{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T14:07:53Z","timestamp":1791986873517,"version":"4.4.0"},"reference-count":55,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJNS"],"abstract":"<jats:p>Congenital Cytomegalovirus (cCMV) infection is the leading non-genetic cause of sensorineural hearing loss in newborns. Systematic nationwide screening programmes are lacking. Antiviral valganciclovir therapy could improve auditory outcomes if initiated within the first 30 days of life, making timely diagnosis crucial. To address this, we investigated whether a hearing screening-based protocol is suitable. Between 2015 and 2019, newborns, aged \u226421 days, with repeated abnormal newborn hearing screening (NHS) were prospectively enrolled at University Hospital Frankfurt. Oral mucosal swabs were tested for CMV DNA by real-time PCR, with confirmatory urine and blood diagnostics in positive cases. Of 2741 infants presenting for repeat NHS, 2059 (75.1%) showed normal bilateral findings. Of the 682 (24.9%) with abnormal results, 575 (84.3%) were aged &gt;21 days and thus ineligible. A total of 107 infants (3.9%) met both criteria\u2014abnormal NHS and aged \u226421 days\u2014of whom 100 entered per-protocol analysis. Two (2%) were confirmed as cCMV-positive and received valganciclovir. Among the 48 infants who additionally underwent DBS testing, diagnostic sensitivity and specificity were 100%. The presented NHS-driven cCMV protocol reliably identified cCMV-infected newborns to offer timely antiviral therapy. In the absence of universal cCMV screening, this targeted approach offers a challenging but WHO screening-criteria-compliant strategy to enable timely antiviral intervention.<\/jats:p>","DOI":"10.3390\/ijns12030052","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T17:27:31Z","timestamp":1783531651000},"page":"52","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Hearing Screening-Driven Investigation of Newborns for Congenital Cytomegalovirus Infection at a German University Hospital"],"prefix":"10.3390","volume":"12","author":[{"given":"Niko","family":"Kohmer","sequence":"first","affiliation":[{"name":"Institute of Medical Virology, University Hospital Frankfurt, Goethe-University Frankfurt am Main, 60590 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Mistry","sequence":"additional","affiliation":[{"name":"Princess Margaret Children\u2019s Hospital Darmstadt, 64287 Darmstadt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thorsten","family":"Mosler","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry II, Goethe-University Frankfurt am Main, 60590 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Kramer","sequence":"additional","affiliation":[{"name":"Section of Phoniatrics and Paediatric Audiology, Evangelisches Krankenhaus Oldenburg, Universit\u00e4tsmedizin, 26122 Oldenburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Wei\u00df","sequence":"additional","affiliation":[{"name":"Section of Phoniatrics and Paediatric Audiology, ENT Clinic, University Hospital Frankfurt, Goethe-University Frankfurt am Main, 60590 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfred Lennart","family":"Bissinger","sequence":"additional","affiliation":[{"name":"Institute of Medical Virology and Epidemiology of Viral Diseases, University Hospital T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora","family":"Doberschuetz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Neonatology, Goethe-University Frankfurt am Main, 60590 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Rochwalsky","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Neonatology, Goethe-University Frankfurt am Main, 60590 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger F.","family":"Rabenau","sequence":"additional","affiliation":[{"name":"Institute of Medical Virology, University Hospital Frankfurt, Goethe-University Frankfurt am Main, 60590 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Horst","family":"Buxmann","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Neonatology, Main-Kinzig Clinics Gelnhausen, 63571 Gelnhausen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"424","DOI":"10.3181\/00379727-92-22498","article-title":"Propagation in tissue cultures of a cytopathogenic virus from human salivary gland virus (SGV) disease","volume":"92","author":"Smith","year":"1956","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4","DOI":"10.3181\/00379727-94-22841","article-title":"Isolation of intranuclear inclusion producing agents from infants with illnesses resembling cytomegalic inclusion disease","volume":"94","author":"Craig","year":"1957","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1002\/rmv.544","article-title":"New estimates of the prevalence of neurological and sensory sequelae and mortality associated with congenital cytomegalovirus infection","volume":"17","author":"Dollard","year":"2007","journal-title":"Rev. Med. Virol."},{"key":"ref_4","first-page":"45","article-title":"Primary Human Cytomegalovirus (HCMV) Infection in Pregnancy","volume":"114","author":"Buxmann","year":"2017","journal-title":"Dtsch. Arztebl. Int."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1007\/s10096-020-03814-x","article-title":"Thirty years of CMV seroprevalence\u2014A longitudinal analysis in a German university hospital","volume":"39","author":"Hoehl","year":"2020","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_6","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_7","doi-asserted-by":"crossref","first-page":"1904","DOI":"10.1001\/jama.1986.03380140074025","article-title":"Primary Cytomegalovirus Infection in Pregnancy","volume":"256","author":"Stagno","year":"1986","journal-title":"JAMA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1002\/rmv.535","article-title":"Review and meta-analysis of the epidemiology of congenital cytomegalovirus (CMV) infection","volume":"17","author":"Kenneson","year":"2007","journal-title":"Rev. Med. Virol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1111\/j.1471-0528.2004.00328.x","article-title":"Pre- and periconceptional primary cytomegalovirus infection: Risk of vertical transmission and congenital disease","volume":"112","author":"Daiminger","year":"2005","journal-title":"BJOG"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e11","DOI":"10.1093\/cid\/ciq085","article-title":"Attribution of congenital cytomegalovirus infection to primary versus non-primary maternal infection","volume":"52","author":"Wang","year":"2011","journal-title":"Clin. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"B5","DOI":"10.1016\/j.ajog.2016.02.042","article-title":"Diagnosis and antenatal management of congenital cytomegalovirus infection","volume":"214","author":"Hughes","year":"2016","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e20183095","DOI":"10.1542\/peds.2018-3095","article-title":"Hearing Loss with Congenital Cytomegalovirus Infection","volume":"144","author":"Foulon","year":"2019","journal-title":"Pediatrics"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.jcv.2005.09.016","article-title":"Congenital cytomegalovirus (CMV) infection and hearing deficit","volume":"35","author":"Fowler","year":"2006","journal-title":"J. Clin. Virol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.jpeds.2016.01.024","article-title":"Hearing in Children with Congenital Cytomegalovirus Infection: Results of a Longitudinal Study","volume":"172","author":"Goderis","year":"2016","journal-title":"J. Pediatr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/j.jfluidstructs.2009.04.003","article-title":"Influence of inlet shear on the 3-D flow past a square cylinder at moderate Reynolds number","volume":"25","author":"Lankadasu","year":"2009","journal-title":"J. Fluids Struct."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1097\/INF.0000000000001763","article-title":"Congenital Cytomegalovirus: A European Expert Consensus Statement on Diagnosis and Management","volume":"36","author":"Luck","year":"2017","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e177","DOI":"10.1016\/S1473-3099(17)30143-3","article-title":"Congenital cytomegalovirus infection in pregnancy and the neonate: Consensus recommendations for prevention, diagnosis, and therapy","volume":"17","author":"Rawlinson","year":"2017","journal-title":"Lancet Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/S0022-3476(03)00192-6","article-title":"Effect of ganciclovir therapy on hearing in symptomatic congenital cytomegalovirus disease involving the central nervous system: A randomized, controlled trial","volume":"143","author":"Kimberlin","year":"2003","journal-title":"J. Pediatr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"S22","DOI":"10.1016\/j.jcv.2009.08.012","article-title":"Neurodevelopmental outcomes following ganciclovir therapy in symptomatic congenital cytomegalovirus infections involving the central nervous system","volume":"46","author":"Oliver","year":"2009","journal-title":"J. Clin. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1056\/NEJMoa1404599","article-title":"Valganciclovir for symptomatic congenital cytomegalovirus disease","volume":"372","author":"Kimberlin","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_21","unstructured":"Utah Department of Health and Human Services, and Utah Environmental Public Health Tracking Network Web (2025, November 28). Complete Health Indicator Report of Congenital Cytomegalovirus Infection and Hearing Loss, Available online: https:\/\/ibis.utah.gov\/epht-view\/indicator\/complete_profile\/cCMVHL.html."},{"key":"ref_22","unstructured":"Connecticut Department of Public Health (2025, November 28). Early Hearing Detection and Intervention Program, Available online: https:\/\/portal.ct.gov\/dph\/family-health\/ehdi\/cmv?language=en_US."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"F182","DOI":"10.1136\/archdischild-2012-302230","article-title":"Newborn screening of congenital cytomegalovirus infection using saliva can be influenced by breast feeding","volume":"98","author":"Koyano","year":"2013","journal-title":"Arch. Dis. Child. Fetal Neonatal Ed."},{"key":"ref_24","unstructured":"Bundesausschuss, G. (2026, April 17). Bekanntmachung eines Beschlusses des Gemeinsamen Bundesausschusses \u00fcber eine \u00c4nderung der Kinder-Richtlinien: Einf\u00fchrung eines Neugeborenen-H\u00f6rscreenings. Available online: https:\/\/www.g-ba.de\/downloads\/39-261-681\/2008-06-19-Kinder-H%C3%B6rscreening_BAnz.pdf."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1093\/brain\/94.4.681","article-title":"Auditory-evoked far fields averaged from the scalp of humans","volume":"94","author":"Jewett","year":"1971","journal-title":"Brain"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/S1386-6532(02)00022-7","article-title":"Development and clinical application of a fully controlled quantitative PCR assay for cell-free cytomegalovirus in human plasma","volume":"26","author":"Preiser","year":"2003","journal-title":"J. Clin. Virol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.jcv.2010.04.011","article-title":"Influence of different extraction methods and PCR techniques on the sensitivity of HCMV-DNA detection in dried blood spot (DBS) filter cards","volume":"48","author":"Dietz","year":"2010","journal-title":"J. Clin. Virol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1128\/jcm.21.2.217-221.1985","article-title":"Comparison of standard tube and shell vial cell culture techniques for the detection of cytomegalovirus in clinical specimens","volume":"21","author":"Gleaves","year":"1985","journal-title":"J. Clin. Microbiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1007\/BF00210232","article-title":"Comparison of shell viral culture and serology for the diagnosis of human cytomegalovirus infection in neonates and immunocompromised subjects","volume":"70","author":"Weber","year":"1992","journal-title":"Clin. Investig."},{"key":"ref_30","unstructured":"Virologie, G.F., and Pr\u00e4vention, L. (2026, April 28). Diagnostik und Therapie der CMV-Infektion bei Schwangeren und der Konnatalen CMV-Infektion bei Neugeborenen und Kindern. Available online: https:\/\/register.awmf.org\/de\/leitlinien\/detail\/093-003."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2151","DOI":"10.1056\/NEJMra050700","article-title":"Newborn hearing screening\u2014A silent revolution","volume":"354","author":"Morton","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"100892","DOI":"10.1016\/j.lanepe.2024.100892","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 Eur."},{"key":"ref_33","unstructured":"Wilson, J.M.G., and Jungner, G. (2026, March 24). Principles and Practice of Screening for Disease: WHO Public Health Papers. Available online: https:\/\/iris.who.int\/items\/7a67638b-14e3-4dba-b013-dc206ff279d8."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1086\/528376","article-title":"Pharmacokinetic and pharmacodynamic assessment of oral valganciclovir in the treatment of symptomatic congenital cytomegalovirus disease","volume":"197","author":"Kimberlin","year":"2008","journal-title":"J. Infect. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1001\/jama.2010.423","article-title":"Dried blood spot real-time polymerase chain reaction assays to screen newborns for congenital cytomegalovirus infection","volume":"303","author":"Boppana","year":"2010","journal-title":"JAMA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1056\/NEJMoa1006561","article-title":"Saliva polymerase-chain-reaction assay for cytomegalovirus screening in newborns","volume":"364","author":"Boppana","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1093\/infdis\/jiy057","article-title":"Contribution of Breastfeeding to False-Positive Saliva Polymerase Chain Reaction for Newborn Congenital Cytomegalovirus Screening","volume":"217","author":"Ross","year":"2018","journal-title":"J. Infect. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1136\/archdischild-2015-309154","article-title":"Hearing outcome of infants with congenital cytomegalovirus and hearing impairment","volume":"101","author":"Bilavsky","year":"2016","journal-title":"Arch. Dis. Child."},{"key":"ref_39","unstructured":"World Health Organization (2026, April 17). World Report on Hearing. Available online: https:\/\/iris.who.int\/server\/api\/core\/bitstreams\/5c3fc19f-11c9-4488-af3f-7e636b982aca\/content."},{"key":"ref_40","unstructured":"World Health Organization (2026, April 17). Deafness and Hearing Loss. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/deafness-and-hearing-loss."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.jcv.2007.09.004","article-title":"Congenital cytomegalovirus (CMV) infection as a cause of permanent bilateral hearing loss: A quantitative assessment","volume":"41","author":"Grosse","year":"2008","journal-title":"J. Clin. Virol."},{"key":"ref_42","unstructured":"(2026, June 29). Cochlear Implant International Community of Action, Spend to Save 2025: Investing in Hearing Care for All. Available online: https:\/\/ciicanet.org\/wp-content\/uploads\/2025\/09\/01206_SPEND-TO-SAVE-2025_WEB_9-9-25.pdf."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"ofae311","DOI":"10.1093\/ofid\/ofae311","article-title":"A Geographically Weighted Cost-effectiveness Analysis of Newborn Cytomegalovirus Screening","volume":"11","author":"Lantos","year":"2024","journal-title":"Open Forum Infect. Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1001\/jamapediatrics.2016.2016","article-title":"Cost-effectiveness of Universal and Targeted Newborn Screening for Congenital Cytomegalovirus Infection","volume":"170","author":"Gantt","year":"2016","journal-title":"JAMA Pediatr."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/s00431-024-05953-1","article-title":"Economic evaluation of newborn screening for congenital cytomegalovirus infection: A systematic review","volume":"184","author":"Saito","year":"2025","journal-title":"Eur. J. Pediatr."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1016\/S0140-6736(20)31868-7","article-title":"Valaciclovir to prevent vertical transmission of cytomegalovirus after maternal primary infection during pregnancy: A randomised, double-blind, placebo-controlled trial","volume":"396","author":"Pardo","year":"2020","journal-title":"Lancet"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e20162128","DOI":"10.1542\/peds.2016-2128","article-title":"A Targeted Approach for Congenital Cytomegalovirus Screening Within Newborn Hearing Screening","volume":"139","author":"Fowler","year":"2017","journal-title":"Pediatrics"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/S1473-3099(25)00620-6","article-title":"Lessons derived from a 3-year congenital cytomegalovirus screening programme in Israel: A prospective population-based cohort study","volume":"26","author":"Friedman","year":"2026","journal-title":"Lancet Infect. Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1097\/INF.0b013e31822d9640","article-title":"Congenital cytomegalovirus infection as a cause of sensorineural hearing loss in a highly immune population","volume":"30","author":"Yamamoto","year":"2011","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_50","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_51","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.jpeds.2004.05.041","article-title":"Prevention of child-to-mother transmission of cytomegalovirus among pregnant women","volume":"145","author":"Adler","year":"2004","journal-title":"J. Pediatr."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"S49","DOI":"10.1016\/j.jcv.2009.09.003","article-title":"Does hygiene counseling have an impact on the rate of CMV primary infection during pregnancy? Results of a 3-year prospective study in a French hospital","volume":"46","author":"Picone","year":"2009","journal-title":"J. Clin. Virol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1016\/j.ebiom.2015.08.003","article-title":"Prevention of Primary Cytomegalovirus Infection in Pregnancy","volume":"2","author":"Revello","year":"2015","journal-title":"eBioMedicine"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Tastad, K.J., Schleiss, M.R., Lammert, S.M., and Basta, N.E. (2019). Awareness of congenital cytomegalovirus and acceptance of maternal and newborn screening. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0221725"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.2147\/IJWH.S276214","article-title":"Development and Assessment of a Prenatal Cytomegalovirus (CMV) Educational Survey: Implementation and Impact in a Metropolitan University-Based Clinic","volume":"12","author":"Schaefer","year":"2020","journal-title":"Int. J. Women\u2019s Health"}],"container-title":["International Journal of Neonatal Screening"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2409-515X\/12\/3\/52\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T04:28:27Z","timestamp":1784003307000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2409-515X\/12\/3\/52"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,8]]},"references-count":55,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["ijns12030052"],"URL":"https:\/\/doi.org\/10.3390\/ijns12030052","relation":{},"ISSN":["2409-515X"],"issn-type":[{"value":"2409-515X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,8]]}}}