Congenital Cytomegalovirus Disease Research Articles

Properties and Mechanisms of Immunoglobulins for Congenital Cytomegalovirus Disease

Immunoglobulins are one major component of adaptive immunity to external and resident microorganisms, evolving very early in phylogenesis. They help eukaryotes in controlling infections, mainly through their neutralizing activity, which quenches both the cytopathic and inflammatory potential of invading microorganisms. Cytomegalovirus (CMV)-related disease is generally blunted in seropositive subjects with conserved specific humoral responses. CMV-seropositive pregnant women, in accordance with such evidence, suffer little or no fetal damage when reexposed to CMV. Several seminal experiences and early experimental models confirmed that repeated infusions of immunoglobulins, either with hyperimmune or standard preparations, may help to reduce maternal-fetal CMV transmission, as well as to quench fetal disease upon transmission. This review focused on experimental evidence supporting the potential role of immunoglobulins as a tool to control fetal CMV-related disease in pregnant women.

Cytomegalovirus infection among infants in California neonatal intensive care units, 2005–2010

To assess the burden of congenital and perinatal cytomegalovirus (CMV) disease among infants hospitalized in neonatal intensive care units (NICUs). CMV infection was defined as a report of positive CMV viral culture or polymerase chain reaction at any time since birth in an infant hospitalized in a NICU reporting to California Perinatal Quality Care Collaborative during 2005-2010. One hundred and fifty-six (1.7 per 1000) infants were reported with CMV infection, representing an estimated 5% of the expected number of live births with symptomatic CMV disease. Prevalence was higher among infants with younger gestational ages and lower birth weights. Infants with CMV infection had significantly longer hospital stays and 14 (9%) died. Reported prevalence of CMV infection in NICUs represents a fraction of total expected disease burden from CMV in the newborn period, likely resulting from underdiagnosis and milder symptomatic cases that do not require NICU care. More complete ascertainment of infants with congenital CMV infection that would benefit from antiviral treatment may reduce the burden of CMV disease in this population.

Polymorphisms in TLR-2 are associated with congenital cytomegalovirus (CMV) infection but not with congenital CMV disease

Cytomegalovirus (CMV) is the most common cause of congenital virus infection. However, the risk factors for infection in utero and for progression to a severe clinical outcome remain uncertain. Recent studies have identified associations of specific single nucleotide polymorphisms (SNPs) in Toll-like receptor (TLR) genes with susceptibility to infections of some viruses and with their clinical outcome. Genetic polymorphisms in the TLR-2, TLR-4, and TLR-9 genes were analyzed in 87 children with congenital CMV infections by the TaqMan allelic discrimination assay. The frequencies of genotypes in the general Japanese population were obtained from the National Center for Biotechnology Information (NCBI) databases. Associations between the analyzed SNPs and congenital CMV infection or disease were evaluated. The CC genotype at SNP rs3804100 in the TLR-2 gene was significantly associated with congenital CMV infection but not with congenital CMV disease. Furthermore, the AG genotype at SNP rs1898830 in the TLR-2 gene tended to be identified less frequently in children with congenital CMV infection. There were no statistically significant associations between SNPs in the TLR-4 and TLR-9 genes and congenital CMV infection or disease. TLR-2 polymorphisms may have some association with congenital CMV infection, although the mechanism underlying this effect remains to be clarified.

Cytomegalovirus in pregnancy: to screen or not to screen.

BackgroundCytomegalovirus (CMV) infection is now the commonest congenital form of infective neurological handicap, recognized by the Institute of Medicine as the leading priority for the developed world in congenital infection. In the absence of an effective vaccine, universal screening for CMV in pregnancy has been proposed, in order that primary infection could be diagnosed and- potentially- the burden of disability due to congenital CMV prevented.DiscussionUniversal screening for CMV to identify seronegative women at the beginning of pregnancy could potentially reduce the burden of congenital CMV in one of three ways. The risk of acquiring the infection during pregnancy has been shown to be reduced by institution of simple hygiene measures (primary prevention). Among women who seroconvert during pregnancy, CMV hyperimmune globulin (CMV HIG) shows promise in reducing the risk of perinatal transmission (secondary prevention), and CMV HIG and/ or antivirals may be effective in reducing the risk of clinical sequelae among those known to be infected (tertiary prevention). The reports from these studies have re-ignited interest in universal screening for CMV, but against the potential benefit of these exciting therapies needs to be weighed the challenges associated with the implementation of any universal screening in pregnancy. These include; the optimal test, and timing of screening, to maximize detection; an approach to the management of equivocal results, and the cost effectiveness of the proposed screening program. In this article, we provide an overview of current knowledge and ongoing trials in the prevention, diagnosis and management of congenital CMV. Recognising that CMV screening is already being offered to many patients on an ad hoc basis, we also provide a management algorithm to guide clinicians and assist in counseling patients.SummaryWe suggest that- on the basis of current data- the criteria necessary to recommend universal screening for CMV are not yet met, but this position is likely to change if trials currently underway confirm that CMV HIG and/ or antivirals are effective in reducing the burden of congenital CMV disease.

Long-term Outcomes of Congenital Cytomegalovirus Infection in Sweden and the United Kingdom

Congenital cytomegalovirus (CMV) is an important cause of neurological problems, particularly sensorineural hearing loss, but data on long-term sequelae and the impact of nonprimary maternal infection are limited. We report updated findings on childhood outcomes from 2 large prospective studies. Pregnant women in Malmö, Sweden, and London, United Kingdom, were included between 1977 and 1986, and newborns were screened for CMV (virus culture of urine or saliva). Cases and matched controls underwent regular, detailed developmental assessments up to at least age 5 years. One hundred seventy-six congenitally infected infants were identified among >50 000 screened (Malmö: 76 [4.6/1000 births]; London: 100 [3.2/1000 births]); 214 controls were selected. Symptoms were recorded in 11% of CMV-infected neonates (19/176) and were mostly mild; only 1 neonate had neurological symptoms. At follow-up, 7% of infants (11/154) were classified as having mild, 5% (7/154) moderate, and 6% (9/154) severe neurological sequelae. Four of 161 controls (2%) had mild impairment. Among children symptomatic at birth, 42% (8/19) had sequelae, versus 14% (19/135) of the asymptomatic infants (P = .006). All moderate/severe outcomes were identified by age 1; mild sequelae were first identified at age 2-5 years in 6 children, and age 6-7 years in 3. Among the 16 children with moderate/severe outcomes, 2 had mothers with confirmed and 7 with presumed nonprimary infection. Moderate or severe outcomes were reported in 11% of children with congenital CMV identified through population screening, all by 1 year; all impairment detected after this age was mild. Nonprimary infections contributed substantially to the burden of childhood congenital CMV disease.

Fetal hyperechogenic bowel may indicate congenital cytomegalovirus disease responsive to immunoglobulin therapy

Objective: To determine whether fetal hyperechogenic bowel is associated with a poor outcome with or without immunoglobulin therapy. Methods: Sixteen pregnant women whose 17 fetuses had hyperechogenic bowel were followed by a protocol of offering additional serologic testing, amniocentesis, hyperimmunoglobulin (HIG), serial ultrasounds, and evaluation of their children. Results: Of 17 fetuses with hyperechogenic bowel, 13 showed hyperechogenic bowel as a single or first ultrasound sign compared to four who showed it concomitantly or after other ultrasound abnormalities appeared (P = 0.02). Of the 17 fetuses with hyperechogenic bowel, nine were treated with HIG. Eight of the nine were normal at birth and during a follow-up of 3–8 years. One treated fetus is deaf at 4 years of age. A significantly different result (P < 0.0004) occurred among seven untreated fetuses who were each severely affected at 2–7 years of age, and the remaining one died soon after preterm birth. Among seven of nine fetuses (77.8%) of treated mothers the fetal hyperechogenic bowel resolved after HIG administration. There were no significant differences between treated and untreated fetuses for gestational age at maternal infection, gestational age at birth, and birth weight. Conclusion: Hyperechogenic bowel may be a marker of congenital cytomegalovirus (CMV) disease, which may be prevented by HIG.

Use of cytomegalovirus hyperimmunoglobulin for prevention of congenital cytomegalovirus disease: a retrospective analysis

The aim of this study was to investigate the current prenatal "off-label use" of cytomegalovirus hyperimmunoglobulin (CMV-HIG) in the prevention and treatment of congenital CMV (cCMV) infection, including the long-term outcome of the children. This retrospective observational study comprised mothers and their children, born between January 1, 2006, and October 30, 2010. Prenatal CMV-HIG was administered after diagnosis of primary CMV infection of the mother. Clinical and virological data were collected from maternal and pediatric medical and laboratory reports. Follow-up was 12-36 months after birth. Forty-two women and 43 children met the study criteria. In total, 40 mothers and six unborn infants received 115 doses of CMV-HIG. The treatment group (TG; CMV-DNA polymerase chain reaction-positive amniotic fluid) included four mothers; the multinomial group (MG; CMV-positive mother and unknown CMV status of fetus) included 38 mothers (39 infants). For the four unborn infants in TG, CMV-HIG was administered either intraumbilically or into the amniotic fluid; three of the four mothers received intravenous CMV-HIG. Three children in TG remained CMV-positive and were asymptomatic at birth and during follow-up. One infant in TG had symptomatic cCMV infection in utero, at birth, and during follow-up. In MG, 37 of 38 women received intravenous CMV-HIG and two of 39 infants received CMV-HIG in utero. In total, 9 (23.1%) of 39 children in MG were positive for cCMV (including a terminated pregnancy). All eight instances of cCMV infection at birth in MG were asymptomatic at birth and during follow-up. The fetus from the terminated pregnancy showed no sonographic symptoms of cCMV infection. No severe side effect occurred in 115 CMV-HIG applications. CMV-HIG was well tolerated. Compared with published untreated mother-child pairs, we observed a trend toward a smaller risk for intrauterine CMV transmission following CMV-HIG application. Signs of prenatal cCMV disease were not reversed after CMV-HIG.

Mycotic Aneurysm and Subarachnoid Hemorrhage Following Tubercular Meningitis in an Infant With Congenital Tuberculosis and Cytomegalovirus Disease

We describe autopsy findings in a 5-month-old infant with disseminated tuberculosis and congenital cytomegalovirus disease. The infant manifested with tubercular meningitis complicating as ruptured mycotic right middle cerebral artery aneurysm. Infiltrative, proliferative, and necrotizing vascular pathologies have been described; however, the occurrence of these is dependent on the duration of illness. The vessel pathology appears to be a payback of its immersion in the local inflammatory cell-rich exudates. Strokes early in the course of the disease are believed to be a consequence of vasospasm, and those occurring later during the disease course are due to proliferative intimal disease. Intracranial mycotic aneurysm following tubercular meningitis developing at such a young age has not been reported in the literature. The lung lesions in a congenitally transmitted tuberculosis and cytomegalovirus disease have also been elaborated.

Congenital Cytomegalovirus Infection: Molecular Mechanisms Mediating Viral Pathogenesis

Human cytomegalovirus (CMV) is responsible for approximately 40,000 congenital infections in the United States each year. Congenital CMV disease frequently produces serious neurodevelopmental disability, as well as vision impairment and sensorineural hearing loss. Development of a CMV vaccine is therefore considered to be a major public health priority. The mechanisms by which CMV injures the fetus are complex and likely include a combination of direct fetal injury induced by pathologic virally-encoded gene products, an inability of the maternal immune response to control infection, and the direct impact of infection on placental function. CMV encodes gene products that function, both at the RNA and the protein level, to interfere with many cellular processes. These include gene products that modify the cell cycle; interfere with apoptosis; induce an inflammatory response; mediate vascular injury; induce site-specific breakage of chromosomes; promote oncogenesis; dysregulate cellular proliferation; and facilitate evasion of host immune responses. This minireview summarizes current concepts regarding these aspects of the molecular virology of CMV and the potential pathogenic impact of viral gene expression on the developing fetus. Areas for potential development of novel therapeutic intervention are suggested for improving the outcome of this disabling congenital infection.

Revisión y recomendaciones sobre la prevención, diagnóstico y tratamiento de la infección posnatal por citomegalovirus

Postnatal cytomegalovirus (CMV) infection in the newborn can occur from exposure to maternal cervical secretions during birth, ingestion of breast milk, transfusion of blood products or transmission by body fluids of infected people. Breast milk is the main source of infection, given the high rate of CMV-positive mothers excreting CMV in milk. Freezing reduces the risk of CMV transmission by breastfeeding, although it does not eliminate it completely. Pasteurisation prevents such transmission, but it can alter the immunological properties of breast milk. Postnatal CMV infection is usually asymptomatic, as it normally results from viral reactivation in the mother, and the neonate is born with protective antibodies. However, in the very low birth weight premature infant the amount of transferred antibodies is smaller and a symptomatic infection can occur. Symptomatic posnatal CMV infection in the newborn typically causes hepatitis, neutropenia, thrombocytopenia or sepsis-like syndrome. Pneumonitis and enteritis are less common, but very characteristic. Diagnosis is based on urine virus detection at the time of onset of symptoms. Postnatal CMV infection in the newborn generally resolves spontaneously without antiviral treatment. Ganciclovir should be reserved for severe cases. Unlike congenital CMV disease, posnatal CMV infection in the preterm infant does not seem to be associated with hearing loss or abnormal neuro-development in long term follow-up.

Effect on Hearing of Oral Valganciclovir for Asymptomatic Congenital Cytomegalovirus Infection

Congenital cytomegalovirus (CMV) infection is the leading nongenetic cause of congenital sensorineural hearing loss (SNHL). Hearing loss due to congenital CMV infection either has onset after the newborn period or shows progressive decline in auditory thresholds. Although 90% of the congenitally infected infants are asymptomatic at birth, evidence is accumulating that these infants are at risk for audiologic, neurologic and developmental sequelae. In symptomatically infected infants, ganciclovir therapy administered in the neonatal period prevents hearing deterioration. However, preventative therapy of asymptomatic congenital CMV disease is controversial. Here in, we reported a male newborn with asymptomatic congenital CMV with bilateral SNHL. Oral treatment with valganciclovir in patient resulted in progressive improvement of SNHL, which effectively reduced the CMV viral load and was well tolerated without apparent adverse effects.

Citomegalovirus congénito: ¿es necesario un cribado serológico durante el embarazo?

Primary cytomegalovirus (CMV) infection occurs during pregnancy in 1% to 4% of seronegative women and may be transmitted to the fetus in up to 40% of cases. Up to 10% of intrauterine CMV infections result in symptomatic congenital disease at birth. Half of these children and 13% of those born with asymptomatic infection will develop significant clinical sequelae in infancy, especially sensorineural hearing loss. Routine CMV screening during pregnancy is not recommended in Spain owing to the absence of an effective CMV vaccine, the lack of preventive measures or therapy during pregnancy, the difficulty in diagnosing a reactivated infection, and the possibility of symptomatic congenital infections in children of immune women. However, sensitive and specific methods to diagnose primary maternal and fetal infection now exist, and new preventive and therapeutic measures have been developed. Currently, these procedures are not universally available and need to be tested in larger trials. Furthermore, the prevalence of seropositive status in pregnant women, the frequency of congenital infection, and the percentage of infants born with hearing impairment and mental retardation in our country are not known. Therefore, it would not be appropriate to introduce routine screening for CMV in pregnancy at the present time. However, increased efforts should be made to inform women about congenital CMV disease, to develop the diagnosis of fetal infection and methods to determine the extent of involvement in the case of suggestive ultrasound findings, and to treat symptomatic infected newborns with antivirals to reduce hearing impairment.

Screening Newborns for Congenital Cytomegalovirus Infection

IN THIS ISSUE OF JAMA, BOPPANA AND COLLEAGUES 1 DEscribe their attempts to validate universal screening methods for congenital cytomegalovirus (CMV) infection, the most common congenital viral infection in the United States and many other regions, by using polymerase chain reaction (PCR) analysis of newborn dried blood spots. Congenital CMV infection remains an important public health problem not only because it has accounted for as much or more disability over the past 50 years than was associated with congenital rubella syndrome, but also because CMV infection, whether symptomatic or silent at birth, represents the most common nongenetic cause of permanent hearing loss among children in the United States. Congenital CMV infection causes a substantial proportion of sensorineural hearing loss even in regions with a low prevalence. Culture surveillance of nearly 4000 newborns in Utah revealed a congenital infection rate of 0.29%, corresponding to approximately 3 infected infants for every 1000 newborns or 165 infected newborns annually statewide, given the state’s current birth rate. Because as many as 10% of these infants will have CMV disease, a condition associated with a 30% to 50% prevalence of sensorineural hearing loss, and the remainder will have silent CMV infection, a condition conservatively associated with a 6% to 8% rate of sensorineural hearing loss, CMV accounts for hearing loss in 15 to 20 children each year in Utah, or approximately 20% of the 90 to 120 Utah children identified with permanent hearing loss annually (J. C. Carey, University of Utah School of Medicine, written communication, March 2010). Worldwide, thousands of infants have CMV-induced hearing loss annually. Universal newborn screening for many disorders has immense public health benefits. The history of phenylketonuria (PKU) illustrates the enormous benefit of such strategies. Universal screening of newborn hearing has led to improvement in language outcomes, with greater improvements when deaf infants are identified earlier and interventions are begun sooner. Thus, it seems logical to infer that if CMV-infected infants can be identified in the neonatal period, hearing could be tracked closely, interventions could begin early, and the hearing outcomes of congenital CMV infection might be improved. However, 2 challenges confront universal screening for congenital CMV infection. First, universal screening is only justified when an effective intervention exists that prevents adverse health outcomes, such as averting intellectual disability when infants who lack phenylalanine hydroxylase initiate a diet low in phenylalanine early in life. At present, no such solution exists for CMV. Although neonatal ganciclovir therapy improves hearing outcomes in some infants, the benefits are not universal and the risk/benefit ratio of ganciclovir therapy in infants with silent congenital CMV infection has not been sufficiently well-established to recommend such therapy for all CMV-infected infants. Nonetheless, knowing which infants are infected with CMV has benefit through early identification of infants at risk of CMVinduced hearing loss and may have additional benefits in the future when new and more effective antiviral strategies become available. The second challenge, the one addressed by Boppana et al, is the availability of a highly sensitive and specific screening method. Neonatal screening of hearing alone is insufficient to detect all CMV-infected infants because most infants with congenital CMV infection have normal hearing in the neonatal period. Fowler et al demonstrated that nearly 20% of the children with hearing loss due to silent congenital CMV infection have delayed onset of sensorineural hearing loss. In addition, most infants with congenital hearing loss do not have CMV infection. In 1996, when Barbi et al demonstrated that newborn dried blood spots and PCR assays could be used to detect CMV DNA in the blood of congenitally infected infants, there was optimism that the opportunity for universal screening for CMV had arrived. However, the study by Barbi et al was not population-based and did not have a sufficient sample size to establish convincingly the sensitivity and specificity of mass screening of newborn dried blood spots. In contrast, the large, prospective study by Boppana et al shows that even though real-time PCR has excellent specificity (approaching 100%), the sensitivity of the PCR

Neurodevelopmental outcomes following ganciclovir therapy in symptomatic congenital cytomegalovirus infections involving the central nervous system

Background Ganciclovir protects against hearing deterioration in infants with symptomatic congenital cytomegalovirus (CMV) disease involving the central nervous system (CNS). Objectives To assess the neurodevelopmental impact of ganciclovir therapy in this population. Study design 100 neonates were enrolled into a controlled Phase III study of symptomatic congenital CMV involving the CNS, and were randomized to either 6 weeks of intravenous ganciclovir or no treatment. Denver developmental tests were performed at 6 weeks, 6 months, and 12 months. For each age, developmental milestones that ≥90% of normal children would be expected to have achieved were identified. The numbers of milestones not met (“delays”) were determined for each subject. The average number of delays per subject was compared for each treatment group. Results At 6 months, the average number of delays was 4.46 and 7.51, respectively, for ganciclovir recipients and “no treatment” subjects ( p = 0.02). At 12 months, the average number of delays was 10.06 and 17.14, respectively ( p = 0.007). In a multivariate regression model, the effect of ganciclovir therapy remained statistically significant at 12 months ( p = 0.007). Conclusions Infants with symptomatic congenital CMV involving the CNS receiving intravenous ganciclovir therapy have fewer developmental delays at 6 and 12 months compared with untreated infants. Based on these data as well as the previously published data regarding ganciclovir treatment and hearing outcomes, 6 weeks of intravenous ganciclovir therapy can be considered in the management of babies with symptomatic congenital CMV disease involving the CNS. If treatment is initiated, it should be started within the first month of life and patients should be monitored closely for toxicity, especially neutropenia. Since existing data only address the treatment of symptomatic congenital CMV disease involving the CNS, these data cannot be extrapolated to neonates with other manifestations of CMV disease, including asymptomatic babies and symptomatic babies who do not have CNS involvement.

Birth Prevalence and Natural History of Congenital Cytomegalovirus Infection in a Highly Seroimmune Population

The natural history of congenital cytomegalovirus (CMV) infection is scarcely known in populations with high maternal CMV seroprevalence. This study evaluated the birth prevalence, clinical findings at birth, and hearing outcome in CMV-infected children from such a population. Consecutively born infants were screened for the presence of CMV in urine and/or saliva specimens during the first 2 weeks after birth. Neonatal clinical findings were recorded, and CMV-infected children were tested to document hearing function during follow-up. A subset of mothers of CMV-infected infants were prenatally tested for the presence of anti-CMV immunoglobulin G antibodies. Congenital CMV infection was confirmed in 87 (1.08%; 95% confidence interval [CI], 0.86%-1.33%) of 8047 infants. Seven infants (8.1%; 95% CI, 3.3%-15.9%) had at least 1 clinical finding suggestive of CMV infection, and 4 (4.6%; 95% CI, 1.3%-11.3%) had >3 findings of systemic disease. Sensorineural hearing loss was found in 5 (8.6%; 95% CI, 2.9%-19.0%) of 58 children tested at a median age of 21 months. Bilateral profound hearing loss was observed in 2 children, and the hearing threshold was >60 decibels in all 5 children with hearing loss, including 2 children born to mothers with probable nonprimary CMV infection. The results of this large newborn screening study in a population with high CMV seroimmunity provide additional evidence that congenital CMV disease occurs in populations with high seroprevalence rates, with a similar incidence of CMV-related hearing loss to that reported in the offspring of women from populations in developed countries with lower rates of seroimmunity to CMV.

Guidelines on CMV congenital infection

Congenital cytomegalovirus (CMV) infection occurs in 0.6-0.7% of all newborns and is the most prevalent infection-related cause of congenital neurological handicap. Vertical transmission occurs in around 30% of cases, but the fetus is not always affected. Symptomatic newborns at birth have a much higher risk of suffering severe neurological sequelae. Detection of specific IgG and IgM and IgG avidity seem to be the most reliable tests to identify a primary infection but interpretation in a clinical context may be difficult. If a seroconversion is documented or a fetal infection is suspected by ultrasound markers, an amniocentesis should be performed to confirm a vertical transmission. In the absence of a confirmed fetal infection with fetal structural anomalies, a pregnancy termination should be discouraged. Fetal prognosis is mainly correlated to the presence of brain damage. Despite promising results with the use of antiviral drugs and CMV hyperimmune globulin (HIG), results have to be interpreted with caution. Pregnant women should not be systematically tested for CMV during pregnancy. Managing CMV screening should be restricted to pregnancies where a primary infection is suspected or among women at high risk. The magnitude of congenital CMV disease and the value of interventions to prevent its transmission or to decrease the sequelae need to be established before implementing public health interventions. In this paper, aspects of CMV infection in the pregnant woman and her infant are reviewed.

Epidemiological impact and disease burden of congenital cytomegalovirus infection in Europe

In Europe, congenital cytomegalovirus (CMV) infection is the leading cause of neurological disabilities in children, causing severe sequelae such as sensorineural hearing loss, neurodevelopmental delay or blindness. The infection causes high disease burden and costs. Nevertheless, there is little awareness of CMV among medical officials and the general public.

Trends in hospitalizations for diagnosed congenital cytomegalovirus in infants and children in Australia

BackgroundCytomegalovirus (CMV) is responsible for a wide range of diseases in neonates, and has been recognized as a major cause of congenital defects in developed countries for many years. More children suffer serious disabilities caused by congenital CMV than by several better-known childhood maladies. Insight into the epidemiology of congenital CMV disease is needed for the assessment of preventive strategies.MethodsUsing data from the National Hospital Morbidity Database (NHMD) complied by the Australian Institute of Health and Welfare (AIHW), we examined the rates of hospital admissions for children diagnosed with congenital cytomegalovirus (CMV) by year, sex, age group and length of stay.ResultsOver an 8-year period (1993–2001), there were 1314 admissions for the congenital form of CMV disease. Of these admissions, 25% were principally hospitalized because of congenital CMV. The average annual rate of admissions in children aged 0–4, 5–9 and 10–14 years was 9.40, 2.40 and 0.85 per 100,000 Australian population respectively.ConclusionCompared with many other congenital illnesses, which are now vaccine preventable, the burden of congenital CMV is comparatively high. A vaccination program would be justifiable should a vaccine become available.

Effect on hearing of ganciclovir therapy for asymptomatic congenital cytomegalovirus infection: four to 10 year follow up

Congenital cytomegalovirus infection is the leading identified nongenetic cause of congenital sensorineural hearing loss. Most of the infections are asymptomatic but may be detected from umbilical cord vein and/or newborn serum positivity for human cytomegalovirus immunoglobulin M, and from urine positivity (on polymerase chain reaction) for human cytomegalovirus deoxyribonucleic acid in the newborn period. Children infected by cytomegalovirus may later develop sensorineural hearing loss. In symptomatically infected infants, ganciclovir therapy administered in the neonatal period prevents hearing deterioration. However, preventative therapy of asymptomatic congenital cytomegalovirus disease with ganciclovir is controversial, as side effects such as severe neutropenia may occur during treatment. The study population consisted of 23 asymptomatic children with congenital cytomegalovirus infection. Twelve children were treated just after diagnosis of cytomegalovirus infection in the newborn period, with ganciclovir 10 mg/kg bodyweight for 21 days. The other 11 children were observed without therapy. Over a four to 10 year follow-up period, we evaluated all the children's hearing status using pure tone audiometry. All 23 children had normal sensorineural hearing at one year follow up. Five of the 23 children (21.7 per cent) were lost to follow up over the four to 11 year follow-up period. Of the remaining 18 children, sensorineural hearing loss occurred in two (11.1 per cent). Neither child had been treated with ganciclovir in the newborn period. An eight-year-old boy showed bilateral high frequency loss and a 10-year-old girl showed severe unilateral sensorineural hearing loss. In the ganciclovir-treated group (nine children), none showed sensorineural hearing loss. During ganciclovir therapy, moderate neutropenia occurred as a side effect in two out of 12 (16.6 per cent) treated children. Speech and general development were normal in all children. Asymptomatic congenital cytomegalovirus infection is likely to be a leading cause of sensorineural hearing loss in young children. Intravenous ganciclovir therapy seems to offer a medical option to prevent subsequent sensorineural hearing loss. Further studies including a greater number of children are needed. Cytomegalovirus screening models are mandatory if medical therapy is to be implemented in time.

Congenital cytomegalovirus infection: Update on management strategies

Congenital cytomegalovirus (CMV) infections are underrecognized as a cause of serious morbidity in newborn infants. The era of therapeutic nihilism regarding these infections has come to an end, however, as useful therapies are now available that may modify the outcome. The infected fetus can be treated in utero, or the newborn infant can be treated when CMV is recognized in the neonatal period. Expanded screening of newborns for congenital CMV infection will make it even more important for clinicians to be aware of current therapeutic options. The most effective option for the treatment of life-threatening or sight-threatening CMV disease at any age is the nucleoside analog ganciclovir. For the newborn with congenital CMV infection, the value of ganciclovir appears to relate to its ability to preserve hearing; other improvements in overall neurodevelopmental status are inferred but remain to be proven. In the pregnant woman with primary CMV infection, the use of CMV-specific immune globulin, though still investigational, is garnering attention and may prove to be a valuable therapy.