Congenital Cytomegalovirus DNA Research Articles

Is a Higher Amniotic Fluid Viral Load Associated with a Greater Risk of Fetal Injury in Congenital Cytomegalovirus Infection-A Systematic Review and Meta-Analysis.

Background: Numerous studies have aimed to predict prenatal and neonatal outcomes for pregnancies complicated by congenital cytomegalovirus (CMV). Presently, assessing CMV severity prenatally relies largely on fetal imaging. A controversy exists regarding CMV viral load (VL) and its association with fetal and neonatal sequelae. Objective: To perform a systematic review and meta-analysis investigating the association between CMV DNA VL in amniotic fluid and fetal and neonatal outcomes in pregnancies with congenital CMV. Results: All cohort, case-control and observational studies that compared outcomes of fetuses with congenital CMV and provided information on individual patient CMV VL quantified in copies per milliliter (c/mL) from inception to January 2023 were included, with no geographical or language restrictions. A total of 1251 citations were reviewed with eight studies meeting inclusion criteria and included in meta-analysis. Affected pregnancies had a higher VL in the amniotic fluid compared to those unaffected with a mean difference of 2.2e+7 (range 1.5e+7 to 2.8e+7). In subgroup analysis, the VL was significantly higher in the fetuses, with imaging findings related to CMV compared to asymptomatic fetuses with a mean difference of 4.1e+7 (95% CI 2.8e+7-5.4e+7). However, among babies with congenital CMV, the VL was not significantly different between symptomatic and asymptomatic babies. Conclusions: Amniotic fluid CMV VL is associated with fetal sequalae in congenital CMV, with a higher VL conferring a greater risk for prenatal injury.

Assessment of patients’ characteristics associated with the efficacy and safety of oral valganciclovir treatment for infants with symptomatic congenital cytomegalovirus disease

IntroductionInsurance coverage for oral valganciclovir (VGCV) began in Japan in April 2023 on the basis of results, including our clinical trials for symptomatic congenital cytomegalovirus (CMV) disease. The VGCV treatment is available throughout Japan, so clinicians must consider the likelihood of hearing improvement and the possibility of neutropenia before dosing. Materials and methodsWe performed a substudy of an investigator-initiated, single-arm, prospective, multicenter, clinical trial in which 24 infants with symptomatic congenital CMV disease were orally administered 16 mg/kg VGCV twice daily for 6 months as an intervention. We examined the infants’ baseline characteristics associated with improved hearing impairment or a severely reduced neutrophil count. ResultsOf the 24 patients, 4 had normal hearing on assessment of their ear with the best hearing. Hearing impairment improved in 14 patients and did not respond to VGCV treatment in 6 patients at the 6-month hearing assessment. CMV DNA levels in plasma at baseline were higher in patients in whom hearing did not respond to treatment. A neutrophil count <500/mm3 occurred in 5 (21%) patients for the first 6 weeks and in 8 (33%) patients for the first 6 months. A neutrophil count at screening and the lowest neutrophil count over the 6 months showed the highest correlation (r = 0.477, p = 0.019). ConclusionsInfants with a low plasma viral load at screening tend to have an improvement in hearing impairment. Clinicians should be aware of neutropenia during VGCV treatment particularly in patients with a low neutrophil count during screening.

Oral Valganciclovir Therapy in Infants Aged ≤2 Months with Congenital Cytomegalovirus Disease: A Multicenter, Single-Arm, Open-Label Clinical Trial in Japan.

Our aims were to determine the clinical impact of oral valganciclovir (VGCV) in infants aged ≤2 months with congenital cytomegalovirus (CMV) disease and evaluate the efficacy of VGCV when initiated beyond the neonatal period. The multicenter, single-arm, open-label clinical trial was conducted in Japan. Twenty-five infants aged ≤2 months with congenital CMV disease involving the central nervous system were enrolled and treated with VGCV for 6 months. The primary endpoint was the change in the whole blood CMV load before and after treatment. The secondary endpoint was the change in the auditory brainstem response (ABR) before and after treatment. Changes in ABR were assessed between the younger and older age groups (≤ and >30 days at treatment initiation). Of the 25 patients, one was excluded owing to epilepsy before VGCV administration. The median change in the CMV DNA level in whole blood was −246.0 IU/mL. The best ear and total ear assessments based on ABR were categorized as (improved + unchanged) after treatment for 100% and 93.8%, respectively. No differences in hearing efficacy were observed between the younger and older age groups. Oral VGCV is a potential therapeutic option for treating infants aged ≤2 months with congenital CMV disease.

Urine qRT-PCR assay as a screening tool for the detection of congenital human cytomegalovirus infection of infants

Congenital cytomegalovirus (CMV) infection is the most common infectious cause of birth defects. It may cause both, immediate and long term health problems in infants. These include variety of symptoms, such as hearing loss, microcephaly, jaundice, hepatosplenomegaly and seizures. In more severe cases CMV infection can cause the death of an unborn baby and loss of pregnancy. Despite being one of the most extensively studied vertically transmitted infections recently, the adverse effects of vertically transmitted CMV infection are still not well presented to the general public, resulting in a low awareness among potential expectant mothers in Bosnia and Herzegovina. This study aims to elucidate the sensitivity of urine samples for CMV detection in infants as well as to reflect the importance of quantitative real-time PCR (qRT-PCR) in diagnostics of CMV infection in infants. qRT-PCR was used in this study as a technique for the screening of CMV DNA in a cohort of patients based in Sarajevo Canton. These results have shown that urine samples are sufficiently sensitive for the detection of CMV DNA in infants. Furthermore, the simultaneous analysis of several patients has shown a higher number of CMV DNA copies amplified in urine compared to blood samples, derived from the same patient, thus proposing urine as a reliable sample of choice for congenital CMV diagnostics. These findings may propose a need to classify qRT-PCR CMV test among one of the recommended first-trimester pregnancy screening tests, which could help in early detection of CMV infection in Sarajevo Canton.

Targeted and universal screen in term and preterm infants for congenital CMV infection

Background: The aims of this study were to evaluate the incidence of congenital cytomegalovirus (CMV) in term and near-term infants who fail hearing screen (target screening), the incidence of congenital CMV infections in infants born before 33 weeks of gestation (universal screening) and the incidence of infants who need pharmacologic treatment for congenital CMV associated sensorineural hearing loss (SNHL).Methods: This was a retrospective cohort study that assessed two groups of infants born between 2014 and 2017. The first group consisted of infants born between 33 and 42 weeks gestation and the second group, of infants born before 33 weeks gestation. Targeted CMV screening was performed in the first group who either failed neonatal hearing screen or were growth retarded. Universal screen was performed in the second group of infants. CMV DNA was tested in urine samples using real time PCR soon after birth.Results: In the first group, 2078 infants were assessed, 19 (0.9%) were found to be CMV positive and in 9 (42%) valganciclovir treatment was initiated. In the second group, out of 549 urine samples/infants, none was positive for CMV DNA soon after birth.Conclusions: A joint strategy of targeted CMV screening in infants who fail hearing screen test with universal screen of premature infants can select infants at risk of hearing impairment due to congenital CMV soon after birth, allows for timely initiation of treatment and prevents dilemmas regarding congenital CMV diagnosis in infants who fail hearing screen in a later age until universal screen will be widely adopted.

Development of highly efficient protocols for extraction and amplification of cytomegalovirus DNA from dried blood spots for detection and genotyping of polymorphic immunomodulatory genes.

Congenital cytomegalovirus (CMV) infection is a major cause of birth defects ranging from developmental disorders to stillbirth. Most newborns affected by CMV do not present with symptoms at birth but are at risk of sequelae at later stages of their childhood. Stored dried blood spots (DBS) taken at birth can be used for retrospective diagnosis of hereditary diseases, but detection of pathogens is challenged by potentially low pathogen concentrations in the small blood volume available in a DBS. Here we test four different extraction methods for optimal recovery of CMV DNA from DBS at low to high CMV titers. The recovery efficiencies varied widely between the different extractions (from 3% to 100%) with the most efficient method extracting up to 113-fold more CMV DNA than the least efficient and 8-fold more than the reference protocol. Furthermore, we amplified four immunomodulatory CMV genes from the extracted DNA: the UL40 and UL111A genes which occur as functional knockouts in some circulating CMV strains, and the highly variable UL146 and US28 genes. The PCRs specifically amplified the CMV genes at all tested titers with sufficient quality for sequencing and genotyping. In summary, we here report an extraction method for optimal recovery of CMV DNA from DBSs that can be used for both detection of CMV and for genotyping of polymorphic CMV genes in congenital CMV infection.

Potential Biomarkers for Predicting Congenital Cytomegalovirus Infection

Early diagnosis and treatment of infants with symptomatic congenital cytomegalovirus (CMV) infection may improve neurological outcomes. For this reason, prenatal detection of newborns at high risk for congenital CMV infection is important. A polymerase chain reaction (PCR) assay for CMV DNA in the amniotic fluid is the gold standard for the diagnosis of intrauterine CMV infection; however, amniocentesis is an invasive procedure. Recently, we have found that the presence of CMV DNA in the maternal uterine cervical secretion is predictive of the occurrence of congenital CMV infection in CMV immunoglobulin M (IgM)-positive pregnant women. In contrast, we have suggested that maternal serological screening for primary CMV infection using CMV-specific immunoglobulin G (IgG), the IgG avidity index, or CMV-specific IgM overlooks a number of newborns with congenital CMV infection. We will review current knowledge of the potential biomarkers for predicting congenital CMV infection.

Ultrasound screening and clinical manifestations of congenital cytomegalovirus infection in fetuses

Objective To investigate the value of ultrasound screening for congenital cytomegalovirus (CMV) infection in fetuses and to summarize the clinical manifestations. Methods From January 2012 to December 2017, we retrospectively analyzed the clinical data of 905 gravidas who received invasive prenatal diagnosis in Fujian Provincial Maternity and Children's Hospital for abnormal prenatal ultrasound findings including ventriculomegaly, intracranial calcification, microcephaly, echogenic bowel and fetal growth restriction (FGR). CMV DNA loads in amniotic fluid and neonatal urine were detected by real-time polymerase chain reaction. CMV-specific IgM and IgG in umbilical cord and neonatal peripheral blood were detected by commercial enzyme 1inked immunosorbent assay kits. Eighteen fetuses with normal karyotype were diagnosed as congenital CMV infection. Relationships of ultrasound features and CMV DNA loads in amniotic fluid to pregnancy outcomes were analyzed with χ2 test or Fisher's exact test. Results (1) Congenital CMV infection was detected in 18 fetuses in this study with an detection rate of 1.99% (18/905). Three pregnancies were terminated immediately after the diagnosis was confirmed, two terminated when the ventriculomegaly progressed, five terminated for hydrocephaly and eight continued to delivery. (2) Congenital CMV infection rate was significantly higher in those with two or more ultrasound abnormalities than that in those with only one abnormal indicator [3.92%(8/204) vs 1.28%(9/701), χ2=4.619, P=0.032]. Fetuses with craniocerebral abnormalities were more likely to have congenital CMV infection than those without [3.11%(13/418) vs 0.82%(4/487), χ2=6.392, P=0.012]. (3) Among the 18 fetuses with congenital CMV infection, those with serious ultrasound abnormalities had a significantly higher rate of adverse outcomes than those without (11/11 vs 3/7, Fisher's exact test, bilateral P=0.043). No significant difference in the rate of adverse outcomes was found between fetuses with low and high CMV DNA loads in amniotic fluid (3/4 vs 12/14, Fisher's exact test, bilateral P=1.000). Conclusions Ultrasound abnormalities including ventriculomegaly, intracranial calcification, microcephaly, echogenic bowel and FGR, especially those with multiple abnormalities and brain abnormalities, increased risk of congenital CMV infection. Congenital CMV fetuses with serious ultrasound abnormalities has adverse outcomes. Key words: Cytomegalovirus infections; Fetal diseases; Ultrasonography, prenatal; Pregnancy outcome

Evaluation of cytomegalovirus DNA in periymphatic fluid in patients with sensorineural hearing loss using PCR technique

Purpose:Congenital cytomegalovirus (CMV) infection is the most common congenital infection in developing countries with sensorineural hearing loss (SNHL) being the most important of its long-term sequelae. The aim of this research was to evaluate the amount of CMV DNA in perilymph of patients with SNHL undergoing cochlear implant (CI) procedure by Polymerase chain reaction (PCR) technique.Materials and Methods:This cross-sectional and prospective study was conducted in a group of patients with ages ranging from 1 to 7 years. The perilymph was extracted preoperatively using a Yale spinal needle after opening of the round window. 25 microliters of perilymph was extracted and stored at -80 degrees centigrade. PCR technique was employed to detect CMV DNA. The data was collected and statistically analyzed.Results:A sample size of 41 patients with bilateral profound SNHL was selected. After cochlear implantation, CMV DNA evaluation was performed which was found positive in 18 patients (43.9%) and negative in 23 patients (56.09%) with a statistically significant relationship. No statistical relationship was found with gender, age and other comorbid disorders. 3-6 months’ follow-up was individually performed to compare Categories of Auditory Performance (CAP) and Speech Intelligibility Rating (SIR) tests in CMV DNA positive and negative patients, yielding different results which were statistically insignificant.Conclusion:The early detection of CMV infection with real time PCR technique enables us to perform viral screening tests in patients with SNHL.

Recovery of cytomegalovirus DNA from newborn saliva samples by different methods

BackgroundPolymerase chain reaction (PCR) testing of saliva swabs has been shown to be an attractive method to screen for congenital cytomegalovirus (CMV) infection. However, few data are available regarding the impact of pre-analytic methods on CMV DNA recovery from saliva samples under various conditions. ObjectivesThe purpose of this study was to evaluate the impact of various transport media and transport conditions on the recovery of CMV DNA from spiked and clinical saliva samples from newborns using PCR testing. Study designNegative control saliva samples were spiked with known concentrations of World Health Organization CMV standards. Collection was simulated using filter paper and different types of swabs which were stored either dry or in various transport media at specified temperatures. Specimens were tested by quantitative PCR at multiple time points. Results were compared with samples taken from newborns infected with CMV using the same methods. ResultsNucleic acid stabilization media demonstrated superior CMV stability for up to 3 weeks. Also observed was a reduction in the quantity of spiked CMV DNA over time in swab samples stored at room temperature without media or in conventional universal transport media. Swab samples from newborns infected with CMV did not demonstrate loss of CMV DNA after a week of room temperature storage in nucleic acid stabilization media or conventional universal transport media. ConclusionsAlthough nucleic acid preservation media appear to enhance CMV DNA recovery from spiked control samples over prolonged transport times and diverse conditions, this differential yield appears be to less significant for actual clinical samples collected from infected newborns. Further evaluation of pre-analytic conditions using actual clinical samples is warranted.

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

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. 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. 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. 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.

Incidence of UL97 Resistance Mutations in Infants with Congenital Cytomegalovirus Disease Receiving 6 Months of Oral Valganciclovir Therapy

BackgroundA recently completed Phase 3 randomized, controlled, double-blind, multicenter study of infants with symptomatic congenital cytomegalovirus (CMV) disease receiving 6 months of oral valganciclovir (VGCV) therapy represents the largest such population in which to evaluate treatment-emergent antiviral resistance. The most common mechanism of CMV antiviral resistance occurs through mutations in the CMV UL97 gene that confer resistance to ganciclovir (GCV). Genotypic resistance analyses were performed on infants receiving 6 months of VGCV to assess the incidence of antiviral resistance due to UL97 sequence variants.MethodsResistance analyses were performed by conventional DNA sequencing of the UL97 gene at multiple time points. Following CMV DNA extraction from frozen whole blood specimens, the UL97 gene was amplified with a double nested polymerase chain reaction method and sequenced to identify polymorphisms and mutations that might confer GCV resistance.ResultsForty-six infants with symptomatic CMV disease who received a 6-month course of VGCV underwent resistance analysis to identify UL97 sequence variants. In addition to a range of natural polymorphisms known to have no effect on antiviral susceptibility, 2 subjects developed UL97 mutations known to confer resistance to GCV (A594V and G598S detected in one subject; E596G detected in another), yielding an incidence of 4%. Each of these resistance mutations occurred in specimens collected after at least 4 months of antiviral therapy. As evaluated in the original Phase 3 trial, neither of these infants showed an improvement in hearing outcome.ConclusionThe development of treatment-emergent UL97 resistance mutations was determined in a controlled study population of infants with congenital CMV disease receiving 6 months of VGCV. This targeted resistance analysis demonstrated an incidence approaching the total incidence of antiviral resistance for CMV disease in some immunocompromised populations, such as solid-organ transplant recipients. Further studies within this study population are warranted to elucidate the risk of emerging antiviral resistance and to assess clinical impact as well as the potential need for combination antiviral therapy.Disclosures All authors: No reported disclosures.

Association between cerebrospinal fluid viral load and hearing loss in neonates with congenital symptomatic cytomegalovirus infection

Objective To determine the relationship between the viral load of cerebrospinal fluid (CSF) and sensorineural hearing loss (SNHL) in newborns with symptomatic congenital cytomegalovirus (CMV) infection. Methods The study cohort comprised 36 newborns with symptomatic congenital CMV infection. CSF from all of the patients were analyzed for the presence of CMV DNA by PCR. Audiological function were performed on them by brain stem auditory evoked potential at birth, at 6 and 12 months of age. Results (1) Of the 36 newborns, 15 cases (41.7%) had positive CSF PCR result, 17 cases (47.2%) had SNHL.(2) The prevalence of SNHL in the group of newborns with positive CSF PCR result was 60.0%(9/15), and it was 38.1%(8/21) in the group of newborns with negative CSF PCR result, there was no significant difference of the prevalence of SNHL between the two groups (P=0.194). (3) In newborns with positive CSF PCR result, the amounts of CSF CMV DNA was not different between the newborns with SNHL and normal hearing (3.35±0.68 vs. 3.17±0.56, P=0.36). Conclusion A positive CSF PCR result and the CMV viral load of CSF did not correlate with SNHL. Key words: Cytomegalovirus; Viral load; Cerebrospinal fluid; Sensorineural hearing loss; Neonate

Retrospective diagnosis of congenital cytomegalovirus infection in children with autism spectrum disorder but no other major neurologic deficit.

Congenital cytomegalovirus (CMV) infection can cause a variety of neurological deficits of delayed onset in infants who are asymptomatic at birth. The aim of this study was to investigate the prevalence of congenital CMV infection among children with autism spectrum disorder (ASD) in Nagasaki, Japan. Twenty-nine children with ASD who were born in Nagasaki and had no other major neurological deficits were recruited. Two of the patients were excluded due to significant perinatal events. The remaining 27 children were investigated retrospectively for congenital CMV infection by analyzing dried blood spot samples or dried umbilical cords for CMV DNA using real-time PCR. CMV DNA was detected in two (7.4%) of the 27 children. Neither of the patients had perinatal histories suggestive of congenital CMV disease or other neurological deficits, including hearing impairment and epilepsy. The severity of their autistic disorders varied considerably. The rate of congenital CMV infection in this study (two of 27 children with ASD), which was significantly (p=0.004) higher than the incidence of congenital CMV infection in Nagasaki (0.31%, 10/3230 live births), suggests the involvement of congenital CMV infection in a portion of children with ASD, although definite diagnosis was not obtained due to limited clinical data of the study subjects.

Saliva sample for screening of congenital cytomegalovirus

Objective To investigate the feasibility of congenital cytomegalovirus (CMV)infection screening by saliva polymerase chain reaction.Methods From November 1,2010 to February 29,2012,6733 newborns born in Changzhou Maternal and Child Health Care Hospital were enrolled.Saliva samples (0.2 ml) were collected within 3 days after birth,CMV-DNA was detected by real time-polymerase chain reaction and hearing screening was done with EroScan transient-evoked otoacoustic emissions at the same time.The positive rate of congenital CMV infection screening was calculated and clinical manifestations were analyzed.Chi square test was applied to statistical analysis.Results Totally 6733 newborns were screened and 107 of them were found to be positive with CMV DNA,the positive rate was 1.59％ (107/6733),among which 88 were asymptomatic (82.2％) and 19 were symptomatic (17.8 ％).The major clinical manifestations of the neonates with positive CMVDNA were pathological jaundice (13 cases),hepatomegaly (5 cases),granulocytopenia,thrombocytopenic purpura,anemia and small for gestational age (two cases each).Fourteen newborns had only one major clinical manifestation,three newborns had two major clinical manifestations and two newborns had three major clinical manifestations.There was no statistical difference between newborns with positive and negative CMV DNA on hearing screening [hearing loss in one ear:8.4％ (9/107) vs 5.8％ (382/6626); hearing loss in two ears:3.7 ％ (4/107) vs 2.4 ％ (159/6626),x2 =2.776,P=0.241].Conclusion It is feasible to screen congenital CMV infection with saliva sample. Key words: Cytomegalovirus infections ; Saliva ; Specimen handling ; Screening

Clinical, Biochemical, and Neuroimaging Findings Predict Long-Term Neurodevelopmental Outcome in Symptomatic Congenital Cytomegalovirus Infection

To evaluate clinical, biochemical, and neuroimaging findings as predictors of neurodevelopmental outcome in patients with symptomatic congenital cytomegalovirus (CMV). The study cohort comprised 26 patients with symptomatic congenital CMV born between 1993 and 2009 in a single center. Absolute and weight deficit-adjusted head circumference were considered. Cerebrospinal fluid (CSF) investigations included standard cytochemical analysis, determination of beta2-microglobulin (β2-m), neuron-specific enolase, and CMV DNA detection. Neuroimaging was classified according to a validated scoring system comprising calcifications, ventriculomegaly, and atrophy, with findings graded from 0 to 3. Systematic long-term neurodevelopmental assessment included motor function, cognition, behavior, hearing, vision, and epilepsy. Sequelae were graded as mild/absent, moderate, or severe; adverse outcome was defined as death or moderate to severe disability. Three children died. The mean age at follow-up of the survivors was 8.7 ± 5.3 years (range, 19 months to 18.0 years). Neonatal findings showing a significant association with adverse outcome were relative microcephaly, CSF β2-m concentrations, and grade 2-3 neuroimaging abnormalities (P < .05). Receiver operator characteristic curve analysis indicated that the most accurate single factor for predicting unfavorable outcome was CSF β2-m>7.9 mg/L (area under the curve, 0.84 ± 0.08; sensitivity, 69%; specificity, 100%). The combination of CSFβ2-m >7.9 mg/L and moderate-severe neuroimaging alterations improved predictive ability (area under the curve, 0.92 ± 0.06; sensitivity, 87%; specificity, 100%). Adjusted head circumference, CSF β2-m level, and neuroimaging studies have prognostic significance for neurodevelopmental outcome in newborns with congenital CMV. A combination of early findings improves the predictive value.

A Case of Delayed-onset Sensorineural Hearing Loss with Congenital Cytomegalovirus Infection

Sensorineural hearing loss (SNHL) due to congenital cytomegalovirus (CMV) infection can either be present at birth or develop later in life. We report a 3 years 7 months old boy who gradually developed speech until 3 years of age, but later showed no responses to verbal stimuli. He was first referred to our clinic for the evaluation of motor delay at 9 months of age and was found to have left hemiparesis. Brain MRI revealed polymicrogyria in the right frontal region. Epileptic seizures began at the age of 13 months. Verbal development was assessed annually using intellectual function testing. He responded to his name at 9 months of age, and imitated words and pointed to objects when asked at 21 months. He could speak several words at 34 months of age. However, around 3 years of age, he stopped saying meaningful words. Audiologic evaluation revealed severe SNHL at 3 years 7 months old. There was no family history of hearing loss, past medical history of ototoxic medications or bacterial meningitis, or craniofacial/auditory anomalies, as possible factors related to the hearing loss. At the age of 7 years 5 months, examination of a dried umbilical cord specimen revealed the presence of CMV DNA. Thus, this patient was diagnosed as having delayed-onset SNHL with asymptomatic congenital CMV infection. A prospective study is necessary for early detection of delayed-onset SNHL in patients with asymptomatic congenital CMV infection. Testing for the presence of CMV DNA in neonatal urine is performed in cases in which pregnant women are seronegative for CMV-IgG antibody or seropositive for CMV-IgM antibody during the first trimester of pregnancy. Infants diagnosed as having congenital CMV infection are evaluated by a newborn hearing screening test, head CT, ophthalmologic evaluations, and intellectual function testing. Follow-up hearing assessments are performed by both the auditory brainstem response and behavioral audiometry.

Prevalence of Cytomegalovirus DNA in Cord Blood and Voided Urine Obtained from Pregnant Women at the End of Pregnancy

Objective: This study was undertaken to determine the prevalence of congenital cytomegalovirus (CMV) infection in pregnant women at the end of pregnancy in Kuwait using cord blood and maternal urine. Subjects and Methods: Urine samples were collected prior to childbirth, and cord blood was collected immediately after delivery from 983 women. Anti-CMV IgG and IgM antibodies were determined using ELISA; CMV DNA was detected using nested PCR, and viral load was calculated using real-time PCR. CMV concentration in samples was categorized as low when the viral load ≤10³ copies/µl, intermediate when the viral load = 10³–10⁴ copies/µl, and high when the viral load >10⁴ copies/µl. The cord blood serology outcome was compared to cord blood PCR, cord blood viral load, maternal urine PCR and viral load analyses. Results: Serology showed that of the 983 cord blood samples, 89 (9%) were positive for anti-CMV IgM antibodies; PCR test showed 44 (4.5%) contained CMV DNA, and there was a high viral load in all. Maternal urine PCR showed that 9 (10.11%) women had CMV DNA, and there was a high viral load in 7 (78%). The kappa test for measures of agreement showed a reasonable agreement (0.45) between cord blood PCR and urine PCR. Conclusion: This study showed that CMV infection in the cord blood sera of pregnant women is common in Kuwait and highlights the need for more clinically based studies to follow up newborns with congenital CMV infection.

Congenital cytomegalovirus infection – a common cause of hearing loss of unknown aetiology

The aim of this study was to investigate the role of congenital cytomegalovirus (CMV) infection as a cause of various types of sensorineural hearing loss (SNHL) in a group of nonsyndromic children with otherwise unknown aetiology of hearing loss. Furthermore, the occurrence of combined congenital CMV infection and connexin 26 (Cx26) mutations was investigated. The dried blood spot (DBS) cards of 45 children with various degrees of hearing deficits and 46 children with severe/profound hearing loss were tested for CMV DNA with polymerase chain reaction (PCR) technique. The DBS cards of the 46 children with severe/profound hearing loss were also analysed for Cx26 mutations. Of the 45 children with various degrees of hearing loss, nine were positive for CMV DNA (20%). The nine children represented severe/profound, mild and unilateral hearing loss. From the 46 children with severe/profound hearing loss, nine of 46 (20%) were positive for CMV DNA. In addition, three of the CMV DNA-positive children were carriers of mutations of Cx26. Congenital CMV infection is a high risk factor in hearing impairment among children.