</kwd><kwd>birth weight</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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