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Aldè, M.; Binda, S.; Primache, V.; Pellegrinelli, L.; Pariani, E.; Pregliasco, F.; Di Berardino, F.; Cantarella, G.; Ambrosetti, U. Congenital Cytomegalovirus and Hearing Loss. Encyclopedia. Available online: (accessed on 22 June 2024).
Aldè M, Binda S, Primache V, Pellegrinelli L, Pariani E, Pregliasco F, et al. Congenital Cytomegalovirus and Hearing Loss. Encyclopedia. Available at: Accessed June 22, 2024.
Aldè, Mirko, Sandro Binda, Valeria Primache, Laura Pellegrinelli, Elena Pariani, Fabrizio Pregliasco, Federica Di Berardino, Giovanna Cantarella, Umberto Ambrosetti. "Congenital Cytomegalovirus and Hearing Loss" Encyclopedia, (accessed June 22, 2024).
Aldè, M., Binda, S., Primache, V., Pellegrinelli, L., Pariani, E., Pregliasco, F., Di Berardino, F., Cantarella, G., & Ambrosetti, U. (2023, July 24). Congenital Cytomegalovirus and Hearing Loss. In Encyclopedia.
Aldè, Mirko, et al. "Congenital Cytomegalovirus and Hearing Loss." Encyclopedia. Web. 24 July, 2023.
Congenital Cytomegalovirus and Hearing Loss

In developed countries, congenital cytomegalovirus (cCMV) infection is the most common congenital viral infection, representing the leading non-genetic cause of sensorineural hearing loss (HL). Diagnosis of cCMV infection can be performed by detection of CMV DNA in urine or saliva within 2–3 weeks after birth, or later in dried blood samples on the Guthrie card. There are many controversies regarding the preventive, diagnostic, and therapeutic approaches to cCMV infection. HL secondary to cCMV is highly variable in onset, side, degree, audiometric configuration, and threshold changes over time.

congenital cytomegalovirus hearing loss single-sided deafness cochlear implantation vaccine

1. Introduction

Human cytomegalovirus (CMV), also known as human herpesvirus 5 (HHV-5), is a member of the Herpesviridae family and belongs to the Betaherpesvirinae subfamily [1][2]. The Herpesviridae family also includes other eight viruses that primarily infect humans: herpes simplex virus-1 (HHV-1), herpes simplex virus 2 (HHV-2), and varicella zoster virus (HHV-3), belonging to the Alphaherpesvirinae subfamily; Epstein–Barr virus (HHV-4) and Kaposi’s sarcoma-associated herpesvirus (HHV-8), belonging to the Gammaherpesvirinae subfamily; and roseolovirus (HHV-6A, HHV-6B, and HHV-7) belonging to the Betaherpevirinae subfamily [1]. CMV is characterized by a large double-stranded DNA genome and is considered the most complex herpesvirus [2]. The name is derived from the Greek words “cyto”, which means “cell”, and “megalo”, which means “big”. Indeed, CMV causes cyto-nucleomegaly and classic “owl’s eye” inclusions on histology [2]. These peculiar intranuclear inclusions were first detected in 1881 by Ribbert [3], while Goodpasture and Talbot in 1921 were the first to suggest that the “cytomegaly” could be due to a viral agent [4]. Human CMV was first isolated independently by Smith, Rowe, and Weller between 1956 and 1957, while the term “cytomegalovirus” was first proposed in 1960 by Weller [5].
CMV infection is ubiquitous, does not show seasonal variations, and is relatively common among women of reproductive age, with seroprevalence ranging from 45 to 100% [6]. Active CMV infection can result from either primary or non-primary infection. Primary infection occurs when an individual without immunity against CMV becomes infected for the first time, while non-primary infection is due to reinfection with exogenous CMV strains or reactivation of latent endogenous CMV [7]. Indeed, CMV resides latently in cells of the myeloid compartment, including CD34+ hematopoietic progenitor cells and circulating monocytes, and can occasionally reactivate, especially in immunocompromised patients or during critical illness [8]. CMV infection can be transmitted from one individual to another (“horizontal transmission”) through direct contact with body fluids (including saliva, urine, tears, genital secretions, organ transplant, or blood transfusion), or from mother to child (“vertical transmission”) through the placenta (“congenital CMV (cCMV) infection”), delivery, or breast milk (“postnatal CMV infection”) [9][10]. CMV infection is generally asymptomatic or may present as a mononucleosis syndrome in healthy people, while it is potentially life-threatening in immunocompromised patients [9].

2. Current Controversies in Preventive, Diagnostic, and Therapeutic Approaches to Congenital Cytomegalovirus Infection

2.1. Awareness and Knowledge of Congenital Cytomegalovirus Infection

Congenital CMV is a silent global burden that remains largely unrecognized in infants due to the high prevalence of non-specific symptoms or asymptomatic patients [11]. It has been widely demonstrated that women have poor knowledge of cCMV infection compared to other less frequent congenital diseases, such as Down syndrome, toxoplasmosis, and human immunodeficiency virus (HIV) infection [12][13][14]. Given the poor awareness and knowledge of cCMV infection among the world’s population and the lack of targeted prevention strategies, cCMV can be considered “an elephant in our living room” [15]. Providing proper prenatal education aimed at increasing awareness and knowledge of cCMV infection among pregnant women is a need highlighted by studies conducted in several countries, including the United States [16], Canada [17], Japan [13], Australia [18], Saudi Arabia [14], Germany [19], France [20], Switzerland [12], Italy [21], Spain [22], Portugal [23], the United Kingdom [24], and the Republic of Ireland [25]. Moreover, it is crucial to increase awareness of cCMV infection also among the male population and healthcare providers. In particular, men can serve as a vector for maternal infection and should be educated about behaviors that reduce the risk of CMV transmission, such as using condoms during sexual intercourse [21]. Similarly, healthcare professionals should play a key role in raising awareness among pregnant women through the dissemination of appropriate information [26]. However, their knowledge about cCMV is often low, negatively impacting prenatal counseling [22][27]. Indeed, most women are unaware of cCMV or how to reduce the risk of infection during pregnancy, in part due to poor health professionals’ awareness [28]. In this context, it is necessary to promote health campaigns and health education strategies to enhance awareness about cCMV infection [22]. All pregnant women should be adequately advised to avoid certain behavioral practices that increase the risk of CMV infection, such as kissing a child on the lips, sharing utensils, changing diapers, and practicing unsafe sex [10]. As a matter of fact, because no vaccine is currently available and treatment options are limited, the main measures to prevent CMV infection during pregnancy are based on rigorous respect of the hygienic-behavioral rules, such as handwashing after exposure to young children’s body fluids [10][21].

2.2. Maternal Serological Screening for Cytomegalovirus Infection

Diagnosis of primary CMV infection during pregnancy can be made by detection of CMV IgG seroconversion or CMV IgM positivity associated with low IgG avidity [29]. Currently, most public health policies and international scientific societies do not routinely recommend universal maternal prenatal screening for CMV infection due to the following reasons [21][30][31][32]: (a) lack of highly sensitive and specific prenatal tests; (b) CMV serological screening is not applicable to non-primary CMV infection; (c) lack of effective interventions to prevent transmission to the fetus; (d) lack of safe and effective prenatal treatments; (e) inability of laboratory tests to predict which babies will develop long-term neurological and audiological complications; (f) potentially increased rate of unnecessary abortions. Moreover, the false-positive rate would be much higher in the screened population than in women preselected for suspected CMV infection and, as a result, many pregnant women would undergo unnecessary additional testing and invasive procedures [30][33]. Therefore, according to the general agreement, CMV serologic testing should be offered only to pregnant women with symptoms and/or signs suggestive of primary CMV infection (e.g., influenza-like illness and/or fetal abnormalities on prenatal ultrasound examination) [33]. However, most pregnant women want to have CMV serological screening once informed about cCMV infection [34]; some of them make use of the maternal serological screening even if it is not recommended by the national guidelines [19][21][29][35][36]. As a matter of fact, maternal CMV screening followed by targeted neonatal CMV screening (testing neonates whose mothers become seropositive during pregnancy) may help identify asymptomatic cCMV cases in an early stage; Naessens et al. reported that this type of screening allowed the detection of 82% of all cCMV infections [37]. Moreover, women who are aware that they are susceptible to primary CMV infection based on serology are more likely to practice hygiene measures [36]. It is also important to highlight that maternal administration of oral valaciclovir following maternal primary infection in the first trimester of pregnancy has been demonstrated to be effective in reducing the rate of fetal CMV infection [38]. Therefore, maternal CMV screening followed by valaciclovir prevention may prevent most severe cases of cCMV infection [31]. However, possible adverse effects, especially acute renal failure, should be taken into consideration in pregnant women taking valaciclovir. Further studies are needed to investigate the safety and effectiveness of prenatal valaciclovir therapy in pregnancies with maternal CMV infection [39].

2.3. Neonatal Screening for Congenital Cytomegalovirus Infection

Diagnosis of cCMV infection can be performed by detection of CMV DNA in urine or saliva samples within 2–3 weeks after birth, or later by polymerase chain reaction (PCR) assay of dried blood spot (DBS) samples on the Guthrie card, which are universally collected within 3 days from birth [40][41][42]. Targeted cCMV screening through saliva PCR in children who fail the universal newborn hearing screening (UNHS) has been demonstrated to fall within the range between cost-neutral and cost-saving [43]. As a matter of fact, this cCMV screening method is feasible and acceptable to parents, providing the opportunity to start the treatment with oral valganciclovir within the first month of life [43][44]. However, performing cCMV neonatal screening only in babies who fail UNHS would not identify asymptomatic CMV-infected children who will develop late-onset HL [45]. A large study by Fowler et al. has shown that 43% of infants with CMV-related SNHL in the neonatal period and cCMV infants who are at risk of late-onset SNHL were not identified by UNHS [46]. Therefore, new strategies to identify all children with cCMV who remain at risk of late-onset and progressive HL are of paramount importance. In this context, it may be beneficial to extend targeted cCMV screening to children who pass UNHS but are at increased risk of cCMV infection, such as those born SGA or with microencephaly [45]. Indeed, an expanded targeted early cCMV testing program has been shown to improve detection rates of symptomatic cCMV cases, and should be considered as a valid alternative approach to hearing-targeted CMV testing [47]. In particular, cCMV infection should be suspected in all newborns: (a) whose mothers became CMV-seropositive during pregnancy; (b) who have received a confirmed diagnosis of SNHL; (c) who have signs and symptoms suggestive of CMV infection (e.g., SGA, microcephaly, petechiae, thrombocytopenia, unexplained hepatosplenomegaly, idiopathic elevated liver enzymes, and jaundice); (d) who have abnormal neuroimaging consistent with CMV infection (e.g., periventricular calcifications, ventriculomegaly, subependymal pseudocysts, white matter changes, cerebral or cerebellar hypoplasia, and lenticulostriate vasculopathy) [48][49].

2.4. Antiviral Therapy for Congenital Cytomegalovirus Infection

According to the general agreement, treatment with antiviral drugs should be considered only for neonates with severely/moderately symptomatic cCMV infection at birth [48][50]. Intravenous ganciclovir and its orally available prodrug, valganciclovir, are the first-line antiviral agents of choice [51]. Newborns with non-life-threatening disease are generally treated with oral valganciclovir; the recommended dose is 16 mg/kg/dose, administered twice daily for a total of 6 months [52]. Antiviral therapy should be started as soon as a virologic positive result is available, being effective in improving hearing and neurodevelopmental outcomes if started within the first month of life [51]. However, some studies have demonstrated the benefits and safety aspects of treating children with cCMV even beyond the recommended neonatal period [53][54]. Oral valganciclovir appears to have a beneficial role in both preventing and improving SNHL in children with symptomatic cCMV infection [55][56]. Although prolonged valganciclovir treatment for cCMV is generally safe and well-tolerated, a close monitoring of the white blood cell count and hemoglobin levels is mandatory; in particular, severe neutropenia (absolute neutrophil < 500/μL) is a possible adverse effect that can lead to treatment discontinuation [57]. Some retrospective studies have suggested that even children with isolated SNHL due to cCMV may benefit from valganciclovir [21][58][59], but to date no specific clinical trial data are available to support the routine use of antiviral treatment in these patients [60]. However, a study conducted in the United States has shown that the proportion of infants with cCMV treated with valganciclovir has increased markedly in recent years for all disease severity groups, including those without clinical findings [61]. It is crucial to point out that the use of valganciclovir may be associated with many serious adverse effects, such as neutropenia, anemia, thrombocytopenia, hepatotoxicity, and nephrotoxicity [52][57]. Thus, although many experts encourage the use of valganciclovir in infants with isolated HL [48], shared decision-making between pediatricians and parents is extremely important due to the sparse data on benefits and the known risks of treatment [60].

2.5. Vaccines against Congenital Cytomegalovirus Infection

A vaccine against cCMV infection is a major public health priority. Although the development of CMV vaccines began in the 1970s [62][63], no CMV vaccine is available for humans so far [64]. In the year 2000, the National Academy of Medicine of the United States published a document that assigned the human CMV vaccine a high development priority [65]. As a matter of fact, the development of a vaccine capable of conferring effective protection against primary CMV infection may be a valid solution to reduce the serious consequences of intrauterine CMV infection. However, it should be emphasized that a strategy aimed at preventing only primary maternal infection would not address HL and other severe neurological sequelae secondary to cCMV in children born to mothers with pre-existing CMV immunity [66]. Indeed, maternal non-primary CMV infection during pregnancy is considered the greatest burden due to the high seroprevalence of CMV among women of childbearing age [9][21]. Therefore, ideal vaccines should have the ability not only to protect seronegative women from primary infection but also to enhance the immune response in seropositive women to prevent reactivation or reinfection [67]. A viable solution might be a recombinant CMV glycoprotein B vaccine with MF59 adjuvant that appeared to boost both antibody and CD4 T-cell responses in previously CMV-seropositive women, thus raising the possibility to prevent vertical transmission [68]. Unfortunately, CMV vaccines evaluated in clinical trials so far have demonstrated only about 45–50% efficacy against CMV primary infection and none of these have been approved [69][70]. However, a recent mathematical model by Byrne et al. has predicted that even modestly protective CMV vaccination of young children would significantly reduce both CMV transmission to pregnant women and the prevalence of cCMV [71].

3. Hearing Loss Associated with Congenital Cytomegalovirus Infection

The association between cCMV infection and HL was first described in 1964 [72]. Although many studies have been conducted on this important public health issue since then, cCMV infection remains the leading non-genetic cause of SNHL in children in the developed world [51][73][74][75]. Congenital CMV is estimated to be responsible for HL in one in five hearing-impaired children with no other known risk factors [76]. A possible pathogenetic hypothesis is that CMV infection of the marginal cell layer of the stria vascularis may alter potassium and ion circulation, dissipating the endocochlear potential with consequent degeneration of the hair cells of the organ of Corti [77]. Paradoxically, hair cells appear to be spared by CMV infection [76].
The characteristic of HL due to cCMV infection are extremely variable [73][74][75]. First, HL is typically sensorineural and can occur in both symptomatic and asymptomatic children [73][74][75]. Although HL in asymptomatic children (“isolated HL”) is often considered a distinct category, some European experts classify infants with isolated SNHL as having severely symptomatic cCMV [48][60]. SNHL can be present at birth (“congenital HL”) or appear sometime later in life (“delayed-onset HL”) [73][74][75]. A recent systematic review by Vos et al. has reported that the prevalence of HL at birth is over 33% among symptomatic CMV-infected newborns and less than 15% in asymptomatic infections [75]. SNHL presents with later onset in about 10–20% of cCMV cases [49]. The hearing threshold may fluctuate or deteriorate over time [73][74][75]. Fluctuating HL is typically not explained by concurrent middle ear infections and may occur at only a few frequencies [73]. Hearing threshold deterioration can be observed in about half of children with SNHL at birth, regardless of whether they have asymptomatic or symptomatic infection [73]. However, in children with symptomatic CMV infection, HL is generally more severe and tends to progress earlier [49][73]. It is important to underline that a diagnosis of cCMV does not exclude the coexistence of other disorders that might explain hearing deterioration, such as genetic syndromes, specific mutations in genes associated with isolated HL, or ear malformations [21]. According to Peterson et al., the sub-cohort of CMV-positive newborns with symmetric mild-to-moderate bilateral HL will have at least a 7% chance of having pathogenic gene variants associated with HL [78]. Therefore, children with bilateral symmetric SNHL should undergo comprehensive genetic testing, regardless of cCMV status [78].


  1. Davison, A.J. Herpesvirus systematics. Vet. Microbiol. 2010, 143, 52–69.
  2. Louten, J. Essential Human Virology, 2nd ed.; Elsevier: Amsterdam, The Netherlands, 2022; p. 264.
  3. Ribbert, D. Uber protozoenartige zellen in der niere eines syphilitischen neugoborenen und in der parotis von kindern. Zentralbl. Allg. Pathol. 1904, 15, 945–948.
  4. Goodpasture, E.W.; Talbot, F.B. Concerning the nature of “proteozoan-like” cells in certain lesions of infancy. Am. J. Dis. Child. 1921, 21, 415–421.
  5. Riley, H.D., Jr. History of the cytomegalovirus. South. Med. J. 1997, 90, 184–190.
  6. Cannon, M.J.; Schmid, D.S.; Hyde, T.B. Review of cytomegalovirus seroprevalence and demographic characteristics associated with infection. Rev. Med. Virol. 2010, 20, 202–213.
  7. Griffiths, P.; Reeves, M. Pathogenesis of human cytomegalovirus in the immunocompromised host. Nat. Rev. Microbiol. 2021, 19, 759–773.
  8. Smith, N.A.; Chan, G.C.; O’Connor, C.M. Modulation of host cell signaling during cytomegalovirus latency and reactivation. Virol. J. 2021, 18, 207.
  9. Gupta, M.; Shorman, M. Cytomegalovirus. In StatPearls; StatPearls Publishing: Treasure Island, FL, USA, 2022.
  10. Pass, R.F.; Anderson, B. Mother-to-Child Transmission of Cytomegalovirus and Prevention of Congenital Infection. J. Pediatr. Infect. Dis. Soc. 2014, 3 (Suppl. 1), S2–S6.
  11. Manicklal, S.; Emery, V.C.; Lazzarotto, T.; Boppana, S.B.; Gupta, R.K. The “silent” global burden of congenital cytomegalovirus. Clin. Microbiol. Rev. 2013, 26, 86–102.
  12. Willame, A.; Blanchard-Rohner, G.; Combescure, C.; Irion, O.; Posfay-Barbe, K.; Martinez de Tejada, B. Awareness of Cytomegalovirus Infection among Pregnant Women in Geneva, Switzerland: A Cross-sectional Study. Int. J. Environ. Res. Public Health 2015, 12, 15285–15297.
  13. Kobayashi, M.; Okahashi, A.; Okuyama, K.; Hiraishi, N.; Morioka, I. Awareness and knowledge of congenital cytomegalovirus infection among pregnant women and the general public: A web-based survey in Japan. Environ. Health Prev. Med. 2021, 26, 117.
  14. Almishaal, A.A. Knowledge of cytomegalovirus infection among women in Saudi Arabia: A cross-sectional study. PLoS ONE 2022, 17, e0274863.
  15. Demmler-Harrison, G.J. Congenital Cytomegalovirus Infection: The Elephant in Our Living Room. JAMA Pediatr. 2016, 170, 1142–1144.
  16. Tastad, K.J.; Schleiss, M.R.; Lammert, S.M.; Basta, N.E. Awareness of congenital cytomegalovirus and acceptance of maternal and newborn screening. PLoS ONE 2019, 14, e0221725.
  17. Wizman, S.; Lamarre, V.; Coic, L.; Kakkar, F.; Le Meur, J.B.; Rousseau, C.; Boucher, M.; Tapiero, B. Awareness of cytomegalovirus and risk factors for susceptibility among pregnant women, in Montreal, Canada. BMC Pregnancy Childbirth 2016, 16, 54.
  18. Lazzaro, A.; Vo, M.L.; Zeltzer, J.; Rawlinson, W.; Nassar, N.; Daly, K.; Lainchbury, A.; Shand, A. Knowledge of congenital cytomegalovirus (CMV) in pregnant women in Australia is low, and improved with education. Aust. N. Z. J. Obstet. Gynaecol. 2019, 59, 843–849.
  19. Greye, H.; Henning, S.; Freese, K.; Köhn, A.; Lux, A.; Radusch, A.; Redlich, A.; Schleef, D.; Seeger, S.; Thäle, V.; et al. Cross-sectional study to assess awareness of cytomegalovirus infection among pregnant women in Germany. BMC Pregnancy Childbirth 2022, 22, 964.
  20. Alain, S.; Garnier-Geoffroy, F.; Labrunie, A.; Montané, A.; Marin, B.; Gatet, M.; Grosjean, J.; Dufour, V.; Saugeras, M.; Postil, D.; et al. Cytomegalovirus (CMV) Shedding in French Day-Care Centers: A Nationwide Study of Epidemiology, Risk Factors, Centers’ Practices, and Parents’ Awareness of CMV. J. Pediatr. Infect. Dis. Soc. 2020, 9, 686–694.
  21. Aldè, M.; Caputo, E.; Di Berardino, F.; Ambrosetti, U.; Barozzi, S.; Piatti, G.; Zanetti, D.; Pignataro, L.; Cantarella, G. Hearing outcomes in children with congenital cytomegalovirus infection: From management controversies to lack of parents’ knowledge. Int. J. Pediatr. Otorhinolaryngol. 2023, 164, 111420.
  22. Castillo, K.; Hawkins-Villarreal, A.; Valdés-Bango, M.; Guirado, L.; Scazzocchio, E.; Porta, O.; Falguera, G.; López, M.; Palacio, M.; Gratacós, E.; et al. Congenital Cytomegalovirus Awareness and Knowledge among Health Professionals and Pregnant Women: An Action towards Prevention. Fetal Diagn. Ther. 2022, 49, 265–272.
  23. Monteiro, S.; Gonçalves, A.; Torrão, M.M.; Costa, V.; Almeida, A. Knowledge of cytomegalovirus and available prevention strategies in pregnancy: A cross-sectional study in Portugal. J. Matern.-Fetal Neonatal Med. 2023, 36, 2183754.
  24. Calvert, A.; Vandrevala, T.; Parsons, R.; Barber, V.; Book, A.; Book, G.; Carrington, D.; Greening, V.; Griffiths, P.; Hake, D.; et al. Changing knowledge, attitudes and behaviours towards cytomegalovirus in pregnancy through film-based antenatal education: A feasibility randomised controlled trial of a digital educational intervention. BMC Pregnancy Childbirth 2021, 21, 565.
  25. Basit, I.; Crowley, D.; Geary, M.; Kirkham, C.; Mc Dermott, R.; Cafferkey, M.; Sayers, G. Awareness and Preventative Behaviours Regarding Toxoplasma, Listeria and Cytomegalovirus Among Pregnant Women. Ir. Med. J. 2019, 112, 947.
  26. Benou, S.; Dimitriou, G.; Papaevangelou, V.; Gkentzi, D. Congenital cytomegalovirus infection: Do pregnant women and healthcare providers know enough? A systematic review. J. Matern.-Fetal Neonatal Med. 2022, 35, 6566–6575.
  27. Pesch, M.H.; Anderson, C.; Mowers, E. Improving Obstetric Provider Congenital Cytomegalovirus Knowledge and Practices. Infect. Dis. Obstet. Gynecol. 2020, 2020, 8875494.
  28. Midgley, G.; Smithers-Sheedy, H.; McIntyre, S.; Badawi, N.; Keogh, J.; Jones, C.A. Congenital Cytomegalovirus Prevention, Awareness and Policy Recommendations—A Scoping Study. Infect. Disord. Drug Targets 2020, 20, 291–302.
  29. Shimada, K.; Toriyabe, K.; Kitamura, A.; Morikawa, F.; Minematsu, T.; Ikejiri, M.; Suga, S.; Toyoda, H.; Amano, K.; Kitano, M.; et al. Primary cytomegalovirus infection during pregnancy and congenital infection: A population-based, mother-child, prospective cohort study. J. Perinatol. 2021, 41, 2474–2481.
  30. Lazzarotto, T.; Blázquez-Gamero, D.; Delforge, M.L.; Foulon, I.; Luck, S.; Modrow, S.; Leruez-Ville, M. Congenital Cytomegalovirus Infection: A Narrative Review of the Issues in Screening and Management From a Panel of European Experts. Front. Pediatr. 2020, 8, 13.
  31. Seror, V.; Leruez-Ville, M.; Ӧzek, A.; Ville, Y. Leaning towards Cytomegalovirus serological screening in pregnancy to prevent congenital infection: A cost-effectiveness perspective. BJOG 2022, 129, 301–312.
  32. Iijima, S. Pitfalls in the Serological Evaluation of Maternal Cytomegalovirus Infection as a Potential Cause of Fetal and Neonatal Involvements: A Narrative Literature Review. J. Clin. Med. 2022, 11, 5006.
  33. Pass, R.F.; Arav-Boger, R. Maternal and fetal cytomegalovirus infection: Diagnosis, management, and prevention. F1000Research 2018, 7, 255.
  34. Beaudoin, M.L.; Renaud, C.; Boucher, M.; Kakkar, F.; Gantt, S.; Boucoiran, I. Perspectives of women on screening and prevention of CMV in pregnancy. Eur. J. Obstet. Gynecol. Reprod. Biol. 2021, 258, 409–413.
  35. Rubinacci, V.; Fumagalli, M.; Meraviglia, G.; Gianolio, L.; Sala, A.; Stracuzzi, M.; Dighera, A.; Zuccotti, G.V.; Giacomet, V. Congenital CMV, Lights and Shadows on Its Management: The Experience of a Reference Center in Northern Italy. Children 2022, 9, 655.
  36. Rudd, I.P.; Marzan, M.B.; Hui, L. Cytomegalovirus serological screening at the first antenatal visit: A tertiary-centre audit of general practitioner practices and maternal seroprevalence. Aust. N. Z. J. Obstet. Gynaecol. 2023, 63, 454–459.
  37. Naessens, A.; Casteels, A.; Decatte, L.; Foulon, W. A serologic strategy for detecting neonates at risk for congenital cytomegalovirus infection. J. Pediatr. 2005, 146, 194–197.
  38. Shahar-Nissan, K.; Pardo, J.; Peled, O.; Krause, I.; Bilavsky, E.; Wiznitzer, A.; Hadar, E.; Amir, J. Valaciclovir to prevent vertical transmission of cytomegalovirus after maternal primary infection during pregnancy: A randomised, double-blind, placebo-controlled trial. Lancet 2020, 396, 779–785.
  39. D’Antonio, F.; Marinceu, D.; Prasad, S.; Khalil, A. Effectiveness and safety of prenatal valacyclovir for congenital cytomegalovirus infection: Systematic review and meta-analysis. Ultrasound Obstet. Gynecol. 2023, 61, 436–444.
  40. Binda, S.; Caroppo, S.; Didò, P.; Primache, V.; Veronesi, L.; Calvario, A.; Piana, A.; Barbi, M. Modification of CMV DNA detection from dried blood spots for diagnosing congenital CMV infection. J. Clin. Virol. 2004, 30, 276–279.
  41. Meyer, L.; Sharon, B.; Huang, T.C.; Meyer, L.; Sharon, B.; Huang, T.C.; Meyer, A.C.; Gravel, K.E.; Schimmenti, L.A.; Swanson, E.C.; et al. Analysis of archived newborn dried blood spots (DBS) identifies congenital cytomegalovirus as a major cause of unexplained pediatric sensorineural hearing loss. Am. J. Otolaryngol. 2017, 38, 565–570.
  42. Pellegrinelli, L.; Galli, C.; Primache, V.; Alde’, M.; Fagnani, E.; Di Berardino, F.; Zanetti, D.; Pariani, E.; Ambrosetti, U.; Binda, S. Diagnosis of congenital CMV infection via DBS samples testing and neonatal hearing screening: An observational study in Italy. BMC Infect. Dis. 2019, 19, 652.
  43. Gillespie, A.N.; Dalziel, K.; Webb, E.; Wong, J.; Jones, C.A.; Sung, V.; HearS-cCMV Project. Targeted screening for congenital cytomegalovirus: A micro-costing analysis. J. Paediatr. Child Health 2023, 59, 64–71.
  44. Fourgeaud, J.; Boithias, C.; Walter-Nicolet, E.; Kermorvant, E.; Couderc, S.; Parat, S.; Pol, C.; Mousset, C.; Bussières, L.; Guilleminot, T.; et al. Performance of Targeted Congenital Cytomegalovirus Screening in Newborns Failing Universal Hearing Screening: A Multicenter Study. Pediatr. Infect. Dis. J. 2022, 41, 478–481.
  45. Aldè, M.; Ambrosetti, U. Letter to the Editor. J. Paediatr. Child Health 2023, 59, 776.
  46. Fowler, K.B.; McCollister, F.P.; Sabo, D.L.; Shoup, A.G.; Owen, K.E.; Woodruff, J.L.; Cox, E.; Mohamed, L.S.; Choo, D.I.; Boppana, S.B.; et al. A Targeted Approach for Congenital Cytomegalovirus Screening within Newborn Hearing Screening. Pediatrics 2017, 139, e20162128.
  47. Suarez, D.; Nielson, C.; McVicar, S.B.; Sidesinger, M.; Ostrander, B.; O’Brien, E.; Ampofo, K.; Ling, C.Y.; Miner, L.J.; Park, A.H. Analysis of an Expanded Targeted Early Cytomegalovirus Testing Program. Otolaryngol. Head Neck Surg. 2023. online ahead of print.
  48. Luck, S.E.; Wieringa, J.W.; Blázquez-Gamero, D.; Henneke, P.; Schuster, K.; Butler, K.; Capretti, M.G.; Cilleruelo, M.J.; Curtis, N.; Garofoli, F.; et al. Congenital Cytomegalovirus: A European Expert Consensus Statement on Diagnosis and Management. Pediatr. Infect. Dis. J. 2017, 36, 1205–1213.
  49. Kettler, M.; Shoup, A.; Moats, S.; Steuerwald, W.; Jones, S.; Stiell, S.C.; Chappetto, J. American Academy of Audiology Position Statement on Early Identification of Cytomegalovirus in Newborns. J. Am. Acad. Audiol. 2023. online ahead of print.
  50. Rawlinson, W.D.; Boppana, S.B.; Fowler, K.B.; Kimberlin, D.W.; Lazzarotto, T.; Alain, S.; Daly, K.; Doutré, S.; Gibson, L.; Giles, M.L.; et al. Congenital cytomegalovirus infection in pregnancy and the neonate: Consensus recommendations for prevention, diagnosis, and therapy. Lancet Infect. Dis. 2017, 17, e177–e188.
  51. Marsico, C.; Kimberlin, D.W. Congenital Cytomegalovirus infection: Advances and challenges in diagnosis, prevention and treatment. Ital. J. Pediatr. 2017, 43, 38.
  52. Kimberlin, D.W.; Jester, P.M.; Sánchez, P.J.; Ahmed, A.; Arav-Boger, R.; Michaels, M.G.; Ashouri, N.; Englund, J.A.; Estrada, B.; Jacobs, R.F.; et al. Valganciclovir for symptomatic congenital cytomegalovirus disease. N. Engl. J. Med. 2015, 372, 933–943.
  53. Dorfman, L.; Amir, J.; Attias, J.; Bilavsky, E. Treatment of congenital cytomegalovirus beyond the neonatal period: An observational study. Eur. J. Pediatr. 2020, 179, 807–812.
  54. Morioka, I.; Kakei, Y.; Omori, T.; Nozu, K.; Fujioka, K.; Takahashi, N.; Yoshikawa, T.; Moriuchi, H.; Ito, Y.; Oka, A.; et al. Oral Valganciclovir Therapy in Infants Aged ≤2 Months with Congenital Cytomegalovirus Disease: A Multicenter, Single-Arm, Open-Label Clinical Trial in Japan. J. Clin. Med. 2022, 11, 3582.
  55. Bilavsky, E.; Shahar-Nissan, K.; Pardo, J.; Attias, J.; Amir, J. Hearing outcome of infants with congenital cytomegalovirus and hearing impairment. Arch. Dis. Child. 2016, 101, 433–438.
  56. Suganuma, E.; Sakata, H.; Adachi, N.; Asanuma, S.; Furuichi, M.; Uejima, Y.; Sato, S.; Abe, T.; Matsumoto, D.; Takahashi, R.; et al. Efficacy, safety, and pharmacokinetics of oral valganciclovir in patients with congenital cytomegalovirus infection. J. Infect. Chemother. 2021, 27, 185–191.
  57. Ziv, L.; Yacobovich, J.; Pardo, J.; Yarden-Bilavsky, H.; Amir, J.; Osovsky, M.; Bilavsky, E. Hematologic Adverse Events Associated with Prolonged Valganciclovir Treatment in Congenital Cytomegalovirus Infection. Pediatr. Infect. Dis. J. 2019, 38, 127–130.
  58. Yilmaz Çiftdogan, D.; Vardar, F. Effect on hearing of oral valganciclovir for asymptomatic congenital cytomegalovirus infection. J. Trop. Pediatr. 2011, 57, 132–134.
  59. Pasternak, Y.; Ziv, L.; Attias, J.; Amir, J.; Bilavsky, E. Valganciclovir Is Beneficial in Children with Congenital Cytomegalovirus and Isolated Hearing Loss. J. Pediatr. 2018, 199, 166–170.
  60. Lanzieri, T.M.; Pesch, M.H.; Grosse, S.D. Considering Antiviral Treatment to Preserve Hearing in Congenital CMV. Pediatrics 2023, 151, e2022059895.
  61. Leung, J.; Grosse, S.D.; Hong, K.; Pesch, M.H.; Lanzieri, T.M. Changes in Valganciclovir Use Among Infants with Congenital Cytomegalovirus Diagnosis in the United States, 2009–2015 and 2016–2019. J. Pediatr. 2022, 246, 274–278.e2.
  62. Elek, S.D.; Stern, H. Development of a vaccine against mental retardation caused by cytomegalovirus infection in utero. Lancet 1974, 1, 1–5.
  63. Plotkin SA, Furukawa T, Zygraich N, Huygelen Candidate cytomegalovirus strain for human vaccination. Infect. Immun. 1975, 12, 521–527.
  64. Plotkin, S.A. Can We Prevent Congenital Infection by Cytomegalovirus? Clin. Infect. Dis. 2023, 76, 1705–1707.
  65. Institute of Medicine Committee to Study Priorities for Vaccine, D. The national academies collection: Reports funded by national institutes of health. In Vaccines for the 21st Century: A Tool for Decision Making; Stratton, K.R., Durch, J.S., Lawrence, R.S., Eds.; National Academies Press (US): Washington, DC, USA, 2000.
  66. Sartori, P.; Egloff, C.; Hcini, N.; Vauloup Fellous, C.; Périllaud-Dubois, C.; Picone, O.; Pomar, L. Primary, Secondary, and Tertiary Prevention of Congenital Cytomegalovirus Infection. Viruses 2023, 15, 819.
  67. Chiopris, G.; Veronese, P.; Cusenza, F.; Procaccianti, M.; Perrone, S.; Daccò, V.; Colombo, C.; Esposito, S. Congenital Cytomegalovirus Infection: Update on Diagnosis and Treatment. Microorganisms 2020, 8, 1516.
  68. Sabbaj, S.; Pass, R.F.; Goepfert, P.A.; Pichon, S. Glycoprotein B vaccine is capable of boosting both antibody and CD4 T-cell responses to cytomegalovirus in chronically infected women. J. Infect. Dis. 2011, 203, 1534–1541.
  69. Pass, R.F.; Zhang, C.; Evans, A.; Simpson, T.; Andrews, W.; Huang, M.L.; Corey, L.; Hill, J.; Davis, E.; Flanigan, C.; et al. Vaccine prevention of maternal cytomegalovirus infection. N. Engl. J. Med. 2009, 360, 1191–1199.
  70. Bernstein, D.I.; Munoz, F.M.; Callahan, S.T.; Rupp, R.; Wootton, S.H.; Edwards, K.M.; Turley, C.B.; Stanberry, L.R.; Patel, S.M.; Mcneal, M.M.; et al. Safety and efficacy of a cytomegalovirus glycoprotein B (gB) vaccine in adolescent girls: A randomized clinical trial. Vaccine 2016, 34, 313–319.
  71. Byrne, C.; Coombs, D.; Gantt, S. Modestly protective cytomegalovirus vaccination of young children effectively prevents congenital infection at the population level. Vaccine 2022, 40, 5179–5188.
  72. Medearis, D.N., Jr. Viral infections during pregnancy and abnormal human development. Am. J. Obstet. Gynecol. 1964, 90, 1140–1148.
  73. Fowler, K.B. Congenital cytomegalovirus infection: Audiologic outcome. Clin. Infect. Dis. 2013, 57 (Suppl. 4), S182–S184.
  74. Goderis, J.; De Leenheer, E.; Smets, K.; Van Hoecke, H.; Keymeulen, A.; Dhooge, I. Hearing loss and congenital CMV infection: A systematic review. Pediatrics 2014, 134, 972–982.
  75. Vos, B.; Noll, D.; Whittingham, J.; Pigeon, M.; Bagatto, M.; Fitzpatrick, E.M. Cytomegalovirus-A Risk Factor for Childhood Hearing Loss: A Systematic Review. Ear Hear. 2021, 42, 1447–1461.
  76. Teissier, N.; Bernard, S.; Quesnel, S.; Van Den Abbeele, T. Audiovestibular consequences of congenital cytomegalovirus infection. Eur. Ann. Otorhinolaryngol. Head Neck Dis. 2016, 133, 413–418.
  77. Gabrielli, L.; Bonasoni, M.P.; Santini, D.; Piccirilli, G.; Chiereghin, A.; Guerra, B.; Landini, M.P.; Capretti, M.G.; Lanari, M.; Lazzarotto, T. Human fetal inner ear involvement in congenital cytomegalovirus infection. Acta Neuropathol. Commun. 2013, 1, 63.
  78. Peterson, J.; Nishimura, C.; Smith, R.J.H. Genetic Testing for Congenital Bilateral Hearing Loss in the Context of Targeted Cytomegalovirus Screening. Laryngoscope 2020, 130, 2714–2718.
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