Congenital cytomegalovirus (CMV) is the commonest cause of congenital infection worldwide and the leading non-genetic cause of sensorineural hearing loss in children. Appropriate investigations and timely decision on treatment is required as studies have shown that treatment with antiviral therapy leads to improved hearing and neurodevelopmental outcomes in the long term when started in the first month of life. This paper outlines the epidemiology, investigations in the diagnosis of congenital CMV infection and current evidence surrounding treatment.
2024, American Journal of Obstetrics and Gynecology
Recent studies have shown that a dosage of 8 g/d of oral valacyclovir reduces substantially the vertical transmission rate of cytomegalovirus in women with primary cytomegalovirus infection acquired periconceptionally or during the first trimester of pregnancy. This individual patient data meta-analysis aimed to assess the effectiveness and safety of valacyclovir treatment in the secondary prevention of congenital cytomegalovirus infection.
MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, the US registry of clinical trials (www.clinicaltrials.gov), and gray literature sources were searched from inception to March 2023.
Randomized controlled trials and quasi-randomized studies administering 8 g/d of oral valacyclovir in pregnant women with primary cytomegalovirus infection acquired periconceptionally or during the first trimester of pregnancy were included.
All corresponding authors of the eligible studies were contacted. Cochrane’s Risk of Bias 2 and Risk Of Bias In Non-randomised Studies - of Interventions tools were used for the risk of bias assessment. The result of amniocentesis was the primary outcome of interest. A 1-stage individual patient data meta-analysis was performed, using a generalized linear mixed model, clustered by the different trials. A subgroup analysis was performed, assessing separately the effect of valacyclovir in the periconceptional period and first trimester of pregnancy.
Overall, 3 studies were included in the analysis (n=527 women). Valacyclovir reduced the vertical transmission rate of cytomegalovirus (adjusted odds ratio, 0.34; 95% confidence interval, 0.18–0.61). This reduction was apparent for both periconceptional period (adjusted odds ratio, 0.34; 95% confidence interval, 0.12–0.96) and first-trimester (adjusted odds ratio, 0.35; 95% confidence interval, 0.16–0.76) infections. Moreover, valacyclovir reduced the rate of neonatal infection (adjusted odds ratio, 0.30; 95% confidence interval, 0.19–0.47), in both periconceptional period (adjusted odds ratio, 0.30; 95% confidence interval, 0.14–0.61) and first-trimester (adjusted odds ratio, 0.30; 95% confidence interval, 0.17–0.54) infections. Furthermore, valacyclovir reduced the rate of termination of pregnancy because of cytomegalovirus-associated severe fetal findings (adjusted odds ratio, 0.23; 95% confidence interval, 0.22–0.24). The gestational age at the initiation of treatment has a positive correlation with all outcomes. The overall prevalence of severe side effects was 2.1%.
A dosage of 8 g/d of oral valacyclovir reduced the vertical transmission rates of cytomegalovirus following primary maternal infection acquired periconceptionally or in the first trimester of pregnancy, with a low incidence of side effects.
The interplay of active HCMV infection with gut dysbiosis in the immunopathology of cholestasis in neonates and infants remains unexplored. In this study, we evaluated gut microbiome profiles and immune dysfunction in a cohort of HCMV infected cholestatic infants (IgM positive, N = 21; IgM negative, N = 25) compared to healthy infants, N = 10. HCMV infected IgM positive individuals exhibited increased clinical severity in terms of liver dysfunction, altered CD4+: CD8+ ratio, and elevated Granzyme B levels in cellular immune subsets. Gut microbiome analysis revealed distinct and differential diversity and composition within infected groups aligned with clinical severity reflected through the increased abundance of Gammaproteobacteria, reduced Bifidobacteria, and a unique signature mapping to the HCMV infected IgM negative group. Correlation analyses revealed associations between Bifidobacterium breve, Gammaproteobacteria, Firmicutes, Clostridia, Finegoldia magna, Veillonella dispar, and Granzyme B expressing immune cell subsets. Our study describes a novel gut microbiome–immune axis that may influence disease severity in cholestatic infants with active HCMV infection.
To describe the evolution of the intracranial features of congenital cytomegalovirus (cCMV) on magnetic resonance imaging (MRI).
Sixteen infants with polymerase chain reaction (PCR)-confirmed cCMV who had undergone at least two MRI examinations of the brain were identified. Two paediatric neuroradiologists reviewed the baseline studies retrospectively for intracranial features of cCMV, including white matter signal abnormalities, subependymal cysts, malformations of cortical development, and intracranial calcification. The subsequent MRI studies were then reviewed and directly compared to the baseline examinations.
White matter signal abnormalities were seen on all 16 baseline studies (100%); these persisted on all subsequent examinations but were patchier, more focal, and associated with an interval reduction in white matter volume. Subependymal cysts were present on 11 (69%) of the baseline scans; these almost universally regressed (in 10 of the 11 cases [91%]), with no new cysts appreciable on subsequent imaging. Malformations of cortical development, exclusively in the form of polymicrogyria, were seen in six (38%) patients and persisted, unchanged, on subsequent imaging. Intracranial calcification was seen in a minority of baseline studies (4 [25%]) and remained stable on subsequent scans.
Children with cCMV who present later in life without an established or suspected underlying pathology can pose a challenge to the assessing radiologist. The radiological sequelae of cCMV can be non-specific; in some cases, white matter signal abnormalities and focal loss of white matter volume may be the only intracranial features. It is therefore important that radiologists are aware of cCMV as a potential differential for these findings.
Viral infections of the fetus and newborn are common and frequently under recognized. Viral infections can be acquired in utero, intrapartum, or postpartum. The outcome of infection frequently depends on the timing of acquisition. The consequences of some infections can be evident at birth when infants present with symptoms such as intrauterine growth restriction, hepatitis, thrombocytopenia, and neurologic abnormalities. In other infections, the infant may be asymptomatic at birth but develop severe disease in the neonatal period. Timely and specific identification of viral infections is important as there are an increasing number of antiviral therapeutic agents available and appropriate treatment can be lifesaving. Identification of viral disease in the neonate may also provide important prognostic information, particularly for viruses associated with a high risk of neurodevelopmental issues. Accordingly, making a diagnosis of a viral infection can help to direct and focus long-term management. Fortunately, with the availability of molecular tools for specific viral detection using polymerase chain reaction (PCR) amplification of viral nucleic acid, virtually all pathogenic viruses can be rapidly identified. This chapter reviews the epidemiology, pathogenesis, diagnosis, clinical management, outcomes, and prevention of many common congenital and perinatal viral infections encountered in neonates.
2022, Journal of Microbiology, Immunology and Infection
Citation Excerpt :
Till date, a number of studies on CMV vaccine development have been performed in clinical settings, without any promising results.16 Unlike well-assessed epidemiologic features including the transmission rate to the fetus in congenital CMV infection, the global incidence trend for CMV end-organ diseases in the general population encompassing severely immunocompromised and immunocompetent individuals has not been fully evaluated.12,17 Several studies analyzing anti-CMV-immunoglobulin G tests have shown that CMV seroprevalence rates varied from 20 to 100% according to region, race, socioeconomic status, sex, and age.9,18
Cytomegalovirus (CMV) can cause tissue-invasive diseases in various organs after primary infection or through reactivation of latent-to-lytic switch over a lifetime. The number of individuals who are at risk of CMV diseases, such as elderly or immunocompromised patients, is constantly increasing; however, recent epidemiological changes associated with CMV disease have not been fully evaluated.
We used claims data of about 50 million individuals between 2010 and 2015 from the Korean Health Insurance Review and Assessment Service nationwide database. The code for CMV end-organ diseases in the ‘Relieved Co-payment Policy’ program matches the ICD-10 code of B25, except for congenital CMV infection and mononucleosis. A 628 cases of CMV and 3140 controls (without CMV disease), matched for age and sex, were selected from this dataset in order to evaluate the effect of adult CMV diseases on all-cause death.
The overall unadjusted incidence rate (IR) of CMV end-organ diseases was 0.52/100,000 individuals. The standardized IR, adjusted for age and sex, have continuously increased from 0.32/100,000 in 2010 to 0.75/100,000 in 2015. The overall unadjusted IR in adult population was highest in 70–79 years for six years (0.96/100,000). In the model adjusted for age, sex, immunocompromised status including solid-organ or hematopoietic stem cell transplant recipients, hematologic malignancies, and human immunodeficiency virus diseases, the hazard ratio of case group was 5.2 (95% confidence interval, 3.6–7.4) for all-cause mortality.
Nationwide data indicates that CMV end-organ disease has steadily increased in the past six years and is associated with higher mortality.