Vaccine value profile for cytomegalovirus.

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.

Retrospective Application of Sinusoidal Obstruction Syndrome/Veno-occlusive Disease Diagnostic Criteria in a Pediatric Hematopoietic Stem Cell Transplant Cohort.

Sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) posthematopoietic stem cell transplantation (HSCT) is often diagnosed using the modified Seattle (MS) or European Society for Blood and Marrow Transplantation (EBMT) criteria. We hypothesized that strict application of these criteria could affect the timing of diagnosis and incidence of SOS/VOD. We collected data on 215 transplants performed in 184 patients at a single pediatric hematopoietic stem cell transplantation center, which were divided into 3 cohorts. Clinical diagnosis and treatment of SOS/VOD was documented in 13% of transplants (cohort 1). On retrospective review, 49% of transplant events met either MS and/or EBMT criteria, however, were not diagnosed with SOS/VOD (cohort 2); remaining 38% of transplant events did not meet MS or EBMT criteria and were not diagnosed with SOS/VOD (cohort 3). Day+100 overall survival was significantly inferior for cohort 1 (78%) compared with cohorts 2 or 3 (92% and 95%, P=0.01) with no difference between cohorts 2 and 3 (P=0.5). Patients diagnosed with SOS/VOD >day+13 had worse day+100 overall survival when compared with those diagnosed ≤day13 (64.3% and 100%, respectively, P=0.02). This study highlights the value of careful clinical assessment to guide diagnosis and the need to refine diagnostic criteria for SOS/VOD in children.

Vestibular, Gaze, and Balance Disorders in Asymptomatic Congenital Cytomegalovirus Infection.

BACKGROUND AND OBJECTIVES: Congenital cytomegalovirus (cCMV) is the leading nongenetic cause of sensorineural hearing loss and developmental disabilities. Because there are limited data from studies of vestibular involvement in select groups of children with cCMV, the true frequency of vestibular disorders in cCMV is likely underestimated. Our objective for this study is to determine the prevalence of vestibular, gaze, and balance disorders in a cohort of children with asymptomatic cCMV. METHODS: Comprehensive vestibular, gaze, and balance assessments were performed in 40 children with asymptomatic cCMV. The function of semicircular canals of the inner ear and vestibulo-visual tract were assessed by measuring vestibulo-ocular reflex in a computer-driven motorized rotary chair; inner ear saccular function was assessed by using cervical vestibular evoked myogenic potential; gaze stability during head movement was assessed by using clinical dynamic visual acuity, and balance was assessed by using the sensory organization test and the Bruininks-Oseretsky Test of Motor Proficiency, Second Edition. Test results for each variable were compared with those of a control group without cCMV and/or compared to age-matched normative published data. RESULTS: Vestibular disorders were evident in 45% of the cohort on the basis of rotary chair and cervical vestibular evoked myogenic potential testing, suggesting abnormalities in semicircular canals, the utricle and saccule of the inner ear, and vestibulo-visual tracts. Additionally, 46% of the cohort had difficulties maintaining gaze during head movement, and one-third to one-half of the cohort had difficulties maintaining balance. CONCLUSIONS: Vestibular, gaze, and balance disorders are highly prevalent in children with asymptomatic cCMV. Systematic screening for vestibular disorders will be used to determine the full clinical impact for the development of effective interventions.

Comprehensive evaluation of risk factors for neonatal hearing loss in a large Brazilian cohort.

OBJECTIVES: To determine the incidence and risk factors of hearing loss (HL) in Brazilian neonates. STUDY DESIGN: 11,900 neonates were screened for hearing and congenital CMV (cCMV). Low and high-risk babies who did not pass their hearing screening and infants with cCMV were scheduled for a diagnostic audiologic evaluation. RESULTS: The incidence of HL was 2 per 1000 live-born infants (95% CI: 1-3). HL was higher in high-risk neonates than in low risk babies (18.6 vs. 0.3/1000 live births, respectively). Among infants exposed to isolated risk factors, association of HL with craniofacial abnormalities/syndromes (RR = 24.47; 95% CI: 5.9-100.9) and cCMV (RR = 9.54; 95% CI: 3.3-27.7) were observed. HL was 20 to 100-fold more likely in neonates exposed to ototoxic drugs in combination with cCMV or craniofacial/congenital anomalies. CONCLUSIONS: Strategies for the prevention of cCMV and exposure to ototoxic drugs may decrease the incidence of HL in this population.

SARS-CoV-2: Is it the newest spark in the TORCH?

Amid the rapidly evolving global coronavirus disease 2019 (COVID-19) pandemic that has already had profound effects on public health and medical infrastructure globally, many questions remain about its impact on child health. The unique needs of neonates and children, and their role in the spread of the virus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) should be included in preparedness and response plans. Fetuses and newborn infants may be uniquely vulnerable to the damaging consequences of congenitally- or perinatally-acquired SARS-CoV-2 infection, but data are limited about outcomes of COVID-19 disease during pregnancy. Therefore, information on illnesses associated with other highly pathogenic coronaviruses (i.e., severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome [MERS]), as well as comparisons to common congenital infections, such as cytomegalovirus (CMV), are warranted. Research regarding the potential routes of acquisition of SARS-CoV-2 infection in the prenatal and perinatal setting is of a high public health priority. Vaccines targeting women of reproductive age, and in particular pregnant patients, should be evaluated in clinical trials and should include the endpoints of neonatal infection and disease.

Evaluation of Commercial Molecular Diagnostic Methods for Detection and Determination of Macrolide Resistance in Mycoplasma pneumoniae.

We evaluated six commercial molecular tests targeting Mycoplasma pneumoniae, namely, the BioFire FilmArray respiratory panel (RP), the Meridian Alethia Mycoplasma Direct, the GenMark ePlex respiratory pathogen panel (RPP), the Luminex NxTAG RPP, the ELITech ELITe InGenius Mycoplasma MGB research use only (RUO) PCR, and the SpeeDx Resistance Plus MP assays. Laboratory-developed PCR assays at the University of Alabama at Birmingham and the Centers for Disease Control and Prevention were used as reference standards. Among 428 specimens, 212 were designated confirmed positives for M. pneumoniae The highest clinical sensitivities were found with the InGenius PCR (99.5%) and the FilmArray RP (98.1%). The Resistance Plus MP identified 93.3% of the confirmed-positive specimens, whereas 83.6, 64.6, and 55.7% were identified by the ePlex RPP, NxTAG RPP, and Mycoplasma Direct assays, respectively. There was no significant difference between the sensitivity of the reference methods and that of the FilmArray RP and InGenius assays, but the remaining four assays detected significantly fewer positive specimens (P < 0.05). Specificities of all assays were 99.5 to 100%. The Resistance Plus MP assay detected macrolide resistance in 27/33 specimens, resulting in a sensitivity of 81.8%. This study provides the first large-scale comparison of commercial molecular assays for detection of M. pneumoniae in the United States and identified clear differences among their performance. Additional studies are necessary to explore the impact of various test performances on patient outcome.

Contribution of Congenital Cytomegalovirus Infection to Permanent Hearing Loss in a Highly Seropositive Population: The Brazilian Cytomegalovirus Hearing and Maternal Secondary Infection Study.

BACKGROUND: The exact contribution of congenital cytomegalovirus infection (cCMVI) to permanent hearing loss (HL) in highly seropositive populations is unknown. We determined the contribution of cCMVI to HL and estimated the effectiveness of newborn hearing screening (HS) in identifying neonates with CMV-related HL. METHODS: A total of 11 900 neonates born from a population with ≥97% maternal seroprevalence were screened for cCMVI and HL. cCMVI was confirmed by detection of CMV-DNA in saliva and urine at age <3 weeks. RESULTS: Overall, 68 (0.6%; 95% confidence interval [CI], 0.4-0.7) neonates were identified with cCMVI. Of the 91 (0.8%) newborns who failed the HS, 24 (26.4%) were confirmed with HL, including 7 (29.2%; 95% CI, 17.2-59.3) with cCMVI. Another newborn with cCMVI passed the HS but was confirmed with HL at age 21 days. Of the 62 neonates with cCMVI who underwent a complete hearing evaluation, 8 (12.9%; 95% CI, 6.7-23.4) had HL and most (7/8; 87.5%; 95% CI, 46.6-99.7) were identified by HS. The rate of CMV-related HL was 8 per 11 887 neonates (0.7 per 1000 live births). The prevalence ratio of HL among neonates with cCMVI compared to CMV-uninfected neonates was 89.5 (95% CI, 39.7-202.0). No late-onset cCMVI-related HL was detected during a median follow-up of 36 months. CONCLUSIONS: cCMVI is an important cause of HL in childhood in all settings. Integrating targeted cCMVI screening among neonates who fail a HS could be a reasonable, cost-effective strategy to identify newborns with early-onset cCMVI-related HL.

A framework for assessing the lifetime economic burden of congenital cytomegalovirus in the United States.

BACKGROUND: In the United States (US), congenital cytomegalovirus infection (cCMVi) is a major cause of permanent disabilities and the most common etiology of non-genetic sensorineural hearing loss. Evaluations of prevention strategies will require estimates of the economic implications of cCMVi. We aimed to develop a conceptual framework to characterize the lifetime economic burden of cCMVi in the US and to use that framework to identify data gaps. METHODS: Direct health care, direct non-health care, indirect, and intangible costs associated with cCMVi were considered. An initial framework was constructed based on a targeted literature review, then validated and refined after consultation with experts. Published costs were identified and used to populate the framework. Data gaps were identified. RESULTS: The framework was constructed as a chance tree, categorizing clinical event occurrence to form patient profiles associated with distinct economic trajectories. The distribution and magnitude of costs varied by patient life stage, cCMVi diagnosis, severity of impairment, and developmental delays/disabilities. Published studies could not fully populate the framework. The literature best characterized direct health care costs associated with the birth period. Gaps existed for direct non-health care, indirect, and intangible costs, as well as health care costs associated with adult patients and those severely impaired. CONCLUSIONS: Data gaps exist concerning the lifetime economic burden of cCMVi in the US. The conceptual framework provides the basis for a research agenda to address these gaps. Understanding the full lifetime economic burden of cCMVi would inform clinicians, researchers, and policymakers, when assessing the value of cCMVi interventions.

Efficacy of inactivated trivalent influenza vaccine in rural India: a 3-year cluster-randomised controlled trial.

BACKGROUND: Paediatric vaccination against influenza can result in indirect protection, by reducing transmission to their unvaccinated contacts. We investigated whether influenza vaccination of children would protect them and their household members in a resource-limited setting. METHODS: We did a cluster-randomised, blinded, controlled study in three villages in India. Clusters were defined as households (ie, dwellings that shared a courtyard), and children aged 6 months to 10 years were eligible for vaccination as and when they became age-eligible throughout the study. Households were randomly assigned (1:1) by a computer-based system to intramuscular trivalent inactivated influenza vaccine (IIV3) or a control of inactivated poliovirus vaccine (IPV) in the beginning of the study; vaccination occurred once a year for 3 years. The primary efficacy outcome was laboratory-confirmed influenza in a vaccinated child with febrile acute respiratory illness, analysed in the modified intention-to-treat population (ie, children who received at least one dose of vaccine, were under surveillance, and had not an influenza infection within 15 days of last vaccine dose). The secondary outcome for indirect effectiveness (surveillance study) was febrile acute respiratory illness in an unvaccinated household member of a vaccine study participant. Data from each year (year 1: November, 2009, to October, 2010; year 2: October, 2010, to October, 2011; and year 3: October, 2011, to May, 2012) were analysed separately. Safety was analysed among all participants who were vaccinated with at least one dose of the vaccine. This trial is registered with ClinicalTrials.gov, number NCT00934245. FINDINGS: Between Nov 1, 2009, to May 1, 2012, we enrolled 3208 households, of which 1959 had vaccine-eligible children. 1010 households were assigned to IIV3 and 949 households were assigned to IPV. In 3 years, we vaccinated 4345 children (2132 with IIV3 and 2213 with IPV) from 1868 households (968 with IIV3 and 900 with IPV) with 10 813 unvaccinated household contacts. In year 1, influenza virus was detected in 151 (10%) of 1572 IIV3 recipients and 206 (13%) of 1633 of IPV recipients (total IIV3 vaccine efficacy 25·6% [95% CI 6·8-40·6]; p=0·010). In year 2, 105 (6%) of 1705 IIV3 recipients and 182 (10%) of 1814 IPV recipients had influenza (vaccine efficacy 41·0% [24·1-54·1]; p<0·0001). In year 3, 20 (1%) of 1670 IIV3 recipients and 81 (5%) of 1786 IPV recipients had influenza (vaccine efficacy 74·2% [57·8-84·3]; p<0·0001). In year 1, total vaccine efficacy against influenza A(H1N1)pdm09 was 14·5% (-20·4 to 39·3). In year 2, total vaccine efficacy against influenza A(H3N2) was 64·5% (48·5-75·5). Total vaccine efficacy against influenza B was 32·5% (11·3-48·6) in year 1, 4·9% (-38·9 to 34·9) in year 2, and 76·5% (59·4-86·4) in year 3. Indirect vaccine effectiveness was statistically significant only in year 3 (38·1% [7·4-58·6], p=0·0197) when influenza was detected in 39 (1%) of 4323 IIV3-allocated and 60 (1%) of 4121 IPV-allocated household unvaccinated individuals. In the IIV3 group, 225 (12%) of 1632 children in year 1, 375 (22%) of 1718 in year 2, and 209 (12%) of 1673 in year 3 had an adverse reaction (compared with 216 [13%] of 1730, 380 [21%] of 1825, and 235 [13%] of 1796, respectively, in the IPV group). The most common reactions in both groups were fever and tenderness at site. No vaccine-related deaths occurred in either group. INTERPRETATION: IIV3 provided variable direct and indirect protection against influenza infection. Indirect protection was significant during the year of highest direct protection and should be considered when quantifying the effect of vaccination programmes. FUNDING: US Centers for Disease Control and Prevention.

Seroconversion for Cytomegalovirus Infection During Pregnancy and Fetal Infection in a Highly Seropositive Population: "The BraCHS Study".

We determined the risk of seroconversion in seronegative pregnant women living in a high seroprevalence population. Cytomegalovirus (CMV)-immunoglobulin G reactivity was determined at the 1st trimester in all women and sequentially for seronegative women. A total of 1915 of 1952 (98.1%; 95% confidence interval [CI], 97.4%-98.7%) women were seropositive, and 36 (1.8%; 95% CI, 1.3%-2.6%) were seronegative. Five of the 36-seronegative women seroconverted for a cumulative rate of 13.9% (95% CI, 4.8%-30.6%). Congenital CMV infection was diagnosed in 1 of 36 infants (2.8%; 95% CI, 0.5%-63.9%) born to seronegative women compared with 8 of 1685 (0.5%; 95% CI, 0.2%-1.0%) infants born to seropositive mothers. Even with a high risk of primary infection in seronegative women, most CMV-infected infants were born to women with pre-existing seroimmunity.

Racial and Ethnic Differences in the Prevalence of Congenital Cytomegalovirus Infection.

OBJECTIVE: To evaluate the impact of race and ethnicity upon the prevalence and clinical spectrum of congenital cytomegalovirus infection (cCMV). STUDY DESIGN: From 2007 to 2012, 100 332 infants from 7 medical centers were screened for cCMV while in the hospital. Ethnicity and race were collected and cCMV prevalence rates were calculated. RESULTS: The overall prevalence of cCMV in the cohort was 4.5 per 1000 live births (95% CI, 4.1-4.9). Black infants had the highest cCMV prevalence (9.5 per 1000 live births; 95% CI, 8.3-11.0), followed by multiracial infants (7.8 per 1000 live births; 95% CI, 4.7-12.0). Significantly lower prevalence rates were observed in non-Hispanic white infants (2.7 per 1000 live births; 95% CI, 2.2-3.3), Hispanic white infants (3.0 per 1000 live births; 95% CI, 2.4-3.6), and Asian infants (1.0 per 1000 live births; 95% CI, 0.3-2.5). After adjusting for socioeconomic status and maternal age, black infants were significantly more likely to have cCMV compared with non-Hispanic white infants (adjusted prevalence OR, 1.9; 95% CI, 1.4-2.5). Hispanic white infants had a slightly lower risk of having cCMV compared with non-Hispanic white infants (adjusted prevalence OR, 0.7; 95% CI, 0.5-1.0). However, no significant differences in symptomatic cCMV (9.6%) and sensorineural hearing loss (7.8%) were observed between the race/ethnic groups. CONCLUSIONS: Significant racial and ethnic differences exist in the prevalence of cCMV, even after adjusting for socioeconomic status and maternal age. Although once infected, the newborn disease and rates of hearing loss in infants are similar with respect to race and ethnicity.

Congenital cytomegalovirus infection.

Each year, thousands of children are born with or develop permanent disabilities such as hearing loss, vision loss, motor and cognitive deficits from congenital CMV infection (cCMV). However, awareness of cCMV and its associated sequelae is very low in pregnant women and healthcare providers. Both targeted and universal approaches to screen newborns for CMV infection are now achievable due to recent scientific advances including the development of a rapid, high-throughput method for detecting CMV in saliva, the efficacy of antiviral treatment in symptomatic infants, and the demonstration of cost effectiveness of CMV screening. Future studies are needed to address gaps in our understanding on the role of non-primary maternal CMV infections, the evaluation of antiviral treatment in asymptomatic infants, and the implementation of prevention strategies for cCMV.

Cytomegalovirus Shedding in Seropositive Pregnant Women From a High-Seroprevalence Population: The Brazilian Cytomegalovirus Hearing and Maternal Secondary Infection Study.

Background: Most congenital cytomegalovirus (CMV) infections in highly seropositive populations occur in infants born to women with preexisting CMV seroimmunity. Although essential for developing prevention strategies, CMV shedding patterns in pregnant women with nonprimary infections have not been characterized. We investigated correlates of CMV shedding in a cohort of seropositive pregnant women. Methods: In a prospective study, saliva, urine, vaginal swabs, and blood were collected from 120 CMV-seropositive women in the first, second, and third trimesters and 1 month postpartum. Specimens were tested for CMV DNA by polymerase chain reaction. We analyzed the contribution of the specific maternal characteristics to viral shedding. Results: CMV shedding was detected at least once in 42 (35%) women. Mothers living with or providing daily care to young children (3-6 years) were twice as likely to shed CMV at least once compared to women with less exposure to young children (58% vs 26%; adjusted relative risk [aRR], 2.21; 95% confidence interval [CI], 1.37-3.56). Living in crowded households (≥2 people per room) was associated with viral shedding (64% vs 31%; aRR, 1.99; 95% CI, 1.26-3.13). Sexual activity as indicated by the number of sexual partners per year or condom use was not found to be a correlate of viral shedding. Conclusions: CMV shedding is relatively frequent in seropositive pregnant women. The association between virus shedding and caring for young children as well as crowded living conditions may provide opportunities for increased exposures that could lead to CMV reinfections in seropositive women.

Contribution of Breastfeeding to False-Positive Saliva Polymerase Chain Reaction for Newborn Congenital Cytomegalovirus Screening.

Real-time polymerase chain reaction (PCR) of saliva is highly sensitive for newborn congenital cytomegalovirus (CMV) screening. This study uses nationally published CMV seroprevalence and breastfeeding rates to estimate the contribution of CMV DNA in breast milk to false-positive saliva PCR results. The false-positive rates adjusted for breastfeeding ranged from 0.03% in white Hispanic persons to 0.14% in white non-Hispanic persons. Saliva CMV PCR for newborn screening is highly sensitive, and the low false-positive rates in this study suggest that saliva PCR results are unlikely to be significantly influenced by breastfeeding or other perinatal exposures.

Breast Milk Human Cytomegalovirus (CMV) Viral Load and the Establishment of Breast Milk CMV-pp65-Specific CD8 T Cells in Human CMV Infected Mothers.

The role of human cytomegalovirus (HCMV)-specific T-cell responses in breast milk of HCMV-seropositive mothers is not well defined. In these studies, we demonstrate that the frequency of cytomegalovirus (CMV)-pp65-specific T-cell responses in peripheral blood mononuclear cells (PBMCs) and breast milk cells (BMCs) is increased for CD8+ T cells in both sample sources when compared with CD4+ T cells. The frequency of pp55-specific CD8 T cells producing interferon γ (IFN-γ) alone or dual IFN-γ/granzyme rB producers is increased in breast milk compared with PBMCs. Lastly, we observed a positive correlation between breast milk viral load and the CD8 pp65-specific response, suggesting that local virus replication drives antigen-specific CD8 T cells into the breast.

Congenital cytomegalovirus infection in pregnancy and the neonate: consensus recommendations for prevention, diagnosis, and therapy.

Congenital cytomegalovirus is the most frequent, yet under-recognised, infectious cause of newborn malformation in developed countries. Despite its clinical and public health importance, questions remain regarding the best diagnostic methods for identifying maternal and neonatal infection, and regarding optimal prevention and therapeutic strategies for infected mothers and neonates. The absence of guidelines impairs global efforts to decrease the effect of congenital cytomegalovirus. Data in the literature suggest that congenital cytomegalovirus infection remains a research priority, but data are yet to be translated into clinical practice. An informal International Congenital Cytomegalovirus Recommendations Group was convened in 2015 to address these questions and to provide recommendations for prevention, diagnosis, and treatment. On the basis of consensus discussions and a review of the literature, we do not support universal screening of mothers and the routine use of cytomegalovirus immunoglobulin for prophylaxis or treatment of infected mothers. However, treatment guidelines for infected neonates were recommended. Consideration must be given to universal neonatal screening for cytomegalovirus to facilitate early detection and intervention for sensorineural hearing loss and developmental delay, where appropriate. The group agreed that education and prevention strategies for mothers were beneficial, and that recommendations will need continual updating as further data become available.

Newborn Dried Blood Spot Polymerase Chain Reaction to Identify Infants with Congenital Cytomegalovirus-Associated Sensorineural Hearing Loss.

OBJECTIVE: To determine the utility of dried blood spot (DBS) polymerase chain reaction (PCR) in identifying infants with cytomegalovirus (CMV) infection-associated sensorineural hearing loss (SNHL). STUDY DESIGN: Newborns at 7 US hospitals between March 2007 and March 2012 were screened for CMV by saliva rapid culture and/or PCR. Infected infants were monitored for SNHL during the first 4 years of life to determine sensitivity, specificity, and positive and negative likelihood ratios of DBS PCR for identifying CMV-associated SNHL. RESULTS: DBS at birth was positive in 11 of 26 children (42%) with SNHL at age 4 years and in 72 of 270 children (27%) with normal hearing (P = .11). The sensitivity (42.3%; 95% CI, 23.4%-63.1%) and specificity (73.3%; 95% CI, 67.6%-78.5%) was low for DBS PCR in identifying children with SNHL at age 4 years. The positive and negative likelihood ratios of DBS PCR positivity to detect CMV-associated SNHL at age 4 years were 1.6 (95% CI, 0.97-2.6) and 0.8 (95% CI, 0.6-1.1), respectively. There was no difference in DBS viral loads between children with SNHL and those without SNHL. CONCLUSIONS: DBS PCR for CMV has low sensitivity and specificity for identifying infants with CMV-associated hearing loss. These findings, together with previous reports, demonstrate that DBS PCR does not identify either the majority of CMV-infected newborns or those with CMV-associated SNHL early in life.