A systematic literature review of the economic and healthcare resource burden of cytomegalovirus

Figures & data

Figure 1. PRISMA flow diagram of the screening process and study selection for the assessment of the economic impact of CMV.

Table 1. Summary of included studies (n = 24) reporting direct healthcare costs/charges, resource utilization and indirect costs related to CMV or cCMV.

Reference	Type of analysis/outcome	Disease/case type	Study design/methods	Study period	Study population and comparators	Top-line results
United States
Meyers et al.^18	Direct healthcare costs Resource utilization (hospitalization)	cCMV	Retrospective claims database analysis with matched control cohort	2011–2016	Birth analysis of infants with symptomatic cCMV (n = 397 [vaginal delivery (n = 167), cesarean delivery (n = 230]) and matched controls.	Mean difference in total healthcare costs in the first year of life for infants with versus without cCMV infection was $58,806 cCMV infection was associated with ∼70% and ∼32% increase in length of hospital stay among newborns with vaginal and cesarean delivery, respectively
Inagaki et al.^19	Healthcare charges Resource utilization (hospitalization)	cCMV	Retrospective analysis of serial cross-sectional data by birth year	2000–2012	Infants with symptomatic cCMV (n = 1349) by birth year: 2000 (n = 221), 2003 (n = 222), 2006 (n = 235), 2009 (n = 327), 2012 (n = 344)	Total charges per case for infants with cCMV infection were $45,771 for those born in 2000 and $86,514 for those born in 2012 Median duration of hospital stay for infants with cCMV infection was similar in 2000 (15 days) and in 2012 (18 days), and longer than for infants without cCMV infection (2 days)
Grossberg et al.^20	Healthcare charges Resource utilization (hospitalization)	CMV and UC	Retrospective database analysis	2006–2012	Adults aged 18–85 with both UC and CMV (n = 145) or with UC and no CMV (n = 32,290)	Mean length of hospital stay for patients with UC and CMV infection was longer (16.31 days) versus that for patients with UC and no CMV infection (5.52 days) Mean total hospital charges for patients with UC and CMV infection were higher ($111,835.50) versus that for patients with UC and no CMV infection ($39,895.50)
Lucas et al.^21	Direct healthcare costs Indirect costs	cCMV	Conceptual framework based on literature review and validation Analysis of direct, indirect, and intangible costs	2019	cCMV with vs without disability, developmental delay, or impairment in three life stages namely, infants, children and adolescents, and adults	Costs varied depending on the life stage, diagnosis, and the type and degree of developmental disability
Lanzieri et al.^22	Resource utilization (hospitalization)	cCMV or CMV	Retrospective database analysis of prevalence and clinical characteristics of infants	2005–2010	Infants in NICU with cCMV/CMV infection (VLBW [n = 87] and birthweight >1500 g [n = 69]) Infants in NICU without cCMV/CMV (VLBW (n = 33,424) or birthweight >1500 g (n = 57,614)	Median length of hospital stay was longer for surviving VLBW (<1500 g) infants with cCMV/CMV infection (99 days) versus those without (60 days) Median length of hospital stay was longer for surviving infants with birthweight >1500 g with cCMV/CMV infection (48 days) versus those without (14 days)
Tran et al.^23	Resource utilization (hospitalization)	cCMV or CMV	Retrospective database analysis	2005–2016	Infants in NICU with cCMV/CMV (VLBW [n = 174] or birthweight [>1500 g; n = 145]) Infants in NICU without cCMV/CMV (VLBW [n = 64,101] or birthweight >1500 g [n = 116,416])	Median length of hospital stay was longer for VLBW (<1500 g) infants with cCMV/CMV infection (98 days) versus those without (46 days) Median length of hospital stay was longer infants with birthweight >1500 g with cCMV/CMV infection (98 days) versus those without (14 days)
The Netherlands
Korndewal et al.^24	Direct healthcare costs Resource utilization (hospitalization)	cCMV	Retrospective cohort study	2012–2013	Children with cCMV (n = 133) and without cCMV (n = 274)	Total healthcare costs in the first six years of life amount to €6113 per child with cCMV and €3546 per child without cCMV Mean total costs per child related to long-term impairments, such as hearing loss were €17,205 for children with cCMV and €8332 for children without cCMV
United Kingdom
Retzler et al.^25	Direct healthcare costs Indirect (nonmedical) costs	cCMV	Static cost model	2016	Individuals of all ages with cCMV	Estimated mean total costs of cCMV infection: ₤732 million Approximately 40% of total cost from direct costs incurred by the government for health, social, and educational services with the remaining 60% attributed to indirect costs, including loss of productivity to society
Ahmed et al.^26	Resource utilization (hospitalization, colectomy rates)	cCMV	Retrospective chart review of from the authors’ institution from 2005 to 2011	2005–2011	Adult patients with IBD and a diagnosis of CMV infection (n = 35)	Six of 11 patients with IBD and CMV colitis experienced a recurrence of symptoms within 4 weeks of stopping a 1-week course of IV ganciclovir treatment and were readmitted to the hospital; 16 patients treated with a 2-week course of IV ganciclovir showed more favorable outcomes including a shortened length of hospital stay than patients treated with a 1-week course of IV ganciclovir or a 2-week course of oral valganciclovir
Germany
Walter et al.^17	Resource utilization Direct healthcare costs Indirect costs	cCMV	Incidence-based, cost of illness model	2008	Children with cCMV (n = 1431); grouped by the presence or absence of symptoms at birth and by whether or not they experienced remote damages	Total direct costs for children with symptomatic cCMV infection at birth were €68,379 and €99,613 per child with and without remote damages, respectively 92% of total costs related to cCMV in Germany are indirect costs
France
Delvincourt et al.^27	Resource utilization (length of hospital stay, colectomy rates; drug use)	CMV	Case-control and retrospective analyses evaluating consequences of latent CMV infection reactivation in flaring IBD patients	2003–2012	CMV-positive (+) UC patients (n = 26) and matched controls; IBD patients with CMV reactivation (n = 105 including 80 with positive blood PCR receiving antiviral treatment (n = 49) or not receiving antiviral treatment (n = 31)	There was no significant difference in the length of hospital stay between CMV + and CMV-negative patients with IBD (8.7 vs. 9.7 days) and 3-month colectomy rates (15.4% vs. 23.1 %). The mean length of hospital stay was longer for patients with CMV + who received antivirals than those who did not (16.3 days versus 8.3 days), suggesting higher severity in the treated population
Touhami et al.^28	Resource utilization (% of patients receiving surgery; drug utilization)	CMV	Retrospective chart review of the treatment of patients with CMV AU	2005–2015	Overall study population (n = 35); CMV AU patients (n = 35; with PSS [n = 24] or chronic non-specific AU [n = 11])	Glaucoma or phacoemulsification surgery was performed in 25.7% and 31.4% of all CMV patients, 20.8% and 25.0% of CMV patients with PSS, and 36.3% and 45.5%% of CMV patients with chronic AU, respectively
Slovenia
Saletinger et al.^29	Resource utilization (hospitalization and treatment with oxygen)	CMV	Prospective analysis reporting length of hospital stay and treatment with oxygen for patients with reactivated CMV versus patients without CMV reactivation	2011–2013	Adult patients with community-acquired pneumonia (n = 80): CMV DNA positive (n = 6); CMV DNA negative (n = 74)	Among immunocompetent adult patients with community-acquired pneumonia, not treated in ICU, there was no significant difference in median length of hospital stay between those who tested positive for CMV DNA versus those who tested negative for CMV DNA (12 days versus 10 days, respectively)
Spain
Vergara et al.^30	Resource utilization (hospitalization/ICU)	CMV	Prospective analysis of length of stays in the hospital and ICU (days) for adult patients with CMV infection	2013–2015	ICU patients with CMV as detected by bronchioalveolar lavage: CMV positive (n = 35) CMV negative (n = 98)	Length of hospital and ICU stays were longer for ICU patients with CMV infection (46 and 31.5 days, respectively) than those without (35 and 19.5, respectively)
Poland
Jedlińska-Pijanowska et al.^31	Resource utilization (hospitalization)	cCMV	Retrospective study	2012–2017	Infants with symptomatic cCMV treated with ganciclovir-based antiviral therapy (n = 60) or oral VGCV-based therapy (n = 38)	Mean length of hospitalization depended on the type of antiviral therapy administered. In 2012, the mean length of hospital stay was 38, 28, and 6 days for ganciclovir monotherapy, sequential ganciclovir plus VGCV, and oral VGCV monotherapy, respectively. In 2017, the mean length of hospital stay was 29 and 9 days for sequential and VGCV therapy, respectively
Italy
Maconi et al.^32	Resource utilization (length of hospital stay, colectomy rates)	CMV	Retrospective database analysis included data on antiviral treatments, lengths of hospital stay, and colectomy rates	1998–2012	Active IBD patients with CMV (n = 38); patients who received antiviral treatment (n = 13) and patients who did not receive antiviral treatment (n = 25)	In a cohort of 38 patients with IBD flare and CMV infection, the average length of stay was 14 days (range: 7–35 days); hospital stay duration was comparable between treated and untreated patients
Japan
Aoki et al.^33	Direct healthcare costs Indirect costs	cCMV	Literature-based model of economic and lifetime health burdens of cCMV infection in Japan based on annual birth cohort in 2019 using demographic, epidemiologic, health value, and economic indicators	2019	2019 Japanese birth cohort	The impact of cCMV infection for the Japanese 2019 birth cohort was approximately ¥27.6 billion, of which 4% comprised direct healthcare costs/charges
Maeda et al.^34	Total costs of hospitalization Resource utilization (hospitalization)	CMV	Retrospective database analysis reporting on the impact of opportunistic infections on in-hospital mortality, lengths of hospital stay, and total costs	2007–2010	Adults with T-cell leukemia and CMV as an opportunistic infection (n = 109)	Among adult patients with T-cell leukemia between 2007–2010, median total charges associated with CMV infections were $20,549 per instance
Lin et al.^35	Resource utilization (% of admissions to NICU)	cCMV	Longitudinal observational analysis using claims data, reporting incidence of adverse CMV sequelae in cCMV patients	2010–2017	Overall study population (n = 207,547); Infants with cCMV (n = 53); Infants with cCMV and related symptoms (n = 36); Individuals with cCMV without related symptoms (n = 17)	Overall, 47% of patients with cCMV infection were admitted to the neonatal ICU compared with 18% of infants without symptoms of cCMV infection at birth; however, these differences did not reach statistical significance
Brazil
Niz Xavier et al.^36	Resource utilization (% of newborns receiving mechanical ventilation)	cCMV	Cross-sectional analysis on the frequency of cCMV infection in newborns admitted to the NICU	2010–2012	Overall study population (n = 520); Newborns who tested positive for cCMV (n = 13)	23% (n = 3/13) of newborns who tested positive for cCMV received mechanical ventilation
Yamamoto et al.^37	Resource utilization (OAE and ABR examinations)	cCMV	Prospective analysis of SNHL in newborns in 2 public hospitals	2003–2009	Overall study population (n = 12,295); Infants with cCMV (n = 121)	84% of neonates with cCMV underwent at least one ABR assessment (median age of 12 months) Seven of 10 infants with hearing loss were tested by OAE by 1 month of age, of whom 6 failed OAE and subsequent ABR
Marin et al.^38	Direct healthcare costs (antiviral use)	cCMV	Prospective analysis of the prevalence and clinical presentation of cCMV infection among a low-income population	2010–2012	Overall study population (n = 2100); Infants with cCMV (n = 25; 24 asymptomatic and 1 with symptoms)	For newborns with asymptomatic cCMV, 0% were treated with antiviral drugs until the second year of life
Global
Lachance et al.^39	Resource utilization (hospitalization, mechanical ventilation, renal replacement therapy)	CMV	Systematic literature review of association between CMV reactivation and survival, and resource utilization in immunocompetent critically ill patients	1990–2016	Immunocompetent critically ill patients with CMV admitted to ICU (n = 973) and/or receiving mechanical ventilation (n = 683).	The mean increase in length of ICU stays and mechanical ventilation for patients with CMV reactivation versus without CMV reactivation were 8.18 days and 6.6 days, respectively
Li et al.^40	Resource utilization (hospitalization)	CMV	Systematic literature review analyzed CMV infection and requirement for mechanical ventilation and duration of ICU stay in immunocompetent patients	1990–2016	Immunocompetent patients admitted to ICUs with/without CMV infection (n = 2398)	The mean increases in length of stay in ICU and duration of mechanical ventilation for patients with versus without CMV infection were 12 days (n = 875) and 9 days (n = 949), respectively

Abbreviations. ABR, auditory brainstem response; AU, anterior uveitis; CMV, cytomegalovirus; cCMV, congenital CMV; IBD, inflammatory bowel disease; ICU, intensive care unit; IV, intravenous; NICU, neonatal intensive care unit; OAE, otoacoustic emission; PSS, Posner-Schlossman syndrome; UC, ulcerative colitis; VLBW, very low birth weight.

Table 2. Summary of included economic evaluations of interventions related to CMV or cCMV (n = 7).

Reference	Type of analysis/outcomes	Disease/case type	Study design/methods	Study period	Study population and comparators	Top-line results
United States
Bergevin et al.^41	Cost-benefit	cCMV	Economic estimation of administrative and medical costs of cCMV screening and differential cost of treatment of cCMV positive infants	2014–2015	Infants who failed two newborn screening tests	The study suggests net benefits and societal savings from early identification and treatment of cCMV in infants under 3 weeks of age who failed newborn hearing screening (based on the cost of cochlear implants). The authors acknowledge that these estimates may be overly generous, as only a minority of eligible children would receive cochlear implants, this is likely offset by the exclusion of familial, societal, and educational benefits from this analysis
Albright et al.^16	Cost-effectiveness	cCMV and primary maternal CMV	Decision model comparing cost-effectiveness of universal versus risk-based screening using prenatal serum to detect cCMV	2018	Pregnant women	In estimating the costs and benefits of either universal prenatal serum screening or routine, risk-based screening of pregnant women for CMV infection (assumed CMV testing conducted prior to 20-week gestation or following observation of ultrasound abnormalities, respectively), the model predicted universal screening would be cost-effective in 62.8% of all modeled scenarios. The cost-effectiveness results for universal prenatal screening was significantly influenced by the incidence of primary CMV infection during pregnancy, with universal screening remaining cost-effective as long as the incidence of CMV was more than 0.89%
Gantt et al.^42	Cost-effectiveness	cCMV	Decision model comparing cost-effectiveness of universal and targeted newborn cCMV screening versus no cCMV screening	2014–2016	General newborn population	Estimated mean incremental costs of identifying 1 cCMV infection in newborns in the United States ranged from $2000 to $10,000 and $566 to $2832 for universal and targeted screening, respectively. Based on assumptions of antiviral treatment benefit in reducing hearing loss, including receipt of a cochlear implant, for symptomatic infants, modeling analyses estimated moderate direct costs of $10.86 (universal screening) and net savings of $0.90 (targeted screening) per newborn screened. Net savings of $21.34 (universal screening) and $10.66 (targeted screening) per newborn screened were estimated when costs related to loss-of-productivity were included
Dempsey et al.^43	Cost-effectiveness	cCMV and CMV	Decision model comparing costs, potential clinical impacts, and cost-effectiveness of the current strategy of no CMV vaccination versus a strategy where all adolescent females are vaccinated against CMV prior to their first pregnancy.	2010	Adolescent females	The incremental cost savings resulting from vaccination of adolescent females against CMV before their first pregnancies (three-dose schedule) was estimated at $32.3 million per 100,000 females and would substantially reduce the number of infants affected by long-term sequelae of CMV infection. Vaccination avoided 8 infant deaths, as well as reductions in the number of infants affected with hearing loss, vision loss, and mental retardation compared to no vaccination (14/100,000 versus 66/100,000, 1/100,000 versus 6/100,000, 5/100,000 versus 23/100,000, respectively. Universal vaccination of adolescent females to protect their future children against cCMV was cost-effective under a wide variety of conditions, assuming that vaccine efficacy against disease would need to be at least 61%
France
N’Diaye et al.^44	Cost-effectiveness	CMV	Decision model evaluating the cost-effectiveness of various strategies to vaccinate adolescent females, all women, or CMV seronegative women only versus no vaccination (current practice)	2014	Adolescent females	Systematic vaccination (three doses) of all eligible girls was found to be most cost-effective strategy for the prevention of cCMV infection in infants, followed by screening of all women and vaccinating only those who were seronegative for CMV infection
United Kingdom
Williams et al.^45	Cost-benefit	cCMV	Decision model cost analysis of targeted screening and treatment for cCMV-related hearing loss in otherwise asymptomatic infants	2010–2011	Infants with asymptomatic cCMV who were referred for further assessment after initial hearing screening tests	A cost analysis of targeted screening and subsequent treatment for cCMV-related SNHL in otherwise asymptomatic infants reported total costs of identifying, treating, and following up on identified cases were ₤6683 per case of SNHL and ₤113,615 per 100,000 infants undergoing newborn hearing screening
Australia
Beswick et al.^46	Cost-effectiveness	cCMV	Decision tree model evaluating cost-effectiveness of introducing targeted salivary cCMV testing into a newborn hearing screening program	2014–2016	Infants who did not pass their first and second newborn hearing screen (n = 283)	The differences in costs between implementing newborn hearing screening and not screening were negligible

Abbreviations. CMV, cytomegalovirus; cCMV, congenital CMV; SNHL, sensorineural hearing loss.

Table 3. Summary of other studies reporting the burden of cCMV (n = 1).

Reference	Type of analysis/outcomes	Disease/case type	Study design/methods	Study period	Study population and comparators	Top-line results
United Kingdom
Kadambari et al.^48	Hospital discharge records with viral diagnosis	cCMV	Population-based observational analysis of incidence of cCMV, HSV, VZV, and rubella with perinatal and maternal factors	1968–2016	Infants aged <1 month diagnosed with cCMV, HSV, VZV, and rubella from 1968 to 2016	The annual discharge rates of infants with cCMV infection increased from 4.6 patients per 100,000 during 1979–1985 to 22.3 patients per 100,000 in 2016

Abbreviations. cCMV, congenital cytomegalovirus; HSV, herpes simplex virus; VZV, varicella zoster virus.

Meyers J, Sinha A, Samant S, et al. The economic burden of congenital cytomegalovirus disease in the first year of life: a retrospective analysis of health insurance claims data in the United States. Clin Ther. 2019;41(6):1040 e1043–1056 e1043. doi: 10.1016/j.clinthera.2019.04.022.

 Web of Science ®Google Scholar

Inagaki K, Blackshear C, Palmer A, et al. Risk factors, geographic distribution, and healthcare burden of symptomatic congenital cytomegalovirus infection in the United States: analysis of a nationally representative database, 2000-2012. J Pediatr. 2018;199:118.e111–123.e111. doi: 10.1016/j.jpeds.2018.03.036.

 Web of Science ®Google Scholar

Grossberg LB, Ezaz G, Grunwald D, et al. A national survey of the prevalence and impact of cytomegalovirus infection among hospitalized patients with ulcerative colitis. J Clin Gastroenterol. 2018;52(3):241–245. doi: 10.1097/MCG.0000000000000736.

 PubMed Web of Science ®Google Scholar

Lucas A, Sinha A, Fowler KB, et al. A framework for assessing the lifetime economic burden of congenital cytomegalovirus in the United States. Cost Eff Resour Alloc. 2019;17:21. doi: 10.1186/s12962-019-0189-0.

 PubMed Web of Science ®Google Scholar

Lanzieri TM, Bialek SR, Bennett MV, et al. Cytomegalovirus infection among infants in California neonatal intensive care units, 2005–2010. J Perinat Med. 2014;42(3):393–399. doi: 10.1515/jpm-2013-0183.

 PubMed Web of Science ®Google Scholar

Tran C, Bennett MV, Gould JB, et al. Cytomegalovirus infection among infants in neonatal intensive care units, California, 2005 to 2016. Am J Perinatol. 2020;37(2):146–150. doi: 10.1055/s-0039-1683958.

 PubMed Web of Science ®Google Scholar

Korndewal MJ, Weltevrede M, van den Akker-van Marle ME, et al. Healthcare costs attributable to congenital cytomegalovirus infection. Arch Dis Child. 2018;103(5):452–457. doi: 10.1136/archdischild-2017-312805.

 PubMed Web of Science ®Google Scholar

Retzler J, Hex N, Bartlett C, et al. Economic cost of congenital CMV in the UK. Arch Dis Child. 2019;104(6):559–563. doi: 10.1136/archdischild-2018-316010.

 PubMed Web of Science ®Google Scholar

Ahmed I, Kassem W, Salam Y, et al. Outcome of cytomegalovirus colitis in inflammatory bowel disease with different regimes of ganciclovir. Middle East J Dig Dis. 2018;10(4):220–229. doi: 10.15171/mejdd.2018.114.

 PubMedGoogle Scholar

Walter E, Brennig C, Schöllbauer V, et al. How to save money: congenital CMV infection and the economy. In: Halwachs-Baumann G, editor. Congenital cytomegalovirus infection: epidemiology, diagnosis, therapy. Cham (Switzerland): Springer International Publishing; 2018. p. 121–144.

 Google Scholar

Delvincourt M, Lopez A, Pillet S, et al. The impact of cytomegalovirus reactivation and its treatment on the course of inflammatory bowel disease. Aliment Pharmacol Ther. 2014;39(7):712–720. doi: 10.1111/apt.12650.

 PubMed Web of Science ®Google Scholar

Touhami S, Qu L, Angi M, et al. Cytomegalovirus anterior uveitis: clinical characteristics and long-term outcomes in a French series. Am J Ophthalmol. 2018;194:134–142. doi: 10.1016/j.ajo.2018.07.021.

 PubMed Web of Science ®Google Scholar

Saletinger R, Poljak M, Strle F. Presence of human cytomegalovirus DNA in blood of patients with community-acquired pneumonia. Clin Microbiol Infect. 2015;21(1):97–102. doi: 10.1016/j.cmi.2014.09.001.

 PubMed Web of Science ®Google Scholar

Vergara A, Cilloniz C, Luque N, et al. Detection of human cytomegalovirus in bronchoalveolar lavage of intensive care unit patients. Eur Respir J. 2018;51(2):1701332. doi: 10.1183/13993003.01332-2017.

 PubMed Web of Science ®Google Scholar

Jedlińska-Pijanowska D, Czech-Kowalska J, Kłodzińska M, et al. Antiviral treatment in congenital HCMV infection: the six-year experience of a single neonatal center in Poland. Adv Clin Exp Med. 2020;29(10):1161–1167. doi: 10.17219/acem/125427.

 PubMed Web of Science ®Google Scholar

Maconi G, Lombardini M, Furfaro F, et al. Long-term outcome of inflammatory bowel diseases with cytomegalovirus colitis: effect of antiviral treatment. Eur J Gastroenterol Hepatol. 2014;26(10):1146–1151. doi: 10.1097/MEG.0000000000000175.

 PubMed Web of Science ®Google Scholar

Aoki H, Kitano T, Kitagawa D. Disease burden of congenital cytomegalovirus infection in Japan. J Infect Chemother. 2021;27(2):161–164. doi: 10.1016/j.jiac.2020.08.018.

 PubMed Web of Science ®Google Scholar

Maeda T, Babazono A, Nishi T, et al. The impact of opportunistic infections on clinical outcome and healthcare resource uses for adult T cell leukaemia. PLoS One. 2015;10(8):e0135042. doi: 10.1371/journal.pone.0135042.

 PubMed Web of Science ®Google Scholar

Lin C, Tomio J, Tanaka H, et al. Diagnosis and medical care for congenital cytomegalovirus infection: an observational study using claims data in Japan, 2010 to 2017. Medicine. 2020;99(10):e19419. doi: 10.1097/MD.0000000000019419.

 PubMed Web of Science ®Google Scholar

Niz Xavier PC, Gonçalves Vieira P, de Souza Arantes T, et al. Cytomegalovirus identification in blood and urine of newborns by nested polymerase chain reaction. West Indian Med J. 2015;65(2):291–294. doi: 10.7727/wimj.2014.378.

 PubMed Web of Science ®Google Scholar

Yamamoto AY, Mussi-Pinhata MM, Isaac Mde L, et al. Congenital cytomegalovirus infection as a cause of sensorineural hearing loss in a highly immune population. Pediatr Infect Dis J. 2011;30(12):1043–1046. doi: 10.1097/INF.0b013e31822d9640.

 PubMed Web of Science ®Google Scholar

Marin LJ, Santos de Carvalho Cardoso E, Bispo Sousa SM, et al. Prevalence and clinical aspects of CMV congenital infection in a low-income population. Virol J. 2016;13(1):148–148. doi: 10.1186/s12985-016-0604-5.

 PubMed Web of Science ®Google Scholar

Lachance P, Chen J, Featherstone R, et al. Association between cytomegalovirus reactivation and clinical outcomes in immunocompetent critically ill patients: a systematic review and Meta-Analysis. Open Forum Infect Dis. 2017;4(2):ofx029. doi: 10.1093/ofid/ofx029.

 PubMed Web of Science ®Google Scholar

Li X, Huang Y, Xu Z, et al. Cytomegalovirus infection and outcome in immunocompetent patients in the intensive care unit: a systematic review and meta-analysis. BMC Infect Dis. 2018;18(1):289. doi: 10.1186/s12879-018-3195-5.

 PubMed Web of Science ®Google Scholar

Bergevin A, Zick CD, McVicar SB, et al. Cost-benefit analysis of targeted hearing directed early testing for congenital cytomegalovirus infection. Int J Pediatr Otorhinolaryngol. 2015;79(12):2090–2093. doi: 10.1016/j.ijporl.2015.09.019.

 PubMed Web of Science ®Google Scholar

Albright CM, Werner EF, Hughes BL. Cytomegalovirus screening in pregnancy: a cost-effectiveness and threshold analysis. Am J Perinatol. 2019;36(7):678–687. doi: 10.1055/s-0038-1676495.

 PubMed Web of Science ®Google Scholar

Gantt S, Dionne F, Kozak FK, et al. Cost-effectiveness of universal and targeted newborn screening for congenital cytomegalovirus infection. JAMA Pediatr. 2016;170(12):1173–1180. doi: 10.1001/jamapediatrics.2016.2016.

 PubMed Web of Science ®Google Scholar

Dempsey AF, Pangborn HM, Prosser LA. Cost-effectiveness of routine vaccination of adolescent females against cytomegalovirus. Vaccine. 2012;30(27):4060–4066. doi: 10.1016/j.vaccine.2012.04.011.

 PubMed Web of Science ®Google Scholar

N’Diaye DS, Launay O, Picone O, et al. Cost-effectiveness of vaccination against cytomegalovirus (CMV) in adolescent girls to prevent infections in pregnant women living in France. Vaccine. 2018;36(10):1285–1296. doi: 10.1016/j.vaccine.2018.01.042.

 PubMed Web of Science ®Google Scholar

Williams EJ, Gray J, Luck S, et al. First estimates of the potential cost and cost saving of protecting childhood hearing from damage caused by congenital CMV infection. Arch Dis Child Fetal Neonatal Ed. 2015;100(6):F501–506. doi: 10.1136/archdischild-2014-306756.

 PubMed Web of Science ®Google Scholar

Beswick R, David M, Higashi H, et al. Integration of congenital cytomegalovirus screening within a newborn hearing screening programme. J Paediatr Child Health. 2019;55(11):1381–1388. doi: 10.1111/jpc.14428.

 PubMed Web of Science ®Google Scholar

Kadambari S, Pollard AJ, Goldacre MJ, et al. Congenital viral infections in England over five decades: a population-based observational study. Lancet Infect Dis. 2020;20(2):220–229. doi: 10.1016/S1473-3099(19)30416-5.

 PubMed Web of Science ®Google Scholar

Data availability statement 

The data summarized from this review are from published articles and are publicly available.