Urine polymerase chain reaction as a screening tool for the detection of congenital cytomegalovirus infection

OBJECTIVES: To define the incidence of congenital cytomegalovirus (CMV) infection in a defined population in Israel as diagnosed by urine polymerase chain reaction (PCR), and to assess the utility of this method for screening for congenital CMV infection. DESIGN: A convenient sample of urine specimens from asymptomatic newborns were subjected to CMV PCR. Positive results were validated by urine tube culture and by determination of serum CMV IgM antibodies. Maternal CMV IgG was determined in a representative sample of mothers. Newborns with positive urine specimens underwent full clinical evaluation. Epidemiological characteristics of the mothers were extracted from the medical records. SETTINGS: Two medical centres in Israel with different population characteristics. PATIENTS: A total of 2000 newborns (1000 in each medical centre). MAIN OUTCOME MEASURE: Presence of CMV DNA in the urine. RESULTS: Despite significant epidemiological differences between the populations in the two hospitals, the CMV seroprevalence was similar, 80.5% and 85%. Fourteen of the 2000 newborns screened (0.7%) were PCR positive. Urine culture was positive in nine of 10 specimens; IgM was positive in only two of 13 newborns with positive PCR. Eleven newborns underwent full or partial evaluation, and only one (9%) was symptomatic. CONCLUSIONS: The incidence of congenital CMV infection in the study population was 0.7%; over 90% were asymptomatic. Urinary CMV PCR is a reliable, rapid, and convenient method, and thus may serve as a screening tool for the detection of congenital CMV infection.     

北京地区新生儿先天巨细胞病毒感染状况研究

目的评估北京地区新生儿先天性巨细胞病毒(CMV)感染状态及其对新生儿的危害。方法选择2004年11月至2008年3月在北京居住、怀孕12周之内的孕妇,分别于孕早期和孕中期进行血清CMV IgG定量和CMV IgM定性检测;活动感染者接受CMV IgG亲和力、CMV pp65抗原血症和白细胞CMV巢式聚合酶链反应(nPCR)检测;白细胞CMV DNA阳性孕妇接受羊水CMV nPCR检测。所有入选孕妇分娩的新生儿出生后均检测脐血CMV nPCR,阳性者于生后2周内复查尿CMV nPCR。结果本研究共收入孕妇1752例,新生儿1756例;孕期血清学检查CMV活动感染51例,占2.91%(95%CI 2.12%～3.70%),其中原发活动感染2例,占全部孕妇的0.11%(95%CI 0.10%～0.41%);CMV nPCR阳性的孕期活动性感染占0.34%;活动感染孕妇羊水CMV nPCR检测全部阴性;新生儿先天性CMV感染发生率0.23%(95%CI 0.06%～0.58%)。所有先天性CMV感染新生儿出生时均为无症状性感染。结论北京地区CMV感染垂直传播率低,先天CMV感染发生率0.23%,未见到症状性先天性CMV感染患儿。     

Beta2-microglobulin concentrations in cerebrospinal fluid correlate with neuroimaging findings in newborns with symptomatic congenital cytomegalovirus infection

Overview In newborns with symptomatic congenital cytomegalovirus (CMV) infection, neuroimaging is the best available predictor of neurodevelopmental outcome. Cerebrospinal fluid (CSF) findings in congenital CMV infection have seldom been described. Neonates with central nervous system infections present high CSF Beta₂-microglobulin (β₂-m) levels.Objectives The objectives of this study were: (1) to determine whether CSF β₂-m is increased in newborns with symptomatic congenital CMV infection, and (2) to examine its correlation with neuroimaging findings.Materials and methods Fourteen newborns with symptomatic congenital CMV infection admitted to La Paz Hospital from 1990 through 2004 underwent determination of CSF β₂-m. Ninety-three newborns, constituting the comparison group, underwent CSF β₂-m determination as part of a sepsis or meningo/encephalitis work-up, and at discharge had sterile cultures and normal neurological status. Neuroimaging findings were scored according to a semiquantitative system: (0) no abnormalities; (1) single punctate periventricular (PV) calcification and/or hyperechogenic areas in the thalamus and basal ganglia; (2) multiple discrete PV calcifications and/or ventriculomegaly; and (3) extensive PV calcifications and/or brain atrophy.Discussion and conclusion CSF β₂-m was increased in newborns with CMV infection (median 6.21 mg/L) compared with controls (1.68 mg/L) (P<.001). β₂-m showed a correlation with neuroimaging scores (r _s=0.753, P=.002). β₂-m was higher in patients who scored 2–3 (12.83 mg/L) than in patients who scored 0–1 (5.52 mg/L) (P=.028). CSF β₂-m is increased in newborns with symptomatic congenital CMV infection and correlates with neuroimaging abnormalities. β₂-m appears to be an indicator of the severity of brain involvement in congenital CMV infection.     

Congenital cytomegalovirus infection

The cytomegalovirus (CMV) is responsible for the most common congenital infection and represents the most important cause of mental disability and non hereditary sensorineural deafness in infants. One percent to 5% of women show symptoms of infection during pregnancy. Forty thousand newborns are affected by this infection in the United States every year, at a cost of 1.9 billion dollars; in Italy, approximately 5,500 infected newborns are expected each year, including 350 in Lombardia alone. In 90% of the cases, the infected newborns present no symptoms at birth, but, in 10% to 15% of these cases, they are not immune to future manifestations of the infection. Ten percent of newborns with congenital infection, however, show symptoms that lead to a strongly unfavourable prognosis. The authors describe the most important pre and post natal diagnostic findings and emphasize the importance of counseling in this pathology. They also point out the least frequent clinical manifestations of the infection in newborns, which can cause problems of differential diagnosis. In light of the most recent literary data, the article outlines the most recent therapeutic schemes as well as their effectiveness. Lastly, the authors discuss the sequels of the congenital infection, which can present themselves in infected newborns even after a long period of time. This corresponds to one of the most important aspects of the topic and the authors propose a follow-up program that applies to those children until the age of 6. There is currently no effective or safe vaccine for the CMV, therefore hygienic-health measures constitute the principal form of prevention of the CMV congenital infection, which represents a significant problem for newborns, their families, and society.     

Congenital cytomegalovirus infection: outcome and diagnosis

Cytomegalovirus (CMV) is the most common congenital infection in humans and an important cause of morbidity and mortality in immunocompromised hosts. Congenital CMV infection occurs in approximately 0.5 to 1 percent of all newborns in the United States and can result in significant neurological sequelae. The gold standard for diagnosing congenital CMV infection is isolation of the virus from infants within the first 2 weeks of life through conventional or rapid cell culture techniques. Newer molecular diagnostic methods to diagnose congenital CMV infection, including the nucleic acid amplification of viral DNA from the peripheral blood of infants, are being investigated, and the preliminary results show promise. However, more work must be done to standardize and validate these methods before they can be used routinely in establishing the diagnosis of congenital CMV infection.     

Prevalence and clinical aspects of congenital cytomegalovirus infection

OBJECTIVES: The objectives of the present study were to determine the prevalence of congenital CMV infection, as well as to evaluate the importance of this agent as cause of congenital disease, and to describe the clinical manifestations in children attended at a General Hospital in Ribeir?o Preto, SP, Brazil. POPULATION AND METHODS: A first group including 189 newborns and their mothers was evaluated for the prevalence of the congenital CMV infection. A second group including 130 newborns and 74 infants who presented clinical manifestations of congenital disease were also investigated to evaluate the importance of the CMV as a cause of this disease and to describe the clinical findings. Diagnosis of congenital CMV infection was established by detecting the virus using viral isolation in tissue culture, polymerase chain reaction DNA amplification in urine samples and detection of specific anti-CMV IgM and IgG by immunofluorescence indirect test. RESULTS: The prevalence of congenital CMV infection was 2.6% and the prevalence of CMV antibodies in mothers was 95%. In the first group, none of the 5 congenitally infected presented clinical apparent disease at birth, although one of them had intracranial calcifications. In the second group, CMV was recognized as a causative of congenital disease in 12 children (5.9%). Of these, 10(83%) were identified after the neonatal period. The clinical findings included hepatosplenomegaly (75%), jaundice with direct hyperbilirubinemia (42%), neurologic disease consisting of microcephaly and intracranial calcifications in 42% of these children. CONCLUSIONS: The prevalence of congenital CMV infection was similar to that reported in other studies about highly immune populations. Infants with asymptomatic congenital CMV infection may have diseases of the central nervous system that are not clinically evident at birth, such as punctate calcifications. CMV infected patients who are symptomatic at birth have a multisystem disease, and the differential diagnosis of any newborn with clinical abnormalities including involvement of the hepatobiliary, hematopoietic and central nervous systems should include congenital CMV infection. CMV was an important agent of these abnormalities, and the majority of symptomatic patients were identified after the neonatal period, making the diagnosis more difficult.     

Congenital cytomegalovirus infection: association between virus burden in infancy and hearing loss

OBJECTIVE: To determine the relationship between the virus burden in infancy and hearing loss in congenital CMV infection. STUDY DESIGN: A cohort of 76 infants with congenital cytomegalovirus (CMV) infection identified by means of newborn virologic screening was monitored for outcome. The amount of infectious CMV was analyzed in urine specimens obtained during early infancy. Peripheral blood (PB) samples obtained during early infancy were available from 75 children and CMV DNA was quantitated with a real-time quantitative polymerase chain reaction. RESULTS: Infants with clinical abnormalities at birth (symptomatic congenital CMV infection) had higher amounts of CMV in urine (P = .005) and CMV DNA in PB (P = .001) than infants with no symptoms. Eight children with and 4 children without symptoms had hearing loss. Among children without symptoms, those with hearing loss had a significantly greater amount of CMV in urine (P = .03) and PB virus burden (P = .02) during infancy than those with normal hearing. Infants with < 5 x 10(3) pfu/mL of urine CMV and infants with < 1 x 10(4) copies/mL of viral DNA in PB were at a lower risk for hearing loss. CONCLUSION: In children with asymptomatic congenital CMV infection, hearing loss was associated with increased amounts of urine CMV and PB CMV DNA during early infancy.     

Antiviral therapy of congenital cytomegalovirus infection

Congenital infection caused by human cytomegalovirus (CMV) is a common occurrence, but its significance is underappreciated. In the developed world, congenital CMV infection confers a tremendous medical and economic burden on society. In recent years, appreciation of the scope of disability produced by such infections in newborns, which includes neurodevelopmental sequelae and sensorineural hearing loss (SNHL), has increased. Although much of the injury produced by infection in utero likely is irreversible, antiviral therapy of newborns with CMV infection is an option available to clinicians. Currently three antivirals are licensed for treatment of CMV: ganciclovir (and its prodrug, valganciclovir), foscarnet, and cidofovir. Novel antiviral therapies, which employ mechanisms of action that differ from these agents, also are in development. Experience with these agents in the setting of congenital and perinatal CMV infection is limited, but encouraging data come from a controlled clinical trial indicating that ganciclovir therapy may be of value in limiting the neurodevelopmental injury, particularly SNHL, caused by congenital infection. Newborn screening programs for CMV infection need to be developed and implemented. Infants with congenital CMV infection, once identified, could then be considered as candidates for antiviral therapy, and careful neurodevelopmental and hearing screening follow-up care plans could be established. CMV vaccines, once available, may ultimately be the best control strategy for this important public health problem.     

Multicity Italian study of congenital cytomegalovirus infection

BACKGROUND: Cytomegalovirus (CMV) infection is the most frequent congenital infection in humans. Its prevalence and the frequency of disabling sequelae must be assessed in different populations to permit the formulation or assessment of preventive measures. OBJECTIVES: To check the prevalence of congenital infection and seroprevalence in Italy; to verify the rate of sensorineural hearing loss (SNHL) in infected infants; and to assess the proportion of children with SNHL attributable to congenital CMV infection. METHODS: Diagnosis of congenital CMV infection was sought in 9032 children born between March 2002 and February 2003 by testing for viral DNA [CMV dried blood spot (DBS) test] in each newborn's Guthrie card and confirmation by isolation of CMV from urine collected in the first 3 weeks of life; CMV IgG testing in 1200 women of childbearing age; clinical and audiologic tests in the first 24 months for infected children; CMV DBS tests on the Guthrie cards collected from screening centers for 77 children (3 months-5 years) presenting SNHL of 40 dB or more. RESULTS: CMV infection was diagnosed in 14 asymptomatic and 2 symptomatic newborns (0.18%). CMV seroprevalence was 80%. In 2 infected infants, transient, unilateral SNHL was found. Nineteen of the 71 children with SNHL >70 dB were congenitally infected. CONCLUSIONS: The prevalence of congenital CMV infection is low in Italy. Population characteristics limiting the circulation of CMV strains in adult women might explain this. The fact that CMV contributes to significant SNHL highlights the need for preventive measures.     

CMV seroconversion in pregnants and the incidence of congenital CMV infection

In this study, it was aimed to determine the ratio of CMV seroconversion in pregnant women, the prevalence of maternal CMV infection and also the incidence of congenital CMV infection in their newborns in the Antalya region of Turkey. During a one-year period, CMV-specific IgG and IgM were determined in all (n: 1027) pregnant women admitted at 8 to 20 weeks of gestation, an according to the presence or absence of anti CMV-IgM and CMV-IgG, pregnant women were classified as seropositive, seronegative and having maternal CMV infection. Differentiation of primary and recurrent CMV infection in women with both CMV-IgM (+) and CMV-IgG (+) antibody was determined by the avidity index (AI) of anti-CMV IgG. Ultrasonographic examination was done and amniocentesis was performed at 21 to 23 weeks of gestation in pregnants with primary infection. CMV DNA was investigated in the amniotic fluid by quantitative polymerase chain reaction (qPCR). Pregnants with recurrent infection were followed only by ultrasonography for the presence of fetal abnormalities. Neonates born to mothers with CMV infection were examined for the findings of congenital CMV infection and screened for anti- CMV-IgM, CMV DNA and CMV antigenemia in the first two weeks of life. The rate of seropositivity was found as 98.5% and the rate of seronegativity as 1.5% in pregnant women. The prevalence of maternal CMV infection was found as 1.2% and among these pregnant women, the incidence of primary and recurrent maternal CMV infection was 0.3% (3 women) and 0.8% (12 women), respectively. Congenital CMV infection was detected in one of the newborns born to mothers with primary infection while no infection was detected in any of the newborns of mothers with recurrent CMV infection, so the incidence of congenital CMV infection was found as 0.1% and the rate of intrauterine infection following the primary maternal infection was 33%. In conclusion, seroprevalence rate of CMV in pregnants is high and most (66%) infections are recurrent maternal CMV infection in our region. Thus, it does not seem to be cost-effective to screen all pregnant women for CMV infection, as in the other countries with high seropositivity rate.     

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目的 探讨先天性巨细胞病毒(CMV)感染对患儿脑功能的影响及脑康复治疗的疗效.方法 以2004年1月至2007年11月在中南大学湘雅二医院新生儿科住院的81例先天性CMV感染患儿为研究对象,在用更昔洛韦治疗的同时,对其进行新生儿行为神经测试(NBNA)、头颅CT或MRI检测及听力检查.部分患儿在脑康复治疗后复查了NBNA测试.结果 81例患儿中,NBNA评分异常率为43.03%(34/79);29例患儿康复治疗后NBNA评分提高,差异有统计学意义.头颅影像学检查异常率为46.27%(31/67),影像学异常表现为脑实质灶性坏死或脑软化灶、脑发育迟缓、脑实质出血、脑室周围钙化及脑积水.听力筛查未通过率为50.68%(37/73),确诊听力障碍4例.结论 先天性CMV感染易导致脑损伤,对患儿早期进行脑功能监测并给予康复治疗有助于改善其预后.     

Congenital cytomegalovirus infection in preterm and full-term newborn infants from a population with a high seroprevalence rate

BACKGROUND: Cytomegalovirus (CMV) is the most frequent cause of congenital infections in humans. Prematurity occurs in as many as 34% of infants with symptomatic congenital CMV infection. OBJECTIVE: To determine the clinical presentation and frequency of congenital CMV infection among preterm infants and full-term infants from a population with a high seroprevalence rate. DESIGN/METHODS: A total of 289 preterm infants (median gestational age, 34 weeks; median birth weight, 1,757 g) and 163 term infants (median gestational age, 39 weeks; median birth weight, 3,150 g) sequentially born were included in the study. Serum IgG antibodies to CMV were measured in all mothers. One urine sample was collected within the first 7 days of age from all newborns. Virus isolation in urine samples was performed by tissue culture, and viral DNA was detected by a multiplex PCR. CMV infection was diagnosed in infants with virus excretion detected by both methods on at least two occasions within the first 3 weeks of life. RESULTS: Maternal CMV seropositivity rate was 95.7%. Congenital CMV infection was detected in 6 of 289 (2.1%) (95% confidence interval, 0.84 to 4.68) preterm infants and in 3 of 163 term infants (1.8%) (95% confidence interval, 0.48 to 5.74) (P > 0.05). Four of 6 preterm infants with congenital CMV infection were symptomatic, but none of the term infants was symptomatic (P = 0.16). CONCLUSION: The frequency of congenital CMV infection in preterm newborn infants from mothers with a high seropositive rate was similar to that found in term infants. No significant difference was found between the proportion of symptomatic infants among preterm and term infants. Our finding of symptomatic congenital CMV infection underscores the need of further evaluation of correlates of congenital symptomatic infection in highly immune populations.     

Sonography of subependymal cysts in congenital rubella syndrome

Two newborns with congenital rubella syndrome are reported. Cranial sonography demonstrated bilateral cystic lesions in the subependymal germinal matrix. Congenital rubella and cytomegalovirus (CMV) infections are the most common proven causes of subependymal cysts of nonhaemorrhagic origin in the newborn. The sonographic detection of these cysts should prompt an intensive search for congenital viral infectionsAbbreviations ABR auditory brainstem response - CMV cytomegalovirus - CT computed tomography - HAI Haemagglutination inhibition test - RV rubella virus - SEH subependymal haemorrhage     

Ophthalmological findings in congenital cytomegalovirus infection: when to screen, when to treat?

Cytomegalovirus (CMV) is the leading cause of known congenital viral infections. Approximately 90% of congenitally infected newborns exhibit no clinical abnormalities at birth. In 5% to 15%, a wide spectrum of clinical signs is present at birth. Ophthalmological signs are seen in a large percentage of symptomatic patients but rarely in otherwise asymptomatic infants. Chorioretinitis, optic atrophy, and cortical visual impairment are the most frequent causes of visual problems in congenitally infected infants. There is no clear consensus in the literature on screening or treatment modalities concerning the ophthalmological aspects of congenital CMV. Further prospective studies are needed to set up guidelines for ophthalmological screening and treatment of infants with congenital CMV.     

Neuroimaging in CMV congenital infected neonates: how and when

Neonatal congenital infections are an important cause of mortality, morbidity and long-term neurodevelopmental and sensorineural sequelae. Many pathogens can cause in utero infection, and among them, cytomegalovirus (CMV) plays a prominent role. In developed countries, CMV poses major health problems as it is the most common pathogen leading to congenital infection, and the leading cause of nonhereditary deafness in children. Evaluation of central nervous system (CNS) involvement in congenital CMV infected newborns is mandatory to better assess the severity of the disease, to guide adequate treatment, to define prognosis, and to tailor follow-up observations and parents' counselling. Cerebral ultrasonography (cUS), Computed Tomography (CT), and Magnetic Resonance Imaging (MRI) are the currently available techniques to evaluate infants with suspected or proven congenital CMV infection. In congenital CMV infection, their role in early detection and confirmation of cerebral involvement within the first month of life is crucial to initiate specific treatment with antivirals. Neonatologists, paediatricians and radiologists should be aware of the role, the limitations and the inherent risks related to the use of these specific neuroimaging diagnostic tools in these infants. In this article we will discuss from a neonatological perspective the advantages, disadvantages, risks and limitations of each imaging technique.     

Prenatal indicators of congenital cytomegalovirus infection

OBJECTIVE: To assess the validity of a diagnostic protocol designed to predict the outcome of newborns of mothers suspected to have primary cytomegalovirus (CMV) infection during the first 4 months of pregnancy. STUDY DESIGN: Anti-CMV immunoglobulin (Ig) M detection by enzyme immunoassay and immunoblot together with the determination of anti-CMV IgG avidity allowed us to classify 456 women as (1) uninfected, (2) undergoing either a primary or a recurrent infection, or (3) having an undefined serologic condition. Prenatal diagnosis was carried out at 21 to 23 weeks' gestation for women. The presence of the virus in the amniotic fluid was determined by culture, polymerase chain reaction, and quantitative polymerase chain reaction. Macroscopic and histologic examinations were undertaken on tissue from aborted fetuses, whereas for newborns culture was performed on urine sampled during the first week of life. RESULTS: Congenital infections were found exclusively among women undergoing a primary infection. The quantitative determination of CMV DNA in the amniotic fluid of at least 10(3) genome equivalents gave a 100% certainty of detecting an infected fetus. Higher viral loads were associated with fetuses or newborns with symptoms. CONCLUSIONS: IgM tests and the IgG avidity determination can identify all women at risk of transmitting CMV. Furthermore, a high CMV DNA load in amniotic fluid could be an indicator of symptomatic congenital infection at a relatively early stage of pregnancy.     

婴幼儿巨细胞病毒感染的临床特点及转归

目的研究巨细胞病毒(CMV)感染住院婴幼儿的临床发病特点及疾病转归。方法对符合CMV感染的87例婴幼儿从感染CMV后的发病时间,CMV侵袭器官所致器官相应损害的临床发病类型,实验室及相关影像学检查包括头颅B超,胸部X线及脑干视、听觉诱发电位检查及疾病转归进行综合分析。结果87例CMV感染婴幼儿中先天性CMV感染占27.6%,围生期CMV感染占62.0%,生后CMV感染占16.6%;CMV肝炎是最常见的临床类型,发生率为41.3%,其中脾大发生率10.3%,多数患儿预后好,好转率80.5%;中枢神经系统异常的发生仅见于先天性和围生期感染患儿,本组神经系统异常发生率20.4%;先天性CMV感染中全身性感染占16.7%,围生期全身性感染占1.8%,生后感染者无全身性感染发生;先天性CMV感染的死亡率12.5%,围生期感染的死亡率1.85%。结论CMV感染是导致婴幼儿肝炎综合征的重要原因,是造成婴幼儿神经系统后遗症不可忽视的因素;先天性CMV感染中全身性感染病死率高,预后差。     

Detection of congenital cytomegalovirus infection in Chinese newborn infants using polymerase chain reaction

Polymerase chain reaction (PCR) amplification was used to detect cytomegalovirus (CMV) in 1000 urine specimens from Chinese newborns for defining the incidence of congenital CMV infection in the Chinese population. The major immediate-early and the late antigen genes of CMV were amplified and detected by gel electrophoresis. There were 18 congenitally infected infants found when tests were performed with one or both primer pairs. Comparing with tissue culture, PCR of both primer sets provided a sensitivity of 94%, a specificity of 100% and a predictive value of positive result of 100%.     

上海市三级和一级医院新生儿先天性巨细胞病毒感染横断面调查

目的 通过上海市区的三级甲等医院和相对远离上海市区的一级医院先天性巨细胞病毒（CMV）检测,反映上海地区先天性CMV感染情况。方法 收集复旦大学附属妇产科医院（简称复旦妇产医院）和上海闵行区浦江镇社区卫生服务中心（简称浦江医院）出生时活产的、并行新生儿疾病筛查的新生儿,利用新生儿疾病筛查后余下的干血斑点（DBS）标本以荧光定量PCR方法检测CMV DNA载量,根据新生儿疾病筛查信息和电话随访分析先天性CMV感染危险因素。危险因素定义如下：性别;出生胎龄（胎龄＜37周、～42周和≥42周）;出生体重（＜2 500 g、～3 999 g和≥4 000 g）;母亲分娩年龄（25~30岁、>30岁第1胎或≥35岁）;户籍（上海和非上海市户籍）;教育程度（初中及以下、高中、大学及以上）;家庭人口数（≤3口人、4口人、>5口人）。结果 2011年9月至2013年3月1 780份DBS标本用于CMV感染率的分析,其中浦江医院942份,复旦妇产医院838份,两医院先天性CMV总感染率为0.9%（17/1 780）,其中浦江医院感染率为1.6%（15/942）,复旦妇产医院感染率为0.2%（2/838）,差异有统计学意义（P=0.003 4）。共收集到1 530例新生儿及母亲临床资料的电话随访数据,CMV阳性和阴性新生儿母亲文化程度差异有统计学意义(P=0.008 5),其他危险因素两组间差异均无统计学意义。结论 上海地区先天性CMV感染率为0.9%,与性别、胎龄、出生体重及母亲户籍、家庭人口数不相关,与母亲教育程度相关。     

Predicting the outcome of symptomatic congenital cytomegalovirus infection

Abstract The prognosis of babies with symptomatic congenital cytomegalovirus (CMV) infection is worse than for those with asymptomatic CMV, but is difficult to quantify. Babies affected as a result of primary maternal CMV are at greater risk than after reactivation CMV. Chorioretinitis occurs in 10–15% of symptomatic babies and almost always indicates significant mental impairment. Microcephaly occurs in around 50% at birth, but does not always persist, and does not necessarily imply later neurological handicap. Investigative findings that increase the likelihood of handicap include radiographic or computerized tomography scan finding of intracranial calcification and raised cerebrospinal fluid protein. Late deafness is always unpredictable and all babies with congenital CMV infection should have an audiological follow up. The mortality of symptomatic congenital CMV infection is about 30%.