Apparent diffusion coefficient values of the white matter in magnetic resonance imaging of the neonatal brain may help predict outcome in congenital cytomegalovirus infection.

BACKGROUND: White matter change is a well-known abnormality in congenital cytomegalovirus (cCMV) infection, but grading remains challenging and clinical relevance unclear. OBJECTIVE: To investigate if quantitative measurement of white matter apparent diffusion coefficient (ADC) values in magnetic resonance imaging (MRI) of the neonatal brain can predict outcome in cCMV. MATERIALS AND METHODS: A retrospective, single-center observational study, including patients with cCMV who had a neonatal brain MRI with diffusion-weighted imaging, was performed between 2007 and 2020. Regions of interest were systematically placed in the white matter on the ADC maps. Two pediatric radiologists independently scored additional brain abnormalities. Outcome measures were neonatal hearing and cognitive and motor development. Statistical analysis included simple and penalized elastic net regression. RESULTS: Neonatal brain MRI was evaluated in 255 patients (median age 21 days, 25-75 percentiles: 14-28 days, 121 male). Gyral abnormalities were noted in nine patients (3.5%), ventriculomegaly in 24 (9.4%), and subependymal cysts in 58 (22.7%). General white matter ADC was significantly higher in patients with neonatal hearing loss and cognitive and motor impairment (P< 0.05). For neonatal hearing loss, simple logistic regression using only general white matter was the best prediction model, with a receiver operating characteristic area under the curve (AUC)=0.76. For cognitive impairment, interacting elastic net regression, including other brain abnormalities and frontoparietal white matter ADC, performed best, with AUC=0.89. For motor impairment, interacting elastic net regression, including other brain abnormalities and deep anterior frontal white matter performed best, with AUC=0.73. CONCLUSION: Neonatal white matter ADC was significantly higher in patients with clinical impairments. Quantitative ADC measurement may be a useful tool for predicting clinical outcome in cCMV.

Risk Factors for Natural Hearing Evolution in Newborns With Congenital Cytomegalovirus Infection.

Importance: Congenital cytomegalovirus (cCMV) is the major cause of congenital nonhereditary sensorineural hearing loss in children. Currently, criteria to identify infants at increased risk for unfavorable hearing outcome are lacking. Objective: To identify risk factors associated with cCMV-related hearing improvement, hearing deterioration, and late-onset hearing loss. Design, Setting, and Participants: This multicenter cohort study included patients from 6 secondary and tertiary hospitals enrolled in the Flemish CMV registry (Belgium). Newborns with untreated cCMV infection with at least 4-year audiological follow-up were included. Patients who presented with other possible causes of sensorineural hearing loss were excluded. Data were collected for 15 years (January 1, 2007, to February 7, 2022) and analyzed from September 26, 2022, to January 16, 2023. Main Outcomes and Measures: Primary outcome was hearing evolution (per-ear analysis; described as stable hearing, improvement, or deterioration). The association of gestational characteristics, clinical findings, timing of seroconversion, viral load, and hearing status at birth with hearing evolution was investigated using effect sizes (Cramer V, odds ratio [OR], or Hedges g). Results: Of the 387 children, 205 of 385 with nonmissing data were male (53.2%), 113 (29.2%) had a symptomatic infection, and 274 (70.8%) had an asymptomatic infection. Every child was 4 years or older at final hearing evaluation. A total of 701 of 774 ears (90%) showed stable hearing (normal hearing or stable hearing loss since birth) over time. Late-onset hearing loss (normal hearing at birth followed by hearing loss) was present in 43 of 683 ears (6.3%). Among children with hearing loss present at birth, 24 of 34 ears (70.6%) had hearing deterioration, and 6 of 91 ears (6.6%) had hearing improvement. Prematurity was associated with a higher chance of hearing improvement (OR, 12.80; 95% CI, 2.03-80.68). Late-onset hearing loss was more prevalent in a first trimester infection (OR, 10.10; 95% CI, 2.90-34.48). None of the 104 ears of children with a third trimester seroconversion developed late-onset hearing loss. Conclusions and Relevance: Findings of this cohort study support that ongoing audiological follow-up for untreated children with congenital hearing loss is important, as the majority of patients had hearing deterioration. The timing of seroconversion was associated with the risk of developing late-onset hearing loss. These insights can aid in parental counseling, patient stratification, and follow-up. Future research should focus on the effect of treatment, the influence of determined risk factors, and the study of eventual new risk factors in patients at high risk to develop hearing loss.

Trends in neonatal morbidity and mortality for very low birthweight infants: a 20-year single-center experience.

OBJECTIVE: To describe trends in mortality and morbidity rates of very low birth weight infants as well as their pre-, peri- and postnatal characteristics over a period of 20 years' time. METHODS: Retrospective study in all very low birth weight infants admitted to the neonatal intensive care unit of the University Hospitals Ghent from 1 January 2000, to 31 December 2020. Mortality was the primary outcome variable with major morbidities being co-primary outcome variables. Pre-, peri- and postnatal characteristics are secondary outcome variables. We compared pre-, peri- and postnatal characteristics, as well as major morbidities between different groups with comparable rates of mortality. RESULTS: We included a total of 2037 very low birth weight infants and divided them in 3 epochs based on stepwise reductions in mortality in 2008 and 2013: 2000-2007 (n = 718), 2008-2012 (n = 506) and 2013-2020 (n = 813). Mortality decreased significantly over the years in all gestational ages, but predominantly in those with the youngest gestational age. Changes in obstetric and neonatal care were observed over time. Most significant changes were the increased use of antenatal corticosteroids, magnesium sulfate and surfactant. Intraventricular hemorrhage grade III/IV decreased significantly in all gestational ages. Significant increase in retinopathy of prematurity was observed. Bronchopulmonary dysplasia at 36 weeks and discharge home with oxygen is increasing in the total group. In those born below 26 weeks a slight increase in all major morbidities was observed especially of patent ductus arteriosus and retinopathy of prematurity. Increase of all other major morbidities seems to stabilize in epoch 3. The number of infants surviving without any major morbidity increases to almost 1/2 in all very low birth weight infants and to 1/10 in those born 24-25 weeks gestation. CONCLUSION: Analysis of the real-life experience showed that survival in very low birth weight infants significantly increased over time. Evolution of major morbidities will have to be carefully watched in the future.

Implications of isolated white matter abnormalities on neonatal MRI in congenital CMV infection: a prospective single-centre study.

OBJECTIVE: Investigating the clinical implications of isolated white matter abnormalities on neonatal brain MRI in congenital cytomegalovirus (CMV). DESIGN: Prospective, observational. PATIENTS/INTERVENTIONS: Two paediatric radiologists, blinded to clinical data, independently scored the white matter in 286 newborns with congenital CMV. After assessing interobserver variability, mean score was used to categorise white matter (normal, doubtful or abnormal). Patients with other brain abnormalities were excluded. MAIN OUTCOME MEASURES: Hearing and neuromotor evaluation. RESULTS: Cohen's weighted kappa was 0.79 (95% CI 0.73 to 0.84). White matter was normal in 121 patients, doubtful in 62, abnormal in 28. Median clinical follow-up was 12.0 months (IQR 12.0-27.7 months). Neonatal hearing loss occurred in 4/27 patients (14.8%) with abnormal, 1/118 patients (0.8%) with normal and 1/62 patients (1.6%) with doubtful white matter (p<0.01). Impaired cognitive development was seen in 3/27 patients (11.1%) with abnormal, 3/114 patients (2.6%) with normal and 1/59 patients (1.7%) with doubtful white matter (p=0.104). Alberta Infant Motor Scale (AIMS) was below P75 in 21/26 patients (80.8%) with abnormal, 73/114 patients (64.0%) with normal and 36/57 patients (63.2%) with doubtful white matter (p=0.231). In a subgroup of patients with minimal clinical follow-up of 18 months, AIMS score was below P75 in 10/13 patients (76.9%) with abnormal, 13/34 patients (38.2%) with normal and 7/20 patients (35.0%) with doubtful white matter (p<0.05). CONCLUSIONS: Abnormal white matter was associated with neonatal hearing loss and mild, lower motor scores. A tendency towards impaired cognitive development was seen. Patients with doubtful white matter did not show worse clinical outcome.

Association of antenatal magnesium sulfate with reduced late-onset sepsis in extreme preterm infants.

OBJECTIVES: Neonatal intensive care has changed extensively over the last decades resulting in improved survival of extreme preterm infants. However, improved survival is associated with prolonged hospitalization, mechanical ventilation and use of invasive devices, which are all predisposing factors for LOS. LOS is known to increase short- and long-term morbidities resulting in impaired neurodevelopmental outcome. Besides treatment with antibiotics and supportive care, there is an unmet need for adjunctive therapies to prevent neonatal sepsis and hereby improve outcome. METHODS: In a retrospective single-center design, we explored underlying pre-, peri- and postnatal factors in extreme preterm infants with and without LOS to potentially identify future strategies in the prevention of LOS in these infants. RESULTS: Associations formerly published could be confirmed, such as lower birth weight, longer duration of respiratory support, parenteral nutrition and NICU stay and a higher incidence of almost all neonatal morbidities. A new interesting finding was the fact that infants with LOS received more antenatal magnesium sulfate (p = 0.002). After nearest neighbor matching based on birth weight, gestational age, gender and multiplicity increased duration of parenteral nutrition and NICU stay, the incidence of PVL remained significantly different between the two groups (LOS/no LOS), but also the association between antenatal magnesium sulfate administration and less LOS held true (p = 0.004). CONCLUSION: In this study, extreme preterm infants receiving antenatal magnesium sulfate developed less LOS. Whether this is merely an associative factor reflecting illness severity or an interesting link for new preventive strategies for LOS, should be further explored.

Risk Factors for Hearing Loss at Birth in Newborns With Congenital Cytomegalovirus Infection.

Importance: With a prevalence between 0.2% and 6.1% of all live births, congenital cytomegalovirus (cCMV) infection is a major cause of congenital nonhereditary sensorineural hearing loss. Despite the large amount of research on cCMV-related hearing loss, it is still unclear which newborns are at risk of hearing loss. Objective: To identify independent risk factors for cCMV-related congenital hearing loss and predictors of hearing loss severity at birth. Design, Setting, and Participants: This cross-sectional study of newborns with cCMV infection used data included in the Flemish CMV registry that was collected from 6 secondary and tertiary hospitals in Flanders, Belgium, over 15 years (January 1, 2007, to February 7, 2022). Data were analyzed March 3 to October 19, 2022. Patients were included in the study after confirmed diagnosis of cCMV infection and known hearing status at birth. Patients who presented with other possible causes of sensorineural hearing loss were excluded. Main Outcomes and Measures: Primary outcome was hearing status at birth. Clinical, neurological, and laboratory findings along with the timing of seroconversion and blood viral load were separately considered as risk factors. Binary logistic regression was performed to identify independent risk factors for congenital hearing loss in newborns with cCMV. Effect sizes were measured using Hedges g, odds ratio, or Cramer V. Results: Of the 1033 newborns included in the study (553 of 1024 [54.0%] boys), 416 (40.3%) were diagnosed with symptomatic cCMV infection and 617 (59.7%) with asymptomatic cCMV infection. A total of 15.4% of the patients (n = 159) presented with congenital hearing loss; half of them (n = 80 [50.3%]) had isolated hearing loss. The regression model revealed 3 independent risk factors for congenital hearing loss: petechiae at birth (adjusted odds ratio [aOR], 6.7; 95% CI, 1.9-23.9), periventricular cysts on magnetic resonance imaging (MRI; aOR, 4.6; 95% CI, 1.5-14.1), and seroconversion in the first trimester (aOR, 3.1; 95% CI, 1.1-9.3). Lower viral loads were seen in patients with normal hearing compared with those with congenital hearing loss (median [IQR] viral load, 447.0 [39.3-2345.8] copies per milliliter of sample [copies/mL] vs 1349.5 [234.3-14 393.0] copies/mL; median difference, -397.0 [95% CI, -5058.0 to 174.0] copies/mL). Conclusions and Relevance: Findings of this cross-sectional study suggest that newborns with cCMV infection and petechiae at birth, periventricular cysts on MRI, or a seroconversion in the first trimester had a higher risk of congenital hearing loss. Clinicians may use these risk factors to counsel parents in the prenatal and postnatal periods about the risk of congenital hearing loss. Moreover, linking clinical features to hearing loss may provide new insights into the pathogenesis of cCMV-related hearing loss. The importance of viral load as a risk factor for congenital hearing loss remains unclear.

Predicting Early Vestibular and Motor Function in Congenital Cytomegalovirus Infection.

OBJECTIVES: Congenital cytomegalovirus (cCMV) can affect vestibular function, which is an important cornerstone for early motor development. This study aims to identify risk factors for early vestibular dysfunction with severe repercussions on the motor outcome. METHODS: This prospective cohort study included 169 cCMV-patients with complete vestibular assessment (lateral video Head Impulse Test and cervical Vestibular Evoked Myogenic Potentials) before the age of 18 months (mean 8.9, standard deviation 3.27 months). Motor results using the Alberta Infant Motor Scale were collected in 152 of these patients. Logistic and linear regression models were applied to identify risk factors for the vestibular and motor outcomes, respectively. RESULTS: The odds of developing early vestibular dysfunction were 6 times higher in patients presenting with hearing loss at birth compared to those born with normal hearing (p = .002). Within the latter group, significant predictors for vestibular dysfunction were (delayed-onset) hearing impairment at the time of vestibular testing (p = .003) and the presence of periventricular cysts on magnetic resonance imaging (p = .005). Remarkably, none of the patients infected during the third trimester of pregnancy (n = 14) developed early vestibular dysfunction. On average, vestibular-impaired patients had a z-score on the Alberta Infant Motor Scale that was 1.17 points lower than patients without vestibular deficit (p < .001). CONCLUSION: Early vestibular loss can have a significant adverse effect on motor development. Hearing and cranial imaging findings could facilitate the widespread implementation of a (targeted) vestibular assessment approach in the cCMV-population. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:1757-1765, 2023.

The Effect of (Val)ganciclovir on Hearing in Congenital Cytomegalovirus: A Systematic Review.

OBJECTIVE: To search for existing evidence of a beneficial effect of (val)ganciclovir on hearing in children with congenital cytomegalovirus (cCMV) infection and to identify future research questions. STUDY DESIGN: Systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, searches were performed in PUBMED, EMBASE, and WEB OF SCIENCE on December 15, 2021. METHODS: Studies providing ear-specific hearing results after treating children with cCMV-related hearing loss with (val)ganciclovir were retained. A meta-analysis [Peto odds ratio (OR), Review Manager 5.3] was performed to compare hearing outcome between treated and untreated children. The National Institutes of Health tool was used for quality assessment and heterogeneity was assessed with I2 statistics. RESULTS: Eighteen studies with a total of 682 treated patients were included for the systematic review. Our meta-analysis showed that treating symptomatic children with hearing loss resulted in more hearing improvement [Peto OR 7.72, 95% confidence interval (CI) 3.08-19.34] and less hearing deterioration (Peto OR 0.23, 95% CI 0.10-0.57). Relative to an improvement and deterioration rate of 9.4% and 28.2% in an untreated group, the rate of the treated group was 44.5% and 6.3%, respectively. CONCLUSIONS: There is sufficient evidence in literature to support treatment with (val)ganciclovir of children with symptomatic cCMV and hearing loss. However, still today, there is insufficient evidence of the potential beneficial role of (val)ganciclovir on hearing outcome of children with isolated hearing loss, late-onset hearing loss, and asymptomatic cCMV. The urgent need for future prospective, randomized clinical trials still exists. A standardization of definitions and treatment protocols would create uniformity in future studies. Laryngoscope, 132:2241-2250, 2022.

Cranial ultrasound and MRI: complementary or not in the diagnostic assessment of children with congenital CMV infection?

Whether or not cranial ultrasound (crUS) and cerebral magnetic resonance imaging (MRI) have both a place in the assessment of children with congenital cytomegalovirus infection (cCMV) remains a topic of discussion between research groups. Literature suggests that MRI is indicated only in children with abnormal crUS.In Flanders, Belgium, combined crUS and MRI was performed on 639 children with cCMV, referred for diagnostic assessment. Cranial US was classified as abnormal in the presence of striatal vasculopathy, calcifications, cysts, cystic germinolysis, and/or ventriculomegaly. MRI findings were classified as abnormal in the presence of gyration disorders, cerebellar abnormalities, ventriculomegaly, cysts, or pathologic white matter lesions.One in five children (93/480) with normal crUS showed abnormal findings on MRI. Of them, 85 (91.4%) were classified as symptomatic. In 37 of those 93 children (39.8%), classification as severely symptomatic was made based on MRI lesions alone. MRI and crUS proved to be complementary in the assessment of CNS involvement in children with cCMV. Long-term studies are needed to evaluate the importance of this finding with respect to outcome and benefit of therapy in this particular subgroup of patients with cCMV infection.Conclusion: Our findings support an enhanced role of MRI in the diagnosis of CNS involvement in children with cCMV infection. The ideal assessment should include both imaging techniques, as the strengths of each test compensate for the other's weaknesses. What is Known: • Congenital CMV infection involves the central nervous system with direct injury to and possible disruption of brain development. • Experts suggest that MRI is indicated only in children with abnormal crUS. What is New: • In almost 20% of our children with a normal cranial ultrasound, abnormalities were detected on MRI. • Our results suggest that performing both MRI and cranial US is important to obtain a complete assessment of central nervous system involvement in children with cCMV.

Brain MRI findings in newborns with congenital cytomegalovirus infection: results from a large cohort study.

OBJECTIVE: To investigate the spectrum and frequency of abnormalities on brain MRI in a large cohort of live newborns with congenital CMV (cCMV) infection. METHODS: Institutional review board approval and informed consent for neonatal MRI and data collection were obtained. Between January 2010 and January 2018, brain MRI was performed in 196 live newborns diagnosed with cCMV. Images were independently reviewed by 2 pediatric radiologists, blinded to clinical data. RESULTS: cCMV infection was clinically symptomatic in 26/191 newborns (13.6%). Brain MRI showed abnormalities in 76/196 patients (38.8%). MRI was abnormal in 20/26 clinically symptomatic patients (76.9%): 76.9% showed white matter lesions, 61.5% subependymal cysts, 46.2% ventriculomegaly, 26.9% ventricular adhesions, 26.9% gyral abnormalities, 24.0% calcifications, 15.4% cerebellar anomalies. MRI was abnormal in 55/165 (33.3%) clinically asymptomatic patients: 30.9% had white matter lesions, 15.8% subependymal cysts, 4.2% ventriculomegaly, 2.4% ventricular adhesions, 1.2% gyral abnormalities, 0.6% calcifications, none had cerebellar anomalies. Concomitant brain lesions were seen in all patients with gyral abnormalities, cerebellar anomalies, and calcifications and nearly all patients with subependymal cysts and ventriculomegaly. In all but 4 patients with other detected brain lesions, white matter abnormalities were simultaneously present. In 33/74 patients (45.2%), white matter lesions were seen as a sole abnormality. CONCLUSION: White matter lesions were the most common detected abnormality on brain MRI in newborns with congenital CMV. Since brain abnormalities were seen in more than 30% of clinically asymptomatic and 75% of clinically symptomatic newborns, MRI should be advised in all newborns diagnosed with cCMV. KEY POINTS: • Neonatal brain MRI showed abnormalities in more than 30% of clinically asymptomatic and 75% of symptomatic newborns with congenital cytomegalovirus infection. • White matter lesions were by far the most common detected abnormality, followed by subependymal cysts and ventricular dilatation. • Lesions in cCMV were often multiple, with many patients showing concomitant lesions.

Congenital CMV-Associated Hearing Loss: Can Brain Imaging Predict Hearing Outcome?

OBJECTIVES: Congenital cytomegalovirus (cCMV) infection is the leading cause of nonhereditary sensorineural hearing loss in childhood and is also associated with CNS abnormalities. The main objective is to investigate the prognostic value of neonatal cranial ultrasound (cUS) and cranial magnetic resonance imaging (cMRI) in predicting long-term hearing outcome in a large cohort of cCMV-infected symptomatic and asymptomatic patients. DESIGN: Data were prospectively collected from a multicentre Flemish registry of children with cCMV infection born between 2007 and 2016. Neonatal cUS and cMRI scans were examined for lesions related to cCMV infection. Audiometric results at different time points were analyzed. The imaging and audiometric results were linked and diagnostic values of cUS and cMRI were calculated for the different hearing outcomes. RESULTS: We were able to include 411 cCMV patients, of whom 40% was considered symptomatic at birth. Cranial ultrasound abnormalities associated with cCMV infection were found in 76 children (22.2% of the cUS scans), whereas cMRI revealed abnormalities in 74 patients (26.9% of the cMRI scans). A significant relation could be found between the presence of cUS or cMRI abnormalities and hearing loss at baseline and last follow-up. Cranial ultrasound and cMRI findings were not significantly correlated with the development of delayed-onset hearing loss. Specificity and sensitivity of an abnormal cUS to predict hearing loss at final follow-up were 84% and 43%, respectively compared with 78% and 39% for cMRI. Normal cUS and cMRI findings have a negative predictive value of 91% and 92%, respectively, for the development of delayed-onset hearing loss. CONCLUSIONS: Neuroimaging evidence of CNS involvement in the neonatal period is associated with the presence of hearing loss in children with a cCMV infection. Imaging abnormalities are not predictive for the development of delayed-onset hearing loss.

Congenital cytomegalovirus infection registry in flanders: opportunities and pitfalls.

In 2007, a prospective multicentre registry was set up to collect data on incidence and outcome of children with congenital cytomegalovirus infection in Flanders. A consensus was reached about management and follow up of cytomegalovirus-infected children. With this registration, we aimed at gathering information on congenital cytomegalovirus infection in Flanders and evaluating the consensus on management and therapy. Children with proven congenital cytomegalovirus infection were eligible for registration in the database. Information on prenatal and neonatal management, therapy and follow up until 6 years was obtained. Between 2007 and 2017, 686 children were registered. Data on the prenatal and neonatal characteristics in children with congenital cytomegalovirus infection are reported.Conclusion: In this article, we report on our experience of conducting a registry for cCMV in Flanders. Eleven years of collecting data on CMV in a multicenter setting have shown us some pitfalls and opportunities. We address some of the problems and aim at improving our data gathering. We encourage other groups to share their data. Better knowledge of the burden of the disease will be important to guide future management strategies.

Prospective multicenter comparison of urine culture with PCR on dried blood spots using 2 different extraction and PCR methods in neonates suspected for congenital cytomegalovirus infection.

To evaluate the potential of dried blood spots (DBS) as a congenital cytomegalovirus (cCMV) testing specimen, the laboratory diagnostic accuracy of polymerase chain reaction (PCR) on DBS was compared to viral urine cultures from neonates suspected for cCMV. Two different extraction methods (EasyMAG, bioMérieux versus Qiagen) and 2 real-time PCR protocols (in-house versus Argene) were compared. We were able to collect both DBS and urine samples in 6 Belgian neonatal units from 276 neonates suspected for cCMV registered in CMVREG (an online neonatal registry system). Forty-eight neonates (17.4%) were positive by viral culture in urine. Laboratory diagnostic accuracy parameters of DBS-PCR were both extraction method and PCR protocol dependent. Not all DBS-CMV-PCR methods successfully detected urine-culture-positive neonates born after first-trimester seroconversions. Interestingly, however, all urine-culture-positive neonates having clinical signs of cCMV did consistently score positive.

Hearing in Children with Congenital Cytomegalovirus Infection: Results of a Longitudinal Study.

OBJECTIVES: To evaluate hearing outcome, to characterize the nature of symptomatic and asymptomatic congenital cytomegalovirus (cCMV) infection and associated hearing loss, and to compare results with data from previous studies. STUDY DESIGN: A prospective multicenter registry was set up in 2007. Six centers participated in the development of a standardized protocol for diagnosis, treatment, and follow-up. Data were gathered in an online registry. Children (n = 379) with a documented cCMV infection and at least 2 separate audiologic evaluations were included. Audiometric results from a multicenter cohort study of children with cCMV infection with longitudinal observation were examined. RESULTS: Results from 123 children with a symptomatic and 256 children with an asymptomatic cCMV infection were analyzed. In the group with symptomatic cCMV, 63% had hearing loss, compared with 8% in the group with asymptomatic cCMV. Delayed-onset hearing loss occurred in 10.6% of symptomatic cCMV and in 7.8% of asymptomatic cCMV. In the group with symptomatic cCMV, 29.3% of children used some kind of hearing amplification; 1.6% in the group with asymptomatic cCMV used hearing amplification. CONCLUSIONS: Symptomatic and asymptomatic cCMV infections are a major cause of hearing loss in childhood. Reliable estimates of the long-term outcome of cCMV infection are mandatory to increase vigilance, especially among pregnant women and to draw attention to preventive measures, vaccine development, and prenatal and postnatal therapy. Universal screening of newborns for cCMV infection should be initiated and combined with longitudinal audiometric follow-up.

Hearing loss and congenital CMV infection: a systematic review.

BACKGROUND AND OBJECTIVE: Hearing loss caused by congenital cytomegalovirus (cCMV) infection was first observed in 1964. Today cCMV is the most common cause of nonhereditary sensorineural hearing loss in childhood. Our objective was to provide an overview of the prevalence of cCMV-related hearing loss, to better define the nature of cCMV-associated hearing loss, and to investigate the importance of cCMV infection in hearing-impaired children. METHODS: Two reviewers independently used Medline and manual searches of references from eligible studies and review articles to select cohort studies on children with cCMV infection with audiological follow-up and extracted data on population characteristics and hearing outcomes. RESULTS: Thirty-seven studies were included: 10 population-based natural history studies, 14 longitudinal cohort studies, and 13 retrospective studies. The prevalence of cCMV in developed countries is 0.58% (95% confidence interval, 0.41-0.79). Among these newborns 12.6% (95% confidence interval, 10.2-16.5) will experience hearing loss: 1 out of 3 symptomatic children and 1 out of 10 asymptomatic children. Among symptomatic children, the majority have bilateral loss; among asymptomatic children, unilateral loss predominates. In both groups the hearing loss is mainly severe to profound. Hearing loss can have a delayed onset, and it is unstable, with fluctuations and progression. Among hearing-impaired children, cCMV is the causative agent in 10% to 20%. Despite strict selection criteria, some heterogeneity was found between selected studies. CONCLUSIONS: This systematic review underscores the importance of cCMV as a cause of sensorineural hearing loss in childhood.

NEOREG: design and implementation of an online Neonatal Registration System to access, follow and analyse the data of newborns with congenital cytomegalovirus infection.

Today's registration of newborns with congenital cytomegalovirus (cCMV) infection is still performed on paper-based forms in Flanders, Belgium. This process has a large administrative impact. It is important that all screening tests are registered to have a complete idea of the impact of cCMV. Although these registrations are usable in computerised data analysis, these data are not available in a format to perform electronic processing. An online Neonatal Registry (NEOREG) System was designed and developed to access, follow and analyse the data of newborns remotely. It allows remote access and monitoring by the physician. The Java Enterprise layered application provides patients' diagnostic registration and treatment follow-up through a web interface and uses document forms in Portable Document Format (PDF), which incorporate all the elements from the existing forms. Forms are automatically processed to structured EHRs. Modules are included to perform statistical analysis. The design was driven by extendibility, security and usability requirements. The website load time, throughput and execution time of data analysis were evaluated in detail. The NEOREG system is able to replace the existing paper-based CMV records.

Detection of enteroviral RNA on Guthrie card dried blood of a neonate with fatal Coxsackie B3 myocarditis on day 17.

A fatal case of Coxsackie B3 myocarditis in a neonate is described. The clinical features became evident in the 3rd week of life, but enteroviral RNA was detected in the dried blood spot of the baby collected on day 4 after birth. This is the first report on the detection of enteroviral RNA in Guthrie card dried blood using reverse-transcriptase PCR. Materials and methods used are described in detail.