Search Results (133)

Congenital cytomegalovirus infection is an underrecognized congenital infection. Globally, it impacts approximately 1 of every 200 live births. Although infected infants can have an increased risk of long-term sequelae, such as neurodevelopmental impairments and sensorineural hearing loss, most of the infected infants do not show visible signs at birth. As congenital cytomegalovirus infection often goes undetected and screening programs are not widely accepted, awareness of congenital cytomegalovirus in neonates is lacking. The aim of this study is to offer the current status of the epidemiology, clinical manifestations, and laboratory testing for the diagnosis of congenital cytomegalovirus infection and newborn screening approaches. Full article

Parvovirus B19 and cytomegalovirus are significant causes of congenital infections that can lead to adverse pregnancy outcomes. The present study aimed to investigate the infection of B19V and CMV in pregnant women with fetal anemia, effusions and intrauterine growth restriction and determine the utility of routine laboratory screening in pregnancy follow-up. Thirteen women with such pathological pregnancy complications attending an antenatal clinic from April 2024 to March 2025 were tested. Three types of clinical material were examined: maternal blood, amniotic fluid and umbilical cord serum. Participants underwent molecular and serological testing for both B19V and CMV. Demographic data, obstetric histories, and pregnancy outcomes were recorded and analyzed. Our results indicate that three participants showed evidence of either current infection with CMV and seven with B19V. Pregnant women with active infections required further follow-up and fetal surveillance. A stillbirth was reported in one woman with CMV infection. For seven samples that tested positive for B19V DNA, viral sequences were obtained and clustered with genotype 1a reference strains. The findings of this study highlight the significant contribution of B19V and CMV infections during pregnancy, particularly in cases complicated by fetal anemia, effusions, and intrauterine growth restriction. Full article

Cytomegalovirus (CMV) is the most common infectious cause of congenital malformations, often presenting with atypical clinical findings. Fetal damage is most severe following primary maternal infection during the first trimester of pregnancy, with the likelihood of transmission increasing with pregnancy advancement. CMV damage may continue to intensify during the early postnatal years. In this narrative review we summarized publications from the last 30 years addressing the epidemiology, diagnosis, prevention and treatment of CMV in pregnancy, with a special emphasis on embryonic and fetal damage. Substantial progress has been made in the diagnosis and treatment of CMV infection during pregnancy, warranting a reconsideration of current clinical approaches. Assessment of viral load enables prediction of fetal infection; its reduction by maternal treatment with valacyclovir may lower both the rate and severity of transmission. Confirmed fetal infection can be diagnosed by amniocentesis and viral DNA detection. Clinical manifestations in infants may be evident at birth (cCMV) or gradually emerge during the first years. The most common fetal damage is hearing loss alongside a variety of brain lesions resulting in significant neurological deficits, including intellectual impairment. Brain involvement is diagnosed by ultrasound or magnetic resonance imaging (MRI). Pharmacological treatment with ganciclovir or valganciclovir, if initiated early after birth, can slow the progression of hearing loss and may ameliorate other neurological and neurodevelopmental deficits. As of today, there is no approved CMV vaccine for prevention. The mRNA-1647’s vaccine, currently in phase 3 clinical trial, appears promising. These advances underscore the need for screening pregnant women in the first trimester and newborn infants of mothers suspected of having CMV infection. Neurodevelopmental follow up for several years, including hearing and visual assessment, is advised in all infants positive for CMV. Infants with clinical manifestations should be offered treatment as early as possible following diagnosis of cCMV. Full article

Background/Objectives: Cytomegalovirus (CMV)-associated hearing loss is common in non-genetic congenital hearing loss. Despite this high prevalence, a wide range of clinical characteristics exists, and the pattern of hearing loss remains unknown. This study aims to describe the clinical manifestations in children with CMV-associated hearing loss and to clarify the timing of hearing level change and the degree of hearing level fluctuation. Methods: A total of 54 patients with hearing loss due to congenital CMV infection were included. Hearing loss type (congenital or later onset), hearing loss laterality (unilateral or bilateral), severity at first and last visit, hearing progression and timing, and the difference between patients with intellectual disability and without intellectual disability were assessed. Results: The number of patients with congenital hearing loss and later onset hearing loss were 19 patients and 13 patients, respectively. Seventy-four percent (14/19) of the congenital hearing loss patients and 62% (8/13) of the later onset hearing loss patients eventually progressed to severe to profound hearing loss bilaterally. Progression occurred in less than 1 year (9 cases), between 1 and 3 years (7 cases), between 3 and 7 years (4 cases), or more than 8 years (1 case). Multiple progression events occurred in 11 cases. Conclusions: Sixty-one percent of patients had progression of hearing loss. Several cases experienced progression over more than one year and showed multiple progression events. CMV patients without intellectual disability tended to suffer later onset hearing loss. Sixty-nine percent of the patients eventually progressed to bilateral severe to profound hearing loss, which means that continuous long-term follow-up is required. Full article

Congenital cytomegalovirus infection (cCMV) is one of the most common congenital infections. This study aimed to evaluate the diagnostic performance of targeted screening with the use of clinical risk factors for cCMV. A total of 3063 pregnant women and their 3139 newborns were enrolled. Six clinical findings consisting of maternal fever or flu-like symptoms during pregnancy (fever/flu-like symptoms), hospitalization for threatened miscarriage or preterm labor before 34 weeks of gestation, preterm delivery before 34 weeks of gestation, fetal ultrasound abnormalities, small for gestational age (SGA), and refer results of automated auditory brainstem response screening (AABR refer) were defined as cCMV risk factors before participant registration. All newborns underwent urine cytomegalovirus polymerase chain reaction tests within one week of birth. The predictive accuracy of these six risk factors was analyzed. Nine (0.29%) of the three thousand one hundred and thirty-nine newborns were diagnosed with cCMV, having at least one of the six risk factors. Logistic regression analysis identified fever/flu-like symptoms (odds ratio (OR), 7.5; 95% CI, 1.9–30.3), fetal ultrasound abnormalities (OR, 17.9; 95% CI, 4.4–72.8), SGA (OR, 6.8; 95% CI, 1.8–25.6), and AABR refer (OR, 75.5; 95% CI, 19.7–289) as significant risk factors. The predictive accuracy of the targeted screening for cCMV, when at least one of the six risk factors was present, yielded 100% sensitivity (95% CI, 55.5–100) and 70.7% specificity (95% CI, 69.1–72.3), with a Youden index of 0.707. When at least one of the four significant risk factors was present, 100% sensitivity (95% CI, 55.5–100) and 81.2% specificity (95% CI, 79.8–82.6) with the maximum Youden index of 0.812 were achieved. In conclusion, targeted screening with the use of clinical risk factors in mothers and their newborns could effectively identify cCMV. Full article

Due to possible congenital infections, cytomegalovirus (CMV) remains a significant public health concern in childbearing-aged and pregnant women. We analyzed the spatial, temporal, and age-related trends in CMV seroepidemiology in Croatia over 10 years. A total of 2838 childbearing-aged and pregnant women, aged 16–45 years, tested between 2015 and 2024 were included in the study. CMV IgM/IgG antibodies were detected using a commercial ELISA. IgM/IgG-positive samples were tested for IgG avidity. CMV IgG antibodies were detected in 2006 (70.6%) of participants. No significant differences were observed between 2015–2019 and 2020–2024 (72.0% vs. 69.8%), while yearly differences were of borderline significance, ranging from 62.4 to 77.3%. The overall seropositivity increased progressively with age from 49.6% in the 16–20 age group to 77.5% in the 36–40 age group. Significant regional differences in IgG seroprevalence were observed: 68.6% in the City of Zagreb/Northern Croatia, 78.5% in Pannonian Croatia, and 71.9% in Adriatic Croatia, while differences between settlement types were not significant. IgG seroprevalence was higher in women with an unfavorable obstetric history (85.3%) than in non-pregnant women and those with a normal pregnancy (70.6% and 66.5%, respectively). IgM antibodies were detected in 278 (9.8%) of participants. Acute infections were more common in younger participants, with rates decreasing from 13.6% in the youngest age group to 6.7% in the oldest. Logistic regression showed that age was a significant predictor of both IgG and IgM positivity. Region and obstetric history were significant predictors of IgG seropositivity, while settlement was a significant predictor of IgM seropositivity. Full article

Human cytomegalovirus (HCMV) is the leading viral cause of congenital infections and causes substantial morbidity and mortality in neonates and immunosuppressed people. Generating an anti-HCMV vaccine is required for preventing viral-associated diseases and infections. Oral vaccines based on attenuated Salmonella are an attractive solution, since these vaccines can be applied orally and easily for mass immunization. In this report, we constructed an attenuated Salmonella strain for the expression of the murine cytomegalovirus (MCMV) M43 protein and studied its ability as an oral vaccine candidate to stimulate antiviral immunity in mice. In orally immunized mice, the constructed vaccine, Sal-M43, elicited both serum IgG and mucosal IgA levels as well as T cell responses that were specific against the MCMV M43 protein. Moreover, the Sal-M43 immunization substantially inhibited the viral growth and infection in various organs and tissues and offered complete immune protection against both intraperitoneal and intranasal MCMV challenges. Thus, the Salmonella-based vaccine expressing the M43 antigen is effective in inducing anti-MCMV immunity. These findings also reveal the promise of developing oral anti-CMV vaccines based on attenuated Salmonella vectors expressing different viral antigens. Full article

Cytomegalovirus (CMV) is the leading infectious cause of birth defects and has been linked to increased risk of preterm birth (PTB). CMV establishes lifelong latency and is more prevalent among Black and Hispanic/Latina women, populations already at higher risk for adverse pregnancy outcomes. Vitamin D deficiency, also common in these groups, has been linked to impaired immune function and increased susceptibility to infections, including CMV. In this cross–sectional study of 63 pregnant minority women (50 CMV+, 13 CMV−), we evaluated associations among serum 25(OH)D levels, CMV serostatus, and cmvIL–10, the CMV–encoded interleukin–10 homolog that modulates host immune responses. While vitamin D insufficiency and CMV seropositivity were both highly prevalent, we found no statistically significant associations between 25(OH)D levels and CMV serostatus or cmvIL–10 levels. These findings highlight the need for further investigation into how vitamin D deficiency and CMV infection may independently or synergistically contribute to maternal and neonatal health disparities. Full article

Congenital cytomegalovirus (cCMV) infection is the most prevalent congenital infection, affecting approximately 0.5–2% of newborns, and is the leading non-genetic cause of sensorineural hearing loss and neurological impairment. The most severe outcome occurs following primary maternal infection during the first trimester of pregnancy, and up to 40–50% of affected fetuses sustain permanent damage. Diagnosis relies on early prenatal screening through maternal serum testing, optimally performed in the first trimester, followed by confirmatory amniocentesis after 17 weeks’ gestation. Prenatal imaging with ultrasound and magnetic resonance imaging (MRI) plays a critical role in the identification of fetal brain abnormalities. Prevention strategies emphasize hygiene measures aimed at reducing maternal exposure to bodily fluids of young children, particularly prior to conception and during early pregnancy. Despite progress in vaccine development, currently available ones demonstrate modest efficacy. This review presents a comprehensive summary of congenital CMV infection, addressing its epidemiology, pathogenesis, diagnostic approaches, clinical presentation, and preventive measures, with a focus on recent advances in vaccine research. Full article

Cytomegalovirus (CMV) represents the most prevalent cause of congenital viral infection in newborns and the leading non-genetic etiology of sensorineural hearing loss (SNHL) in children. Notably, only 10–15% of congenitally infected infants possibly present with classic clinical symptoms at birth, including Small for gestational age, Microcephaly, Petechiae or purpura, Blueberry muffin rash, Jaundice, Hepatomegaly, Splenomegaly and abnormal neurologic signs. In contrast, approximately 90% of infected neonates exhibit no apparent symptoms initially. Current research predominantly focuses on symptomatic cases due to their severe acute presentations and high rates of long-term sequelae (40–60%), including SNHL and neurodevelopmental impairments. However, significant controversy persists regarding the management of asymptomatic infants. Emerging evidence reveals that 8–15% of asymptomatic carriers develop Late-onset Hearing Loss (LOHL) beyond the neonatal period. Additionally, 5–10% may manifest neurodevelopmental abnormalities including mild intellectual disability, learning difficulties, or motor coordination disorders. Crucially, given the substantial population of asymptomatic cCMV cases, these delayed complications account for 30–40% of all cCMV-related long-term morbidity, underscoring their considerable public health impact. This review synthesizes current evidence and controversies regarding cCMV-related SNHL in asymptomatic or mildly symptomatic children, with a focus on screening, diagnostic classification, and antiviral management gaps, to heighten clinical awareness of this underrecognized cause of hearing loss. Full article

Background/Objectives: Neutropenia is a common adverse effect of oral valganciclovir (VGCV) treatment in infants with congenital cytomegalovirus infection (CCMVI), with an estimated prevalence of 20%. However, its clinical course and associated factors, including the influence of VGCV dosage, remain inadequately characterized. Methods: We conducted a single-center retrospective cohort study of infants treated with VGCV for symptomatic congenital CMV infection (CCMVI) at the Kobe University Hospital between 1 April 2009 and 31 March 2017. Detailed descriptive analyses of neutropenia were performed, and factors associated with its onset were explored using univariable logistic regression analyses. Results: A total of 31 patients were included, and neutropenia occurred in 35% of them during the 6-week treatment period. Its occurrence was observed throughout the treatment course, with no substantial difference in incidence between the 16 mg/kg/day and 32 mg/kg/day dosing groups. Neutropenia was more likely to occur in infants with shorter gestational age. Conclusions: Neutropenia occurred in 35% of patients during 6 weeks of VGCV treatment, irrespective of dosage, and was more common in those with shorter gestational age. Full article

Background/Objectives: Congenital cytomegalovirus (cCMV) infection is the most common non-genetic cause of sensorineural hearing loss (SNHL) in children. In cases of severe-to-profound SNHL, cochlear implantation (CI) is a widely used intervention, but outcomes remain variable due to possible neurodevelopmental comorbidities. This study aimed to evaluate the long-term auditory and language outcomes in children with cCMV after CI and to explore clinical and radiological predictors of post-CI performance. Methods: Fifty-three children with cCMV and bilateral severe-to-profound SNHL who underwent CI at five tertiary referral centers in Italy were included in the study. Auditory and language outcomes were assessed pre- and post-implantation using the Categories of Auditory Performance II (CAP-II) scale, the Nottingham 3-Level Classification, and the Bates Language Development Scale. Brain MRI abnormalities were classified according to the Alarcón classification. Correlations were explored between outcome scores and symptomatic status at birth, MRI findings, and neurodevelopmental comorbidities. Results: At birth, 40 children (75.5%) were symptomatic and 13 (24.5%) asymptomatic. Neurodevelopmental comorbidities were present in 19 children (35.8%). MRI was normal in 15 (28.3%), mildly abnormal in 26 (49%), and moderately to severely abnormal in 12 (22.6%). Auditory and language outcomes improved significantly post-CI (p < 0.001), though the outcomes varied widely. Twenty-five children (47%) reached CAP level ≥ 6, and thirteen (23%) reached Bates Level 6. Symptomatic status at birth correlated weakly with worse CAP (ρ = −0.291, p = 0.038) and Bates (ρ = −0.310, p = 0.028) scores. Higher Alarcón scores were significantly associated with neurodevelopmental comorbidities, though not directly with post-CI auditory and language outcomes. Finally, the presence of neurodevelopmental disabilities was generally associated with lower results, even if without statistical significance. Conclusions: CI provides substantial auditory and language benefit in children with cCMV, even in cases of severe neurodevelopmental comorbidities. MRI and developmental assessments, as well as perinatal history for clinical signs and symptoms, are helpful in guiding expectations and personalizing post-implantation support. Full article

Background: Human cytomegalovirus (HCMV) is the leading cause of congenital and acquired viral infections in newborns. While acquired infections are often asymptomatic, premature infants—especially those born before 30 weeks of gestation or with a very low birth weight (<1500 g)—are at an increased risk for severe infections. These can manifest as thrombocytopenia, liver failure, sepsis-like symptoms, and, in rare cases, death. HCMV is transmitted through various human secretions, including breast milk, which is the optimal feeding method for premature infants. Methods: We present five premature neonates, born between 23 and 26 weeks of gestation, each with a distinct clinical presentation of acquired HCMV infection. Results: All infants tested negative for congenital CMV infection via molecular urine testing within the first three weeks of life. Acquired infection was diagnosed between the second and third month of life, with symptoms such as septic shock, persistent thrombocytopenia, and signs of liver failure. Each infant received antiviral treatment along with regular viral load monitoring. Unfortunately, one patient died due to complications of prematurity. The remaining infants were discharged and continue to receive follow-up care in an outpatient clinic. Conclusions: These cases of postnatally acquired CMV infection aim to increase awareness of its highly heterogeneous and nonspecific clinical presentation, which may result in an incorrect, delayed, or concealed diagnosis. Currently, there are no clear guidelines on how to manage the presence of the virus in maternal breast milk, particularly for premature infants. It should be recommended to perform a molecular CMV test in all breast-fed preterm infants who present with sepsis-like symptoms, thrombocytopenia, liver failure, or other organ involvement. In case of a confirmed aCMV diagnosis, appropriate treatment should be introduced. Full article

Human cytomegalovirus (CMV) is the leading cause of congenital infections, often leading to mental retardation and neurological disorders. It is a major public health priority to develop a vaccine for preventing and controlling human CMV infection. In this report, we generated an oral Salmonella-based vaccine to express the M33 protein of murine cytomegalovirus (MCMV) and investigated the anti-MCMV immune responses induced in mice immunized with this vaccine. Compared to those administered with phosphate-buffered saline (PBS) or a control vaccine without M33 expression, mice immunized with the vaccine expressing the M33 protein exhibited a remarkable induction of antiviral serum IgG and mucosal IgA humoral responses and a significant elicitation of antiviral T cell responses. Successful inhibition of viral growth in lungs, spleens, livers, and salivary glands was also found in the vaccinated animals compared to the PBS-treated animals or those immunized with the control vaccine without M33 expression. Furthermore, substantial protection against MCMV challenge was observed in mice immunized with the vaccine. Thus, Salmonella-based vaccine expressing MCMV M33 can induce anti-MCMV effective immune responses and protection. Our study implies that attenuated Salmonella expressing human CMV antigens, including its homologue to M33, may represent promising oral anti-CMV vaccine candidates. Full article

Background: Cytomegalovirus (CMV) infection is the most common and serious congenital infection, with universal screening in pregnancy, standardized therapy, and a vaccine still lacking. Study design: In the 1990s, we noted that intravenous ganciclovir did not cure some children with severe sequelae due to congenital cytomegalovirus (CMV) infection. Therefore, we performed an open randomized trial using intravenous foscarnet as an alternative to intravenous ganciclovir in 24 infants (12 in each therapy group), all with severe neurological manifestations due to congenital CMV infection. Nine and five infants, belonging to the foscarnet or ganciclovir group, respectively, had abnormal hearing. One infant in each group also had chorioretinitis. Concomitantly, 12 CMV-infected infants with similar manifestations, who did not receive any therapy, were used as controls. The results of short-term (2 years) and long-term (7–29 years, mean 22.2) follow-up are reported herein. Short-term results: Neurological outcomes were normal in five of the twelve children who were treated with foscarnet, compared to nine of the twelve children given ganciclovir. None of the untreated children were healthy. There was a statistically significant difference (p = 0.023) between the treated and untreated children. Hearing was normal in four of the twelve children treated with foscarnet, seven of the twelve children treated with ganciclovir, and two untreated children. Long-term-results: Two children in both therapy groups died before the age of 17 years, and six untreated children died between 7 and 26 years of age. Neurological outcomes were normal in three of the ten children treated with foscarnet, in two of the ten treated with ganciclovir, and in none of the untreated children. Hearing was normal in two children treated with foscarnet, in six children treated with ganciclovir, and in one untreated child. Conclusions: Intravenous ganciclovir and foscarnet were found to be safe at long-term follow-up and appeared to be capable of mitigating the neurological and auditory consequences of congenital CMV disease at the short-term follow-up. However, there was progressive worsening of the symptomatology in all three groups, with a statistically significant increase in the number of deaths (p = 0.035) among 4 of the 24 children in the therapy groups and 6 of the 12 untreated children. Full article