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Among 342 US infants with congenital cytomegalovirus treated with antivirals, 114 (33%) received ganciclovir (with or without valganciclovir) and 228 (67%) received valganciclovir only, for a median of 8 and 171 days, starting at a median of 15 and 45 days of life, respectively, with neutropenia diagnosed in 25% and 17%. [ABSTRACT FROM AUTHOR]

To critically review researchers' use of diagnosis codes to identify congenital cytomegalovirus (cCMV) infection or disease in healthcare administrative databases. Understanding the limitations of cCMV ascertainment in those databases can inform cCMV surveillance and health services research. We identified published studies that used diagnosis codes for cCMV or CMV in hospital discharge or health insurance claims and encounters records for infants to assess prevalence, use of services, or healthcare costs. We reviewed estimates of prevalence and of charges, costs, or expenditures associated with cCMV diagnosis codes. Five studies assessed hospitalizations with cCMV diagnosis codes recorded in hospital discharge databases, from the United States (n = 3), Australia (n = 1), and the United Kingdom (n = 1). Six other studies analyzed claims or encounters data from the United States (n = 5) or Japan (n = 1) to identify infants with cCMV codes. Prevalence estimates of recognized cCMV ranged from 0.6 to 3.8 per 10,000 infants. Economic analyses reported a wide range of per-hospitalization or per-infant cost estimates, which lacked standardization or comparability. The administrative prevalence of cCMV cases reported in published analyses of administrative data from North America, Western Europe, Japan, and Australia (0.6–3.8 per 10,000 infants) is an order of magnitude lower than the estimates of the true birth prevalence of 3–7 per 1,000 newborns based on universal newborn screening pilot studies conducted in the same regions. Nonetheless, in the absence of systematic surveillance for cCMV, administrative data might be useful for assessing trends in testing and clinical diagnosis. To the extent that cCMV cases recorded in administrative databases are not representative of the full spectrum of cCMV infection or disease, per-child cost estimates generated from those data may not be generalizable. On the other hand, claims data may be useful for estimating patterns of healthcare use and expenditures associated with combinations of diagnoses for cCMV and known complications of cCMV. [ABSTRACT FROM AUTHOR]

The article discusses a study by M. Diener and colleagues, published within the issue on the experience with targeted screening for congenital cytomegalovirus (cCMV) in Utah among infants who do not pass newborn hearing screening (NBHS). Topics include the benefits of targeted screening, the potential of universal screening of newborns for cCMV to increase detection of symptomatic infections, and controversial aspect of targeted screening in Utah.

Abstract: Background: Congenital cytomegalovirus (CMV) infection is a cause of sensorineural hearing loss (SNHL) in children, but the magnitude of its contribution is uncertain. Quantifying the impact of congenital CMV infection requires an evidence-based assessment using a standard case definition of hearing loss. Objectives: To determine the frequency of bilateral moderate to profound SNHL in children with congenital CMV infection and to estimate the CMV-attributable fraction of bilateral moderate to profound SNHL. Study design: A systematic review of studies of children with congenital CMV infection ascertained in an unbiased manner through universal newborn screening for CMV using viral culture in urine or saliva specimens in combination with a review of the literature on congenital CMV infection and hearing loss, including articles of all types. Results: Approximately, 14% of children with congenital CMV infection develop SNHL of some type, and 3–5% develop bilateral moderate to profound SNHL. Among all children with bilateral moderate to profound SNHL, we estimate that 15–20% of cases are attributable to congenital CMV infection. Conclusions: Congenital CMV infection is one of the most important causes of hearing loss in young children, second only to genetic mutations, and is potentially preventable. [Copyright &y& Elsevier]

OBJECTIVE: To examine the association between congenital cytomegalovirus (cCMV) and autism spectrum disorder (ASD) administrative diagnoses in US children. METHODS: Cohort study using 2014 to 2020 Medicaid claims data.We used diagnosis codes to identify cCMV (exposure), ASD (outcome), and covariates among children enrolled from birth through ≥4 to <7 years. Covariates include central nervous system (CNS) anomaly or injury diagnosis codes, including brain anomaly, microcephaly within 45 days of birth, cerebral palsy, epilepsy, or chorioretinitis. We used Cox proportional hazards regression models to estimate hazard ratios and 95% confidence intervals, overall and stratified by sex, birth weight and gestational age outcome (low birth weight or preterm birth), and presence of CNS anomaly or injury. RESULTS: Among 2 989 659 children, we identified 1044 (3.5 per 10 000) children with cCMV and 74 872 (25.0 per 1000) children with ASD. Of those with cCMV, 49% also had CNS anomaly or injury diagnosis codes. Children with cCMV were more likely to have ASD diagnoses (hazard ratio: 2.5; 95% confidence interval: 2.0-3.2, adjusting for birth year, sex, and region). This association differed by sex and absence of CNS anomaly or injury but not birth outcome. CONCLUSIONS: Children with (versus without) cCMV diagnoses in Medicaid claims data, most of whom likely had symptomatic cCMV, were more likely to have ASD diagnoses. Future research investigating ASD risk among cohorts identified through universal cCMV screening may help elucidate these observed associations. [ABSTRACT FROM AUTHOR]

The authors comment on antiviral treatment to preserve hearing in congenital cytomegalovirus (cCMV), the leading nongenetic cause of sensorineural hearing loss (SNHL) in children. Topics discussed include reason newborns are usually tested for cCMV, clinical trials about ganciclovir or valganciclovir conducted by the Collaborative Antiviral Study Group (CASG) and lack of evidence of the efficacy of antiviral medication on hearing preservation in infants with asymptomatic cCMV.

Cytomegalovirus (CMV) is the most common infectious cause of congenital malformation and a leading cause of developmental disabilities such as sensorineural hearing loss (SNHL), motor and cognitive deficits. The significant disease burden from congenital CMV infection (cCMV) led the US National Institute of Medicine to rank CMV vaccine development as the highest priority. An average of 6.7/1000 live births are affected by cCMV, but the prevalence varies across and within countries. In contrast to other congenital infections such as rubella and toxoplasmosis, the prevalence of cCMV increases with CMV seroprevalence rates in the population. The true global burden of cCMV disease is likely underestimated because most infected infants (85–90 %) have asymptomatic infection and are not identified. However, about 7–11 % of those with asymptomatic infection will develop SNHL throughout early childhood. Although no licensed CMV vaccine exists, several candidate vaccines are in development, including one currently in phase 3 trials. Licensure of one or more vaccine candidates is feasible within the next five years. Various models of CMV vaccine strategies employing different target populations have shown to provide substantial benefit in reducing cCMV. Although CMV can cause end-organ disease with significant morbidity and mortality in immunocompromised individuals, the focus of this vaccine value profile (VVP) is on preventing or reducing the cCMV disease burden. This CMV VVP provides a high-level, comprehensive assessment of the currently available data to inform the potential public health, economic, and societal value of CMV vaccines. The CMV VVP was developed by a working group of subject matter experts from academia, public health groups, policy organizations, and non-profit organizations. All contributors have extensive expertise on various elements of the CMV VVP and have described the state of knowledge and identified the current gaps. The VVP was developed using only existing and publicly available information. [ABSTRACT FROM AUTHOR]

Abstract: Background: Congenital cytomegalovirus (CMV) infection is a leading cause of sensorineural hearing loss (SNHL) and developmental disability in children. Early identification of infected children through screening could allow for early intervention and improvement in functional outcomes among the subset who develop sequelae. Objectives: To outline potential options and strategies for screening newborns for congenital CMV infection and to discuss barriers to screening and data needs to inform future policy decisions. Study design: Commentary based on the literature and expert opinion on newborn dried blood spot screening, newborn hearing screening/Early Hearing Detection and Intervention (EHDI) programs, and congenital CMV. Results: Although no population-based screening for congenital CMV is underway, pilot newborn screening studies using a variety of assays with urine or dried blood spot specimens are underway. Challenges to screening are both practical—uncertain sensitivity of blood spot assays suitable for large-scale screening and lack of infrastructure for collection of urine specimens; and evidentiary—the need to demonstrate improved outcomes and value of screening to offset the expense and potential adverse psychosocial consequences for children and families whose children require periodic monitoring but never develop sequelae. Conclusions: Screening for congenital CMV infection is a potentially important intervention that merits additional research, including the logistical feasibility of different screening options and psychosocial consequences for families. [Copyright &y& Elsevier]

Congenital cytomegalovirus (CMV) is a leading cause of non-genetic sensorineural hearing loss and neurodevelopmental disabilities among US children. Studies using administrative healthcare databases have identified infants with congenital CMV using diagnostic codes from the International Classification of Diseases, Ninth and Tenth Revision, Clinical Modification. Using Cerner Health Facts deidentified electronic health records, we assessed the sensitivity of CMV diagnostic codes among infants with laboratory confirmed congenital CMV infection (i.e. a positive CMV laboratory test – polymerase chain reaction, direct fluorescent antibody, or culture from urine, saliva, respiratory secretion or blood samples, or IgM serology – within 21 days of life). During 2010–2017, 668 congenital CMV cases were identified among 7,517,207 infants with encounters within 21 days of life, or 0.89 cases per 10,000 infants. The sensitivity of CMV diagnostic codes assigned within 21 and 90 days of life was 10.3% (95% CI: 8.2–12.9) and 11.1% (95% CI: 8.9–13.7), respectively. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To assess the prevalence, characteristics, and risk of sensorineural hearing loss (SNHL) in children with congenital cytomegalovirus infection identified through hospital-based newborn screening who were asymptomatic at birth compared with uninfected children. METHODS: We included 92 case-patients and 51 controls assessed by using auditory brainstem response and behavioral audiometry. We used Kaplan-Meier survival analysis to estimate the prevalence of SNHL, defined as ≥25 dB hearing level at any frequency and Cox proportional hazards regression analyses to compare SNHL risk between groups. RESULTS: At age 18 years, SNHL prevalence was 25% (95% confidence interval [CI]: 17%-36%) among case-patients and 8% (95% CI: 3%-22%) in controls (hazard ratio [HR]: 4.0; 95% CI: 1.2-14.5; P= .02). Among children without SNHL by age 5 years, the risk of delayed-onset SNHL was not significantly greater for case-patients than for controls (HR: 1.6; 95% CI: 0.4-6.1; P = .5). Among case-patients, the risk of delayed-onset SNHL was significantly greater among those with unilateral congenital/early-onset hearing loss than those without (HR: 6.9; 95% CI: 2.5-19.1; P < .01). The prevalence of severe to profound bilateral SNHL among case-patients was 2% (95% CI: 1%-9%). CONCLUSIONS: Delayed-onset and progression of SNHL among children with asymptomatic congenital cytomegalovirus infection continued to occur throughout adolescence. However, the risk of developing SNHL after age 5 years among case-patients was not different than in uninfected children. Overall, 2% of case-patients developed SNHL that was severe enough for them to be candidates for cochlear implantation. [ABSTRACT FROM AUTHOR]

Summary: Background: Congenital cytomegalovirus (CMV) infection is the leading infectious cause of congenital hearing loss and neurodevelopmental disability in developed countries. Information on congenital CMV infection in developing countries appears to be lacking. Methods: We conducted a systematic literature review to identify studies from developing countries with population-based samples of at least 300 infants that used laboratory methods established as reliable for the diagnosis of congenital CMV infection. Results: Most studies were excluded due to biased samples or inadequate diagnostic methods; consequently the search identified just 11 studies that were from Africa, Asia, and Latin America. The number of newborns tested ranged from 317 to 12 195. Maternal CMV seroprevalence ranged from 84% to 100%. CMV birth prevalence varied from 0.6% to 6.1%. CMV-associated impairments were not documented in most studies. Conclusions: Birth prevalence ranges were higher than for Europe and North America, as expected based on the higher maternal CMV seroprevalence. With very limited data available on sequelae, the disease burden of congenital CMV in developing countries remains largely unknown at this time. [Copyright &y& Elsevier]