Serial Monitoring and Hyperimmunoglobulin versus Standard of Care to Prevent Congenital Cytomegalovirus Infection: A Phase III Randomized Trial
Introduction: Nonrandomized studies support the potential of cytomegalovirus hyperimmunoglobulin (CMV-HyperIg) in preventing maternofetal CMV transmission, but prospective interventional studies show equivocal results. We present a prospective phase-III international randomized open-label trial on...
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| Veröffentlicht in: | Fetal diagnosis and therapy 2021-10, Vol.48 (8), p.611-623 |
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| creator | Devlieger, Roland Buxmann, Horst Nigro, Giovanni Enders, Martin Jückstock, Julia Siklós, Pal Wartenberg-Demand, Andrea Schüttrumpf, Jörg Schütze, Joachim Rippel, Natascha Herbold, Marlis Niemann, Gabriele Friese, Klaus |
| description | Introduction: Nonrandomized studies support the potential of cytomegalovirus hyperimmunoglobulin (CMV-HyperIg) in preventing maternofetal CMV transmission, but prospective interventional studies show equivocal results. We present a prospective phase-III international randomized open-label trial on the potential effect of CMV-HyperIg following serial monitoring of CMV serostatus. Methods: CMV-seronegative pregnant women (gestational age [GA] |
| doi_str_mv | 10.1159/000518508 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_gale_infotracmisc_A709901766</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A709901766</galeid><sourcerecordid>A709901766</sourcerecordid><originalsourceid>FETCH-LOGICAL-c460t-961da9e74a9e52a8e3a64c14e8f9dfc892104f95a910830ec15a1c0f2e36fca83</originalsourceid><addsrcrecordid>eNptks-L1DAUgIso7g89ePcQEEQP1aRp2mQPwtB13YEVF3c8h2z60om2yZi0A-M_4b9sygyjC16S8PLley-Pl2UvCH5HCBPvMcaMcIb5o-yUlAXJhajKx-mMCcspp_VJdhbj94TxmlZPsxNaskowyk-z33cQrOrRZ-_s6IN1HVKuRde7TYoPw-R81_v7qbcObSHEKaK7MQEqtMgb1KgAaPToNsAW3Iga7zpIoiRsdqMfoFO939qQni2dAT1a7y7QAt2uVQS0XC7R1yTzg_0FLVrNhTzLnhjVR3h-2M-zb1cfV811fvPl07JZ3OS6rPCYi4q0SkBdpoUVigNVValJCdyI1mguCoJLI5gSBHOKQROmiMamAFoZrTg9zz7svZvpfoBWp-qD6uUmfVqFnfTKyoc3zq5l57eSV0TUNUmCNwdB8D8niKMcbNTQ98qBn6IsGGcC11TMuV7t0dQNkNYZn4x6xuWixkJgUldVol7_Q61B9eM6-n6aexYfgm_3oA4-xgDmWDXBcp4HeZyHv6l_qNBBOJJXl6s9ITetSdTL_1IHyR_Zbry8</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2585907398</pqid></control><display><type>article</type><title>Serial Monitoring and Hyperimmunoglobulin versus Standard of Care to Prevent Congenital Cytomegalovirus Infection: A Phase III Randomized Trial</title><source>Karger Journal Archive Collection</source><source>Karger Journals</source><source>Alma/SFX Local Collection</source><creator>Devlieger, Roland ; Buxmann, Horst ; Nigro, Giovanni ; Enders, Martin ; Jückstock, Julia ; Siklós, Pal ; Wartenberg-Demand, Andrea ; Schüttrumpf, Jörg ; Schütze, Joachim ; Rippel, Natascha ; Herbold, Marlis ; Niemann, Gabriele ; Friese, Klaus</creator><creatorcontrib>Devlieger, Roland ; Buxmann, Horst ; Nigro, Giovanni ; Enders, Martin ; Jückstock, Julia ; Siklós, Pal ; Wartenberg-Demand, Andrea ; Schüttrumpf, Jörg ; Schütze, Joachim ; Rippel, Natascha ; Herbold, Marlis ; Niemann, Gabriele ; Friese, Klaus</creatorcontrib><description>Introduction: Nonrandomized studies support the potential of cytomegalovirus hyperimmunoglobulin (CMV-HyperIg) in preventing maternofetal CMV transmission, but prospective interventional studies show equivocal results. We present a prospective phase-III international randomized open-label trial on the potential effect of CMV-HyperIg following serial monitoring of CMV serostatus. Methods: CMV-seronegative pregnant women (gestational age [GA] <14 weeks) were 1:1 randomized to monthly CMV-serostatus monitoring and CMV-HyperIg upon seroconversion (treatment), or routine prenatal care with CMV-serostatus testing at end of pregnancy (control). Ethical considerations required that control subjects with confirmed seroconversion be offered Cytotect®. The primary endpoint was the proportion of fetuses/newborns with congenital CMV infection. Secondary endpoints included neonatal CMV disease and safety during the 24-month follow-up. Results: The treatment arm counted 4,800 randomized subjects: 52 seroconverted (median GA 24 [11–35] weeks), of which 45 completed follow-up. The control arm counted 4,735 randomized subjects: 42 seroconverted, of which 34 completed follow-up (evaluable data for 28 newborns) and 8 subjects chose off-label Cytotect®. Congenital CMV rates were 13/28 newborns (46.4% [CI 27.51; 66.13]) vs. 16/45 newborns (35.6% [CI 21.87; 51.22]) in control and treated arms, respectively (p = 0.46). Newborn CMV disease was mostly mild and spontaneously resolving. There were no major safety concerns. The target sample was not reached within an acceptable time frame. Conclusions: Serial monitoring of CMV serostatus with CMV-HyperIg treatment was associated with a mild nonsignificant reduction in the vertical CMV transmission rate. Studies on the optimal preventive strategy are hampered by epidemiological and ethical challenges and should focus on GA-dependent transmission rates and accurate dating of infection.</description><identifier>ISSN: 1015-3837</identifier><identifier>EISSN: 1421-9964</identifier><identifier>DOI: 10.1159/000518508</identifier><identifier>PMID: 34569538</identifier><language>eng</language><publisher>Basel, Switzerland: S. Karger AG</publisher><subject>Care and treatment ; Cytomegalovirus infections ; Diagnosis ; Disease transmission ; Diseases ; Health aspects ; Infants (Newborn) ; Pregnant women ; Prevention ; Research Article ; Risk factors</subject><ispartof>Fetal diagnosis and therapy, 2021-10, Vol.48 (8), p.611-623</ispartof><rights>The Author(s). Published by S. Karger AG, Basel</rights><rights>COPYRIGHT 2021 S. Karger AG</rights><rights>Copyright © 2021 by S. Karger AG, Basel 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c460t-961da9e74a9e52a8e3a64c14e8f9dfc892104f95a910830ec15a1c0f2e36fca83</citedby><cites>FETCH-LOGICAL-c460t-961da9e74a9e52a8e3a64c14e8f9dfc892104f95a910830ec15a1c0f2e36fca83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,2423,27901,27902</link.rule.ids></links><search><creatorcontrib>Devlieger, Roland</creatorcontrib><creatorcontrib>Buxmann, Horst</creatorcontrib><creatorcontrib>Nigro, Giovanni</creatorcontrib><creatorcontrib>Enders, Martin</creatorcontrib><creatorcontrib>Jückstock, Julia</creatorcontrib><creatorcontrib>Siklós, Pal</creatorcontrib><creatorcontrib>Wartenberg-Demand, Andrea</creatorcontrib><creatorcontrib>Schüttrumpf, Jörg</creatorcontrib><creatorcontrib>Schütze, Joachim</creatorcontrib><creatorcontrib>Rippel, Natascha</creatorcontrib><creatorcontrib>Herbold, Marlis</creatorcontrib><creatorcontrib>Niemann, Gabriele</creatorcontrib><creatorcontrib>Friese, Klaus</creatorcontrib><title>Serial Monitoring and Hyperimmunoglobulin versus Standard of Care to Prevent Congenital Cytomegalovirus Infection: A Phase III Randomized Trial</title><title>Fetal diagnosis and therapy</title><addtitle>Fetal Diagn Ther</addtitle><description>Introduction: Nonrandomized studies support the potential of cytomegalovirus hyperimmunoglobulin (CMV-HyperIg) in preventing maternofetal CMV transmission, but prospective interventional studies show equivocal results. We present a prospective phase-III international randomized open-label trial on the potential effect of CMV-HyperIg following serial monitoring of CMV serostatus. Methods: CMV-seronegative pregnant women (gestational age [GA] <14 weeks) were 1:1 randomized to monthly CMV-serostatus monitoring and CMV-HyperIg upon seroconversion (treatment), or routine prenatal care with CMV-serostatus testing at end of pregnancy (control). Ethical considerations required that control subjects with confirmed seroconversion be offered Cytotect®. The primary endpoint was the proportion of fetuses/newborns with congenital CMV infection. Secondary endpoints included neonatal CMV disease and safety during the 24-month follow-up. Results: The treatment arm counted 4,800 randomized subjects: 52 seroconverted (median GA 24 [11–35] weeks), of which 45 completed follow-up. The control arm counted 4,735 randomized subjects: 42 seroconverted, of which 34 completed follow-up (evaluable data for 28 newborns) and 8 subjects chose off-label Cytotect®. Congenital CMV rates were 13/28 newborns (46.4% [CI 27.51; 66.13]) vs. 16/45 newborns (35.6% [CI 21.87; 51.22]) in control and treated arms, respectively (p = 0.46). Newborn CMV disease was mostly mild and spontaneously resolving. There were no major safety concerns. The target sample was not reached within an acceptable time frame. Conclusions: Serial monitoring of CMV serostatus with CMV-HyperIg treatment was associated with a mild nonsignificant reduction in the vertical CMV transmission rate. Studies on the optimal preventive strategy are hampered by epidemiological and ethical challenges and should focus on GA-dependent transmission rates and accurate dating of infection.</description><subject>Care and treatment</subject><subject>Cytomegalovirus infections</subject><subject>Diagnosis</subject><subject>Disease transmission</subject><subject>Diseases</subject><subject>Health aspects</subject><subject>Infants (Newborn)</subject><subject>Pregnant women</subject><subject>Prevention</subject><subject>Research Article</subject><subject>Risk factors</subject><issn>1015-3837</issn><issn>1421-9964</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>M--</sourceid><recordid>eNptks-L1DAUgIso7g89ePcQEEQP1aRp2mQPwtB13YEVF3c8h2z60om2yZi0A-M_4b9sygyjC16S8PLley-Pl2UvCH5HCBPvMcaMcIb5o-yUlAXJhajKx-mMCcspp_VJdhbj94TxmlZPsxNaskowyk-z33cQrOrRZ-_s6IN1HVKuRde7TYoPw-R81_v7qbcObSHEKaK7MQEqtMgb1KgAaPToNsAW3Iga7zpIoiRsdqMfoFO939qQni2dAT1a7y7QAt2uVQS0XC7R1yTzg_0FLVrNhTzLnhjVR3h-2M-zb1cfV811fvPl07JZ3OS6rPCYi4q0SkBdpoUVigNVValJCdyI1mguCoJLI5gSBHOKQROmiMamAFoZrTg9zz7svZvpfoBWp-qD6uUmfVqFnfTKyoc3zq5l57eSV0TUNUmCNwdB8D8niKMcbNTQ98qBn6IsGGcC11TMuV7t0dQNkNYZn4x6xuWixkJgUldVol7_Q61B9eM6-n6aexYfgm_3oA4-xgDmWDXBcp4HeZyHv6l_qNBBOJJXl6s9ITetSdTL_1IHyR_Zbry8</recordid><startdate>20211001</startdate><enddate>20211001</enddate><creator>Devlieger, Roland</creator><creator>Buxmann, Horst</creator><creator>Nigro, Giovanni</creator><creator>Enders, Martin</creator><creator>Jückstock, Julia</creator><creator>Siklós, Pal</creator><creator>Wartenberg-Demand, Andrea</creator><creator>Schüttrumpf, Jörg</creator><creator>Schütze, Joachim</creator><creator>Rippel, Natascha</creator><creator>Herbold, Marlis</creator><creator>Niemann, Gabriele</creator><creator>Friese, Klaus</creator><general>S. Karger AG</general><scope>M--</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20211001</creationdate><title>Serial Monitoring and Hyperimmunoglobulin versus Standard of Care to Prevent Congenital Cytomegalovirus Infection: A Phase III Randomized Trial</title><author>Devlieger, Roland ; Buxmann, Horst ; Nigro, Giovanni ; Enders, Martin ; Jückstock, Julia ; Siklós, Pal ; Wartenberg-Demand, Andrea ; Schüttrumpf, Jörg ; Schütze, Joachim ; Rippel, Natascha ; Herbold, Marlis ; Niemann, Gabriele ; Friese, Klaus</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c460t-961da9e74a9e52a8e3a64c14e8f9dfc892104f95a910830ec15a1c0f2e36fca83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Care and treatment</topic><topic>Cytomegalovirus infections</topic><topic>Diagnosis</topic><topic>Disease transmission</topic><topic>Diseases</topic><topic>Health aspects</topic><topic>Infants (Newborn)</topic><topic>Pregnant women</topic><topic>Prevention</topic><topic>Research Article</topic><topic>Risk factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Devlieger, Roland</creatorcontrib><creatorcontrib>Buxmann, Horst</creatorcontrib><creatorcontrib>Nigro, Giovanni</creatorcontrib><creatorcontrib>Enders, Martin</creatorcontrib><creatorcontrib>Jückstock, Julia</creatorcontrib><creatorcontrib>Siklós, Pal</creatorcontrib><creatorcontrib>Wartenberg-Demand, Andrea</creatorcontrib><creatorcontrib>Schüttrumpf, Jörg</creatorcontrib><creatorcontrib>Schütze, Joachim</creatorcontrib><creatorcontrib>Rippel, Natascha</creatorcontrib><creatorcontrib>Herbold, Marlis</creatorcontrib><creatorcontrib>Niemann, Gabriele</creatorcontrib><creatorcontrib>Friese, Klaus</creatorcontrib><collection>Karger Open Access</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Fetal diagnosis and therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Devlieger, Roland</au><au>Buxmann, Horst</au><au>Nigro, Giovanni</au><au>Enders, Martin</au><au>Jückstock, Julia</au><au>Siklós, Pal</au><au>Wartenberg-Demand, Andrea</au><au>Schüttrumpf, Jörg</au><au>Schütze, Joachim</au><au>Rippel, Natascha</au><au>Herbold, Marlis</au><au>Niemann, Gabriele</au><au>Friese, Klaus</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Serial Monitoring and Hyperimmunoglobulin versus Standard of Care to Prevent Congenital Cytomegalovirus Infection: A Phase III Randomized Trial</atitle><jtitle>Fetal diagnosis and therapy</jtitle><addtitle>Fetal Diagn Ther</addtitle><date>2021-10-01</date><risdate>2021</risdate><volume>48</volume><issue>8</issue><spage>611</spage><epage>623</epage><pages>611-623</pages><issn>1015-3837</issn><eissn>1421-9964</eissn><abstract>Introduction: Nonrandomized studies support the potential of cytomegalovirus hyperimmunoglobulin (CMV-HyperIg) in preventing maternofetal CMV transmission, but prospective interventional studies show equivocal results. We present a prospective phase-III international randomized open-label trial on the potential effect of CMV-HyperIg following serial monitoring of CMV serostatus. Methods: CMV-seronegative pregnant women (gestational age [GA] <14 weeks) were 1:1 randomized to monthly CMV-serostatus monitoring and CMV-HyperIg upon seroconversion (treatment), or routine prenatal care with CMV-serostatus testing at end of pregnancy (control). Ethical considerations required that control subjects with confirmed seroconversion be offered Cytotect®. The primary endpoint was the proportion of fetuses/newborns with congenital CMV infection. Secondary endpoints included neonatal CMV disease and safety during the 24-month follow-up. Results: The treatment arm counted 4,800 randomized subjects: 52 seroconverted (median GA 24 [11–35] weeks), of which 45 completed follow-up. The control arm counted 4,735 randomized subjects: 42 seroconverted, of which 34 completed follow-up (evaluable data for 28 newborns) and 8 subjects chose off-label Cytotect®. Congenital CMV rates were 13/28 newborns (46.4% [CI 27.51; 66.13]) vs. 16/45 newborns (35.6% [CI 21.87; 51.22]) in control and treated arms, respectively (p = 0.46). Newborn CMV disease was mostly mild and spontaneously resolving. There were no major safety concerns. The target sample was not reached within an acceptable time frame. Conclusions: Serial monitoring of CMV serostatus with CMV-HyperIg treatment was associated with a mild nonsignificant reduction in the vertical CMV transmission rate. Studies on the optimal preventive strategy are hampered by epidemiological and ethical challenges and should focus on GA-dependent transmission rates and accurate dating of infection.</abstract><cop>Basel, Switzerland</cop><pub>S. Karger AG</pub><pmid>34569538</pmid><doi>10.1159/000518508</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Fetal diagnosis and therapy, 2021-10, Vol.48 (8), p.611-623 |
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| source | Karger Journal Archive Collection; Karger Journals; Alma/SFX Local Collection |
| subjects | Care and treatment Cytomegalovirus infections Diagnosis Disease transmission Diseases Health aspects Infants (Newborn) Pregnant women Prevention Research Article Risk factors |
| title | Serial Monitoring and Hyperimmunoglobulin versus Standard of Care to Prevent Congenital Cytomegalovirus Infection: A Phase III Randomized Trial |
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