Neonatal Cytomegalovirus Blood Load and Risk of Sequelae in Symptomatic and Asymptomatic Congenitally Infected Newborns (original) (raw)
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CMV is a ubiquitous virus. In India, there is high seroendemicity with almost 99% adults showing IgG antibodies. Infection or re-activation becomes important in immunocompromised host (Transplant recipients, Cancer therapy patients and patients with HIV/AIDS). Neonates form a distinctive high risk population for congenital CMV infection and suffer disastrous sequlae of the same. Neonatal infections may be congenital in nature or may be acquired after birth during first month of life via infected breast milk or due to exposure to high risk blood products. The risk for transmission of the virus to the fetus is higher in primary infected mothers than in mothers with reactivated disease. Primary CMV infections are reported in 1-4% of seronegative women during pregnancy and the risk for viral transmission to fetus is 30-40%. Reactivation of a CMV infection during pregnancy is reported in 10-30% of seropositive women and the risk of transmitting the virus is about 1-3%. The adverse outcome of congenital neonatal CMV infection includes-microcephaly (70%), intellectual impairment (60%), sensineural hearing loss (35%), choriorenitis (22%), hepatosplenomegaly (70%), jaundice (68%), thrombocytopenia (65%), low birth weight (65%), pneumonitis (2-5%) and congenital heart disease (<5%). About 5-10% of congenitally infected asymptomatic infants will have neurological problems later in life the most common of which is unilateral or bilateral sensory neural hearing loss. All immunocompromised hosts, including pre-term neonates, mount weak antibody responses (IgM), making serological detection of CMV infection in them, fallacious. Thus, it is imperative to use antigen detection methods such as quantitative PCR or PP65 Antigenaemia assays to detect CMV infection in immunocompromised host. Sakhuja et al and Minz et al have demonstrated that PP65 Antigenaemia assay is very good for diagnosing CMV disease in renal transplant recipients. The present review tends to highlight the role of newer diagnostic modalities in early CMV infection detection in neonatal population. [Indian J Pediatr 2010; 77 (1) : 77-79]
Neonatal cytomegalovirus infection: Diagnostic modalities available for early disease detection
The Indian Journal of Pediatrics, 2009
CMV is a ubiquitous virus. In India, there is high seroendemicity with almost 99% adults showing IgG antibodies. Infection or re-activation becomes important in immunocompromised host (Transplant recipients, Cancer therapy patients and patients with HIV/AIDS). Neonates form a distinctive high risk population for congenital CMV infection and suffer disastrous sequlae of the same. Neonatal infections may be congenital in nature or may be acquired after birth during first month of life via infected breast milk or due to exposure to high risk blood products. The risk for transmission of the virus to the fetus is higher in primary infected mothers than in mothers with reactivated disease. Primary CMV infections are reported in 1-4% of seronegative women during pregnancy and the risk for viral transmission to fetus is 30-40%. Reactivation of a CMV infection during pregnancy is reported in 10-30% of seropositive women and the risk of transmitting the virus is about 1-3%. The adverse outcome of congenital neonatal CMV infection includes-microcephaly (70%), intellectual impairment (60%), sensineural hearing loss (35%), choriorenitis (22%), hepatosplenomegaly (70%), jaundice (68%), thrombocytopenia (65%), low birth weight (65%), pneumonitis (2-5%) and congenital heart disease (<5%). About 5-10% of congenitally infected asymptomatic infants will have neurological problems later in life the most common of which is unilateral or bilateral sensory neural hearing loss. All immunocompromised hosts, including pre-term neonates, mount weak antibody responses (IgM), making serological detection of CMV infection in them, fallacious. Thus, it is imperative to use antigen detection methods such as quantitative PCR or PP65 Antigenaemia assays to detect CMV infection in immunocompromised host. Sakhuja et al and Minz et al have demonstrated that PP65 Antigenaemia assay is very good for diagnosing CMV disease in renal transplant recipients. The present review tends to highlight the role of newer diagnostic modalities in early CMV infection detection in neonatal population. [Indian J Pediatr 2010; 77 (1) : 77-79]
Prenatal indicators of congenital cytomegalovirus infection
The Journal of Pediatrics, 2000
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.
Indian Journal of Medical Microbiology, 2015
in the general population is between 50-70%, [3,4] the corresponding fi gure for the developing nations ranging from 70-100%. In India, this fi gure approaches 98-100%. [5] The rates of congenital infection in developed countries are about 0.6-0.7% of live births, whereas in the developing world, higher rates between 1-5% have been observed. [1,3] Congenital HCMV infection is asymptomatic in more than 90% of infected infants, whereas the remaining 10% show manifestations including microcephaly, small for gestational age (SGA), neonatal hepatitis, hepatomegaly, splenomegaly, chorioretinitis, cataract, thrombocytopenia, etc, Some of these symptomatic infants also develop sensorineural hearing loss (SNHL) in the ensuing few years. [2] A fraction of infants who were asymptomatic at birth also go on to develop complications like SNHL and neurodevelopmental delays in the next few years of their lives. In fact, it is now established that congenital HCMV infection is the leading cause of nonsyndromic SNHL in the developed world. [2] The diagnosis of congenital HCMV infection has traditionally been based on demonstration of the virus in urine by isolation in cell culture. Owing to the slow turnaround time for cell culture and its low sensitivity, demonstration of HCMV DNA in urine by PCR has gradually replaced virus isolation. [2] Demonstration of IgM antibodies to HCMV (anti-HCMV IgM) is a common diagnostic test in neonates or infants, which suggests current infection and supports the diagnosis. Other tests, utilising
New advances in the diagnosis of congenital cytomegalovirus infection
Journal of Clinical Virology, 2008
Although the diagnosis of congenital CMV infection is still complex, important goals have been achieved in recent years, among which are: the availability of more reliable IgM tests for screening pregnant women whose pre-pregnancy serological status for CMV is unknown, tests to determine the avidity index of anti-CMV IgG, allowing the diagnosis of a primary CMV infection and innovative and traditional virological tests to detect the virus in amniotic fluid. When a woman is found to be IgM-positive, further diagnostic evaluation focused on determining whether this is due to a primary infection should be carried out. Maternal primary infections that were difficult to determine until a few years ago unless documented by seroconversions can now be readily diagnosed from the presence of low/moderate avidity anti-CMV antibody which persists for approximately 18-20 weeks after primary infection. In mothers at risk of transmitting the virus prenatal diagnosis can be performed between 21 and 22 weeks of gestation, and the amniotic fluid represents the pathological material of choice to determine intrauterine virus transmission. At birth or in the first 2/3 weeks of life, it is essential to use appropriate tests for diagnosis of CMV congenital infection.
International Journal of Molecular Sciences, 2021
Congenital cytomegalovirus (CMV) infection may cause severe long-term sequelae. Recent studies have demonstrated that early antiviral therapy for infants with symptomatic congenital CMV (cCMV) infection may improve neurological outcomes; thus, accurate identification of newborns at high risk of cCMV infection may contribute to improved outcomes in affected children. However, maternal serological screening for cCMV infection by diagnosing primary infection during pregnancy, which is a popular screening strategy, is inefficient, because the number of cCMV infections with nonprimary causes, including reactivation of or reinfection with CMV, is larger than that of cCMV infections with primary causes. Low levels of neutralizing antibodies against pentameric complex and potent CMV-specific T cell-mediated immune responses are associated with an increased risk of cCMV infection. Conversely, our prospective cohort studies revealed that the presence of maternal fever/flu-like symptoms, threa...
BMC infectious diseases, 2017
Cytomegalovirus (CMV) is a common cause of congenital infection worldwide and infants with symptomatic congenital CMV (cCMV) infection are at significantly increased risk of developing adverse long-term outcomes. This study aimed to determine the prevalence of cCMV infections in symptomatic infants under 3 weeks in Tehran, IRAN and to evaluate the usefulness of serologic markers in these neonates. Urine and serum samples of 100 symptomatic infants, under 3 weeks old, with clinical signs referred to Tehran medical centers from June 2013 to December 2014, were collected and tested for CMV-DNA and IgG/IgM antibody titers by PCR and ELISA, respectively. CMV-DNA was detected in urine of 58 cases, whereas only 20 cases had detectable CMV-IgM titers. All CMV-IgM positive cases excreted CMV-DNA through their urine. Of the 100 patients, only 59 had CMV-IgG antibody and CMV-DNA was found in the urine of only 40 of them. We conclude that CMV is an important etiologic agent of congenital infect...
The Journal of infectious diseases, 2014
We investigated the kinetics of cytomegalovirus (CMV) clearance in blood and urine and the relationship between the viral load in blood at birth and the development of late-onset sequelae in asymptomatic congenital CMV infection. Thirty-three newborns with congenital asymptomatic CMV infection born to women with primary CMV infection during pregnancy were enrolled. CMV infection was monitored by polymerase chain reaction analysis of blood and urine. The follow-up examination was concluded at 6 years of age. Ten infants developed postnatal sequelae, whereas twenty-three infants remained asymptomatic. Fifty percent of babies cleared CMV in blood and urine within 3 and 36 months, respectively. Logistic multivariate regression revealed that the risk of neonatal clinical disease crossed the level of 50% with a DNAemia at birth of ≥12 000 copies/mL (P = .0002). The risk of hearing deficit crossed the level of 50% with a DNAemia at birth of ≥ 17 000 copies/mL (P = .0001). No significant...
Pediatric Infectious Disease Journal, 2020
Background: Cytomegalovirus (CMV) is the leading cause of congenital infection worldwide. Up to 15%–20% of infected newborns will develop long-term sequelae such as hearing loss and neurologic abnormalities. The aim of this study was to investigate the prevalence of congenital CMV infection (cCMV) and associated clinical abnormalities in Spain. Methods: A prospective screening for cCMV by viral load in saliva was performed. Saliva samples were obtained within the first 72 hours of life in a maternity ward in Madrid (Spain), during a 1-year period. All positive screening tests were confirmed with viral load in urine. Clinical, laboratory, auditory, visual and cerebral imaging assessments were performed in all children with cCMV. Results: Of the 4097 neonates born during the study period, 3190 (78%) were included. CMV viral load in saliva was detectable in 24/3190 (0.75%) children, and congenital infection was confirmed in 15/3190 (0.47%, CI 95%: 0.29%–0.77%). Positive predictive valu...
Evaluation of clinically asymptomatic high risk infants with congenital cytomegalovirus infection
Journal of Perinatology
Objective To determine the frequency of abnormal findings on evaluation of neonates with congenital CMV infection who have a normal physical examination Study design Retrospective, 2-center study (1996-2017) that reviewed results of complete blood cell count and platelets, serum alanine aminotransferase (ALT) and bilirubin concentrations, eye examination, cranial ultrasonography or other neuroimaging, and brainstem evoked responses performed on neonates with congenital CMV infection and a normal physical examination Results Of 34 infants with congenital CMV infection and a normal physical examination, 56% (19/34) had ≥1 abnormality: 39%, elevated ALT concentration; 45%, abnormal neuroimaging (five, lenticulostriate vasculopathy; six, intraventricular hemorrhage; four, calcifications); 12%, anemia; 16%, thrombocytopenia; and 3%, chorioretinitis. Seven (21%) infants had sensorineural hearing loss, and 18 infants received antiviral therapy. Conclusion Some infants with congenital CMV infection and a normal physical examination had abnormalities on laboratory or neuroimaging evaluation, which in some cases prompted antiviral treatment.