{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T23:04:46Z","timestamp":1784934286708,"version":"3.55.0"},"reference-count":23,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,8,2]],"date-time":"2024-08-02T00:00:00Z","timestamp":1722556800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Primary cytomegalovirus infection during pregnancy has a high risk of vertical transmission, with severe fetal sequelae mainly associated with first-trimester infections. We conducted a retrospective analysis of 200 IU\/kg cytomegalovirus-specific hyperimmune globulin (HIG), used in first-trimester maternal primary infections for congenital infection prevention. The primary outcome was vertical transmission, defined as neonatal viruria or positive amniocentesis if pregnancy was discontinued. HIG, initially administered monthly and since 2019 biweekly, was discontinued in negative amniocentesis cases. Women declining amniocentesis and positive amniocentesis cases with normal sonography were offered monthly HIG until delivery as a treatment strategy. The total transmission rate was 29.9% (32\/107; 10 pregnancy terminations with positive amniocentesis, 18 completed pregnancies with positive amniocentesis and 4 declining amniocentesis). Maternal viremia was the only factor associated with fetal transmission (OR 4.62, 95% CI 1.55\u201313.74). The transmission rate was not significantly different whether HIG was started during the first or second trimester (28.2% vs. 33.3%; p = 0.58), or between monthly and biweekly subgroups (25.7% vs. 37.8%, p = 0.193). Pre-treatment maternal viremia could inform decisions as a predictor of congenital infection.<\/jats:p>","DOI":"10.3390\/v16081241","type":"journal-article","created":{"date-parts":[[2024,8,2]],"date-time":"2024-08-02T09:34:17Z","timestamp":1722591257000},"page":"1241","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Cytomegalovirus-Specific Hyperimmune Immunoglobulin Administration for Secondary Prevention after First-Trimester Maternal Primary Infection: A 13-Year Single-Center Cohort Study"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3034-8337","authenticated-orcid":false,"given":"Emmanouil","family":"Karofylakis","sequence":"first","affiliation":[{"name":"Fourth Department of Internal Medicine, University General Hospital Attikon, National and Kapodistrian University of Athens, 12462 Athens, Greece"},{"name":"Department of Infectious Diseases, Addenbrooke\u2019s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7489-7776","authenticated-orcid":false,"given":"Konstantinos","family":"Thomas","sequence":"additional","affiliation":[{"name":"Fourth Department of Internal Medicine, University General Hospital Attikon, National and Kapodistrian University of Athens, 12462 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitra","family":"Kavatha","sequence":"additional","affiliation":[{"name":"Fourth Department of Internal Medicine, University General Hospital Attikon, National and Kapodistrian University of Athens, 12462 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0418-1111","authenticated-orcid":false,"given":"Lamprini","family":"Galani","sequence":"additional","affiliation":[{"name":"1st Department of Internal Medicine-Infectious Diseases, Hygeia General Hospital, 4 Erythrou Stavrou & Kifisias, Marousi, 15123 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0463-4321","authenticated-orcid":false,"given":"Sotirios","family":"Tsiodras","sequence":"additional","affiliation":[{"name":"Fourth Department of Internal Medicine, University General Hospital Attikon, National and Kapodistrian University of Athens, 12462 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Giamarellou","sequence":"additional","affiliation":[{"name":"1st Department of Internal Medicine-Infectious Diseases, Hygeia General Hospital, 4 Erythrou Stavrou & Kifisias, Marousi, 15123 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vassiliki","family":"Papaevangelou","sequence":"additional","affiliation":[{"name":"Third Department of Pediatrics, University General Hospital Attikon, National and Kapodistrian University of Athens, 12462 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0991-9198","authenticated-orcid":false,"given":"Anastasia","family":"Antoniadou","sequence":"additional","affiliation":[{"name":"Fourth Department of Internal Medicine, University General Hospital Attikon, National and Kapodistrian University of Athens, 12462 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1128\/CMR.00062-12","article-title":"The \u201cSilent\u201d Global Burden of Congenital Cytomegalovirus","volume":"26","author":"Manicklal","year":"2013","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1542\/peds.2014-1173","article-title":"Hearing Loss and Congenital CMV Infection: A Systematic Review","volume":"134","author":"Goderis","year":"2014","journal-title":"Pediatrics"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e2120736","DOI":"10.1001\/jamanetworkopen.2021.20736","article-title":"Congenital Cytomegalovirus Infection Burden and Epidemiologic Risk Factors in Countries with Universal Screening: A Systematic Review and Meta-Analysis","volume":"4","author":"Ssentongo","year":"2021","journal-title":"JAMA Netw. Open"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1001\/jama.289.8.1008","article-title":"Maternal Immunity and Prevention of Congenital Cytomegalovirus Infection","volume":"289","author":"Fowler","year":"2003","journal-title":"JAMA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1093\/cid\/ciac482","article-title":"Prevalence, Outcome, and Prevention of Congenital Cytomegalovirus Infection in Neonates Born to Women with Preconception Immunity (CHILd Study)","volume":"76","author":"Lilleri","year":"2023","journal-title":"Clin. Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1016\/j.ajog.2020.05.038","article-title":"Timing of Primary Maternal Cytomegalovirus Infection and Rates of Vertical Transmission and Fetal Consequences","volume":"223","author":"Chatzakis","year":"2020","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1093\/cid\/ciy1128","article-title":"Sequelae of Congenital Cytomegalovirus Following Maternal Primary Infections Are Limited to Those Acquired in the First Trimester of Pregnancy","volume":"69","author":"Magny","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"100356","DOI":"10.1016\/j.ajogmf.2021.100356","article-title":"Advocating for Cytomegalovirus Maternal Serologic Screening in the First Trimester of Pregnancy: If You Do Not Know Where You Are Going, You Will Wind up Somewhere Else","volume":"3","author":"Ville","year":"2021","journal-title":"Am. J. Obstet. Gynecol. MFM"},{"key":"ref_9","first-page":"100892","article-title":"Consensus Recommendation for Prenatal, Neonatal and Postnatal Management of Congenital Cytomegalovirus Infection from the European Congenital Infection Initiative (ECCI)","volume":"40","author":"Chatzakis","year":"2024","journal-title":"Lancet Reg. Health\u2014Eur."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"9399","DOI":"10.1080\/14767058.2022.2038130","article-title":"Cytomegalovirus DNA Detection in Pregnant Women with a High IgG Avidity Index: A Valuable Tool for Diagnosing Non-Primary Infections?","volume":"35","author":"Karageorgou","year":"2022","journal-title":"J. Matern. Fetal Neonatal Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1093\/infdis\/jir718","article-title":"Immunoglobulin Therapy of Fetal Cytomegalovirus Infection Occurring in the First Half of Pregnancy\u2014A Case-Control Study of the Outcome in Children","volume":"205","author":"Nigro","year":"2012","journal-title":"J. Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2025","DOI":"10.1080\/14767058.2019.1651277","article-title":"Risk of Congenital Cytomegalovirus Infection in Children Born to Women with IgG Avidity in the Grey Zone during First Trimester of Pregnancy","volume":"34","author":"Kekkou","year":"2021","journal-title":"J. Matern. Fetal Neonatal Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1093\/cid\/ciz1030","article-title":"High-Dose Cytomegalovirus (CMV) Hyperimmune Globulin and Maternal CMV DNAemia Independently Predict Infant Outcome in Pregnant Women with a Primary CMV Infection","volume":"71","author":"Nigro","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1056\/NEJMoa043337","article-title":"Passive Immunization during Pregnancy for Congenital Cytomegalovirus Infection","volume":"353","author":"Nigro","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1056\/NEJMoa1310214","article-title":"A Randomized Trial of Hyperimmune Globulin to Prevent Congenital Cytomegalovirus","volume":"370","author":"Revello","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1056\/NEJMoa1913569","article-title":"A Trial of Hyperimmune Globulin to Prevent Congenital Cytomegalovirus Infection","volume":"385","author":"Hughes","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1002\/uog.19164","article-title":"Prevention\u2009of\u2009Maternal-Fetal\u2009Transmission\u2009of Cytomegalovirus after Primary Maternal Infection in the First Trimester by Biweekly Hyperimmunoglobulin Administration","volume":"53","author":"Kagan","year":"2019","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1002\/uog.23596","article-title":"Outcome of Pregnancies with Recent Primary Cytomegalovirus Infection in First Trimester Treated with Hyperimmunoglobulin: Observational Study","volume":"57","author":"Kagan","year":"2021","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Schirwani-Hartl, N., Palmrich, P., Haberl, C., Perkmann-Nagele, N., Kiss, H., Berger, A., Rittenschober-B\u00f6hm, J., Kasprian, G., Kienast, P., and Khalil, A. (2023). Biweekly Versus Monthly Hyperimmune Globulin Therapy for Primary Cytomegalovirus Infection in Pregnancy. J. Clin. Med., 12.","DOI":"10.3390\/jcm12216776"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Vasarri, M.V., Fernicola, F., Arienti, F., Carli, A., Colciago, E., Locatelli, A., Trotta, M., Procopio, A., Zammarchi, L., and Ornaghi, S. (Int. J. Gynaecol. Obstet., 2024). Indirect Impact of SARS-CoV-2 Pandemic on Incidence of Maternal Primary Cytomegalovirus and Toxoplasma Gondii Infection in Pregnancy, Int. J. Gynaecol. Obstet., online ahead of print.","DOI":"10.1002\/ijgo.15534"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"462.e1","DOI":"10.1016\/j.ajog.2016.04.003","article-title":"In Utero Treatment of Congenital Cytomegalovirus Infection with Valacyclovir in a Multicenter, Open-Label, Phase II Study","volume":"215","author":"Ghout","year":"2016","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1093\/cid\/ciac297","article-title":"Describing the Impact of Maternal Hyperimmune Globulin and Valacyclovir on the Outcomes of Cytomegalovirus Infection in Pregnancy: A Systematic Review","volume":"75","author":"Fitzpatrick","year":"2022","journal-title":"Clin. Infect. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1002\/uog.23143","article-title":"Outcome of Fetuses with Congenital Cytomegalovirus Infection and Normal Ultrasound at Diagnosis: Systematic Review and Meta-Analysis","volume":"57","author":"Buca","year":"2021","journal-title":"Ultrasound Obstet. Gynecol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/8\/1241\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:28:40Z","timestamp":1760110120000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/8\/1241"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,2]]},"references-count":23,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["v16081241"],"URL":"https:\/\/doi.org\/10.3390\/v16081241","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,2]]}}}