RESUMO
Cytomegalovirus is the most common cause of congenital infection worldwide. 90 % of children infected in utero are born without symptoms, but 15 % of them will develop disorders within the first five years of life. The most common disorders affect the inner ear, resulting in sensorineural hearing loss and/or vestibular dysfunction (VD). VD is often unrecognized and confused with conditions -affecting the central nervous system. It can cause delays in psychomotor development and predispose to overall developmental delay. Early diagnosis and treatment are essential to prevent or limit these sequelae. Antiviral treatment during the pre- and neonatal periods should be considered.
Le cytomégalovirus est la cause la plus fréquente d'infection congénitale dans le monde. 90 % des enfants infectés in utero naissent sans symptôme, mais 15 % d'entre eux vont développer des atteintes au cours des cinq premières années de vie. Les plus fréquentes touchent l'oreille interne, engendrant unesurdité neurosensorielle et/ou une dysfonction vestibulaire (DV). La DV est souvent méconnue et confondue avec des atteintes du système nerveux central. Elle peut provoquer des retards du développement psychomoteur et prédisposer à un retard global du développement. Un diagnostic et une prise en charge précoces sont essentiels pour prévenir ou limiter ces séquelles. Un traitement antiviral en période pré et néonatale doit être considéré.
Assuntos
Infecções por Citomegalovirus , Humanos , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/complicações , Recém-Nascido , Gravidez , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/etiologia , Perda Auditiva Neurossensorial/virologia , Perda Auditiva Neurossensorial/epidemiologia , Feminino , Complicações Infecciosas na Gravidez/diagnóstico , Doenças Vestibulares/diagnóstico , Doenças Vestibulares/epidemiologia , Doenças Vestibulares/etiologia , Antivirais/uso terapêuticoRESUMO
BACKGROUNDCongenital cytomegalovirus (cCMV) infection can cause developmental impairment and sensorineural hearing loss (SNHL). To determine the relationship between immune responses to cCMV infection and neurologic sequelae, T cell responses were compared for their connection to clinical symptoms at birth and neurodevelopmental outcomes.METHODSThirty cCMV-infected and 15 uninfected infants were enrolled in a single-center prospective observational case-control study. T cell pp65-specific cytokine responses; CD57, CD28, and PD-1 expression; and memory subsets were compared.RESULTSInfected neonates (73% symptomatic at birth) lacked pp65-specific cytokine-secreting T cells, with elevated frequencies of CD57+, CD28-, and PD-1+CD8+ T cells and effector memory subsets. Though frequencies overlapped between cCMV symptom groups, asymptomatic infants had higher frequencies of CD57+PD-1+CD8+ T cells. Neonates with subsequent developmental delay lacked detectable CMV-specific T cell responses, with patterns resembling those of uninfected infants. Two children with progressive SNHL had high frequencies of PD-1+CD8+ T cells over the first year compared with children without progressive SNHL.CONCLUSIONSimilar to published reports, neonatal viral antigen-specific cytokine-secreting T cell responses were not detected, but overall patterns indicate that globally differentiated memory CD8+ T cell populations were induced by cCMV infection, with higher frequencies of terminally differentiated PD-1+CD8+ T cells potentially associated with asymptomatic infection. In this cohort, a lack of in utero T cell differentiation was associated with developmental delay, and high frequencies of PD-1+CD8+ T cells persisted only in children with progressive SNHL. Further work is needed to define the specificity of these T cells and their mechanistic connection to these outcomes.FUNDINGThis study was funded through an intramural research award at Nationwide Children's Hospital, the Pediatric Infectious Disease Society Fellowship Award funded by Stanley and Susan Plotkin and Sanofi Pasteur, the Abigail Wexner Research Institute at Nationwide Children's Hospital, and the Pichichero Family Foundation Vaccines for Children Initiative Research Award from the Pediatric Infectious Diseases Society Foundation.
Assuntos
Linfócitos T CD8-Positivos , Infecções por Citomegalovirus , Humanos , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/complicações , Feminino , Estudos Prospectivos , Estudos de Casos e Controles , Recém-Nascido , Masculino , Lactente , Linfócitos T CD8-Positivos/imunologia , Citomegalovirus/imunologia , Perda Auditiva Neurossensorial/imunologia , Perda Auditiva Neurossensorial/virologia , Citocinas/metabolismo , Citocinas/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Receptor de Morte Celular Programada 1/imunologia , Linfócitos T/imunologia , Antígenos CD57/metabolismo , Antígenos CD57/imunologiaRESUMO
OBJECTIVE: To document the course of neonatal and short-term outcomes in pregnancies after first trimester CMV (cytomegalovirus) seroconversion and negative amniotic fluid (AF) CMV PCR. METHODS: We included 375 patients with a first-trimester CMV seroconversion and amniocentesis at ≥21 weeks. Termination of pregnancy (TOP) was offered in case antenatally severe CMV-related fetopathy was documented either by ultrasound or by MRI. AF CMV PCR-negative fetuses underwent a PCR CMV on neonatal urine (NU). Perinatal and short-term infant outcomes were investigated by a questionnaire, sent to parents. RESULTS: AF CMV PCR was positive in 118/375 cases (31.4%). TOP was performed in 46/118 (38.9%) and fetal demise occurred twice. Questionnaires were sent to 327 patients with an overall response rate of 77%. Three groups were considered: Group 1: the early infected group (AF CMV PCR positive; N=62), group 2: the late infected group (AF CMV PCR negative, NU CMV PCR positive; N=7) and group 3: the control group (AF+NU CMV PCR negative; N=160). Compared with group 3, group 1 was more frequently symptomatic at birth (6.2% vs 19.4%; p=0.006). In short-term follow-up, hearing impairment (23.5%; p<0.001), mild motor deficit - defined as abnormal early motor development or the need for physiotherapy in later life (21.6%; p=0.005) - and subnormal vision (15.7%; p=0.02) were significantly more frequent. Compared with group 3, group 2 showed more often jaundice (57.1%; p=0.04) and petechiae (28.6%; p=0.04) at birth, but other short-term symptoms were lacking. CONCLUSION: Although neonates may screen positive on urine for CMV after an AF CMV negative PCR, they show rarely and only mild sequelae in early life.
Assuntos
Infecções por Citomegalovirus , Transmissão Vertical de Doenças Infecciosas , Complicações Infecciosas na Gravidez , Primeiro Trimestre da Gravidez , Soroconversão , Humanos , Gravidez , Feminino , Infecções por Citomegalovirus/transmissão , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/congênito , Recém-Nascido , Complicações Infecciosas na Gravidez/virologia , Adulto , Citomegalovirus/imunologia , Citomegalovirus/isolamento & purificação , Amniocentese , Líquido Amniótico/virologia , Reação em Cadeia da Polimerase , Resultado da Gravidez/epidemiologia , MasculinoRESUMO
OBJECTIVE: Congenital cytomegalovirus infection (cCMV) is a common, frequently unrecognized cause of childhood disability. The aim of the present study was to determine the symptoms that raise the suspicion of cCMV, define the neurodevelopmental outcomes, and assess their correlations. METHODS: This longitudinal observational study comprised 78 children with symptomatic cCMV who underwent neuropediatric follow-up for 4 to 17.9 years. RESULTS: Symptoms of central nervous system involvement, hearing/visual impairments, and hepatic involvement were mostly recognized. The average age of disease suspicion was 3.3 months. In terms of outcomes, 10.53% of the children developed complex minor neurological dysfunction and 23.68% developed cerebral palsy. Visual and hearing impairments occurred in 38.16% and 14.47% of patients, respectively. Intellectual disability was present in 30.26% of patients, and epilepsy in 21.05%. Microcephaly and hearing impairment was significantly associated with overall neurodevelopmental outcome. Microcephaly was also associated with poor motor outcomes, hearing impairment, and severe visual impairment. Furthermore, microcephaly and intrauterine growth restriction were significantly associated with poor cognitive outcomes. CONCLUSION: Symptoms that raised the suspicion of cCMV-especially microcephaly, hearing impairment, and intrauterine growth restriction-were important parameters that were associated with outcomes; however, their recognition was often insufficient and/or late.
Assuntos
Infecções por Citomegalovirus , Humanos , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/diagnóstico , Feminino , Masculino , Criança , Pré-Escolar , Lactente , Adolescente , Estudos Longitudinais , Microcefalia/virologia , Microcefalia/etiologia , Paralisia Cerebral , Perda Auditiva/virologia , Perda Auditiva/etiologia , Perda Auditiva/diagnóstico , Deficiência Intelectual/virologia , Retardo do Crescimento Fetal/virologia , Transtornos da Visão/virologia , Transtornos da Visão/etiologia , Transtornos da Visão/diagnóstico , Recém-Nascido , Prognóstico , Citomegalovirus/patogenicidade , SeguimentosRESUMO
PURPOSE OF REVIEW: The purpose of this review is to summarize the very recent literature surrounding hearing outcomes of children with congenital cytomegalovirus (cCMV) detected through systematic screening programs. RECENT FINDINGS: There are several different approaches to cCMV screening including forms of targeted vs. universal screening of newborns as well as maternally-derived prenatal testing. However, many studies fail to document hearing-related outcomes both in the newborn period and further into childhood when late-onset sensorineural hearing loss (SNHL) can occur. This systematic review included studies of neonates screened for cCMV reporting hearing outcomes for at least one point in time. Hearing targeted screening appeared the most widely reported for detection of unilateral and bilateral SNHL in those with cCMV. A few studies examined these clinical findings in relation to antiviral treatment. SUMMARY: Congenital CMV is an important and common cause of childhood hearing loss. Newborn screening programs may expand opportunities for early diagnosis and treatment of the infection and its sequelae.
Assuntos
Infecções por Citomegalovirus , Perda Auditiva Neurossensorial , Triagem Neonatal , Humanos , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/complicações , Recém-Nascido , Perda Auditiva Neurossensorial/virologia , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/congênito , Testes AuditivosRESUMO
Cytomegalovirus (CMV) infection, which mostly causes a subclinical infection early in life, has important clinical consequences in certain patient groups. CMV is the most common congenital infection and can cause permanent disabilities such as hearing loss and motor- and cognitive deficits in affected infants. In allogeneic haematopoietic stem cell and solid organ transplant recipients, CMV still is an important infectious complication with a risk for life-threatening disease. The previous Swedish recommendations for the management of CMV infections were updated by an expert group under the guidance of The Swedish Reference Group for Antiviral Treatment (RAV) and published at the website of RAV in August 2023 (https://www.sls.se/rav/rekommendationer/cytomegalovirus/). We here provide a translation of the updated recommendations, with minor modifications regarding diagnosis of CMV pneumonia. In the present recommendations, we discuss aspects of old and new CMV antivirals, including dosing for different age groups, and cover the management of congenital infections and CMV in immunocompromised patients. The recommendations are evidence-graded in accordance with the Oxford Centre for Evidence-Based Medicine.
Assuntos
Antivirais , Infecções por Citomegalovirus , Humanos , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/congênito , Antivirais/uso terapêutico , Suécia , Hospedeiro Imunocomprometido , Citomegalovirus , Lactente , Feminino , Transplante de Células-Tronco Hematopoéticas , Recém-NascidoRESUMO
BACKGROUND: The treatment of congenital cytomegalovirus (CMV) infection is usually administered to neonates after birth; however, it can be anticipated during the prenatal period by treating pregnant women in order to reduce the severity of the congenital disease. The most commonly used treatment for CMV during pregnancy is valaciclovir; however, valganciclovir has a higher potency against CMV and is the first choice for neonates with congenital CMV disease. OBJECTIVES: We investigated neonatal and maternal safety of tertiary prevention in infected fetuses showing ultrasound features of infection using valganciclovir. METHODS: Retrospective cohort study of pregnant women and their symptomatic infected fetuses taking valganciclovir, 3â×â450 mg per day. All fetuses presented at least one prenatal feature on ultrasound. We assessed fetal/neonatal and maternal safety, as well as neonatal efficacy of treatment. The main outcome was neutropenia. Secondary outcomes included other haematological side effects, symptoms at birth and neonatal CMV-PCR was positive. RESULTS: Seventeen women with singleton pregnancies received valganciclovir from a median (IQR) of 27.1 (26.0-30.3) to 11.6 (6.5-12.9) weeks of gestation. No neonatal neutropenia was reported. One pregnancy was terminated for severe features. Three newborns (18%) were asymptomatic at birth, including one with negative CMV-PCR from blood and saliva. CMV-PCR was positive for 12/13 symptomatic newborns, with a median (IQR) log10 viral load of 3.36 (3.30-4.20), 4.03 (1.75-4.27) and 3.04 (0.00-3.40) log10 copies/mL in blood, urine and saliva, respectively. CONCLUSIONS: Tertiary prevention by valganciclovir appears to be well tolerated for both fetus and mother. However, more extensive trials accompanied by long-term follow-up are needed.
Assuntos
Antivirais , Infecções por Citomegalovirus , Complicações Infecciosas na Gravidez , Valganciclovir , Humanos , Valganciclovir/uso terapêutico , Valganciclovir/administração & dosagem , Valganciclovir/efeitos adversos , Feminino , Gravidez , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/congênito , Antivirais/uso terapêutico , Antivirais/efeitos adversos , Antivirais/administração & dosagem , Estudos Retrospectivos , Recém-Nascido , Adulto , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/virologia , Resultado do Tratamento , Citomegalovirus/efeitos dos fármacos , Ganciclovir/análogos & derivados , Ganciclovir/uso terapêutico , Ganciclovir/efeitos adversos , Transmissão Vertical de Doenças Infecciosas/prevenção & controleRESUMO
OBJECTIVE: To understand parental perspectives regarding universal newborn screening (UNS) for congenital cytomegalovirus (cCMV) in Canada. DESIGN: A qualitative, patient-led study using the Patient and Community Engagement Research approach consisting of online focus groups and in-depth individual interviews to understand parental preferences regarding UNS for cCMV. Data were analysed iteratively using inductive thematic analysis and narrative story analysis. SETTING: Canada-wide study conducted via video conference from October to December 2023. PATIENTS: 12 participants from five Canadian provinces who self-identified as 18 years of age or older and as having parental lived experience with cytomegalovirus (CMV) or cCMV participated in the study. RESULTS: We identified three themes: (1) attitudes about UNS for cCMV, including participants' unanimous support for UNS and confirmation that parental anxiety is not a deterrent for screening, (2) cCMV diagnosis, including the importance of coupling cCMV diagnosis with access to treatment and medical support and (3) awareness of cCMV, where participants shared their frustration about the lack of public and pregnant people's awareness of cCMV. CONCLUSIONS: Parental anxiety is not a deterrent for UNS for cCMV. Children with cCMV and their families deserve every opportunity to attain their best possible outcomes. UNS offers children with cCMV access to early intervention if they need it, and also helps to raise awareness and education to prevent future CMV infections.
Assuntos
Infecções por Citomegalovirus , Triagem Neonatal , Pais , Pesquisa Qualitativa , Humanos , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/diagnóstico , Canadá/epidemiologia , Triagem Neonatal/métodos , Feminino , Pais/psicologia , Recém-Nascido , Masculino , Adulto , Grupos Focais , Conhecimentos, Atitudes e Prática em SaúdeRESUMO
INTRODUCTION: This prospective cohort study aims to investigate the hearing dynamics and the changes in the central auditory pathways in infants with congenital cytomegalovirus (cCMV) infection. MATERIALS AND METHODS: cCMV-infected neonates aged ≤3 weeks old were recruited and underwent clinical and laboratory tests to detect viremia and symptomatic infection, hearing examinations at three and six months of age, and radiological imaging of brain auditory pathways using diffusion tensor imaging. RESULTS: From 26 eligible infants (52 ears), we detected symptomatic infection in nine (34.6%), viremia in 14 (14/25; 56.0%) and sensorineural hearing loss (SNHL) in 14 infants (53.8%). We observed 40 ears (76.9%) with unstable hearing thresholds, 17 (42.5%) of which fluctuated. Hearing fluctuation and progressivity were more common in symptomatic infection (66.7% vs. 14.7%, p<0.001; and 38.9% vs. 2.9%, p=0.002; respectively). A substantial proportion of ears had reduced fractional anisotropy (FA) in the medial geniculate body (59.1%), superior olivary nucleus (45.5%), trapezoid body (40.9%), auditory radiation (36.4%) and inferior colliculus (31.8%). Symptomatic infection was associated with an increased FA in the medial geniculate body (mean difference, MD: 0.12; 95% Confidence Intervals, 95%CI: 0.03, 0.22) and viremia in the inferior colliculus (MD: 0.09; 95%CI: 0.02, 0.16). An FA in the inferior colliculus of ≥0.404 had a sensitivity and specificity of 68.8% and 83.3% in predicting viremia (area under the curve 0.823; 95%CI: 0.633, 1.000, p=0.022). CONCLUSION: SNHL along with its fluctuation and progression are common in cCMV-infected infants. cCMV infection may induce structural changes in the central auditory pathway.
Assuntos
Vias Auditivas , Infecções por Citomegalovirus , Humanos , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/diagnóstico por imagem , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/fisiopatologia , Estudos Prospectivos , Feminino , Masculino , Recém-Nascido , Vias Auditivas/diagnóstico por imagem , Vias Auditivas/fisiopatologia , Perda Auditiva Neurossensorial/etiologia , Perda Auditiva Neurossensorial/virologia , Perda Auditiva Neurossensorial/fisiopatologia , Perda Auditiva Neurossensorial/diagnóstico por imagem , Lactente , Testes AuditivosRESUMO
This study aimed to retrospectively evaluate the baseline and follow-up viral loads and viral clearance times in cases followed for asymptomatic and symptomatic congenital cytomegalovirus (cCMV) infection between August 2010 and August 2022. Among 93 cases, they had asymptomatic (n: 55) and symptomatic (n: 38). The median baseline blood viral load detected in the symptomatic cCMV (ScCMV) infection (13 054 IU/mL) was significantly higher than that of asymptomatic cCMV (AcCMV) infection (4636 IU/mL) (p < 0.013). There was no difference in median viral clearance times (75 and 90 days, respectively) in baseline viremic cases in the ScCMV and AcCMV infection groups. There were no differences in median baseline blood viral load (6930 IU/mL and 14 268 IU/mL, respectively) and median viral clearance times (75 and 85 days, respectively) between the 6-week and 6-month antiviral treatment group. No correlation was found between baseline blood viral load, clinical severity, and the number of systems involved. However, in initial viremic cases, the viral load threshold for a symptomatic case was 8856 IU/mL, with 85.7% sensitivity and 54.5% specificity.
Assuntos
Infecções por Citomegalovirus , Citomegalovirus , Carga Viral , Humanos , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/virologia , Infecções por Citomegalovirus/sangue , Infecções por Citomegalovirus/diagnóstico , Estudos Retrospectivos , Feminino , Masculino , Recém-Nascido , Citomegalovirus/isolamento & purificação , Citomegalovirus/genética , Infecções Assintomáticas , Lactente , Antivirais/uso terapêutico , Viremia/virologiaRESUMO
Cytomegalovirus causes the most common congenital infection worldwide. With most infants asymptomatic at birth, the few affected may present with variable clinical scenarios, from isolated hearing loss to severe neurologic impairment. Public health interventions include all actions at the health system, community, and individual levels that aim at reducing the burden of congenital Cytomegalovirus. This review examines the literature on maternal and neonatal screening programs in light of current evidence for treatment and the development of vaccines against Cytomegalovirus. Potential biases and benefits of these interventions are outlined, with the objective of increasing awareness about the problem and providing readers with data and critical tools to participate in this ongoing debate.
Assuntos
Infecções por Citomegalovirus , Citomegalovirus , Saúde Pública , Humanos , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/prevenção & controle , Recém-Nascido , Gravidez , Feminino , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Complicações Infecciosas na Gravidez/virologia , Complicações Infecciosas na Gravidez/prevenção & controle , Complicações Infecciosas na Gravidez/epidemiologia , Triagem NeonatalAssuntos
Infecções por Citomegalovirus , Triagem Neonatal , Humanos , Recém-Nascido , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/epidemiologia , Minnesota/epidemiologia , Vigilância da População , Citomegalovirus/isolamento & purificaçãoRESUMO
OBJECTIVES: Congenital Cytomegalovirus (cCMV) has been associated with hearing, vision, and neurodevelopmental long-term sequelae. Despite the social burden associated with the disease, a universally accepted consensus on screening, diagnostic, therapeutic and follow-up approaches has not been reached. The present observational retrospective study aims at describing long-term sequelae and radiological abnormalities associated with cCMV in children early identified by extended hearing-targeted screening and evaluated by audiological follow-up in a single III Level Audiological Referral Center for at least 2 years. METHODS: Audiological neonatal and follow-up data were available for all subjects. Data collection included clinical neonatal and virological assessment at birth. Ophthalmological, neurodevelopmental and neuroradiological follow-up abnormalities compatible with cCMV sequelae were collected by clinical reports. Spearman's rank correlation coefficient (rho-ρ) was used to evaluate possible correlations among the considered parameters. RESULTS: 61 newborns were identified by extended hearing-targeted cCMV screening and diagnosed mostly (83.6 %) by PCR viral DNA extraction in urine collected within the 15° day of life. Seventeen babies were born preterm, with a mean gestational age of 33.5 weeks. Sixteen patients (26.2 %) were admitted to an Intensive or sub-Intensive Neonatal Care Unit. At birth, 35 newborns were symptomatic (57.3 %), and 19 of them received antiviral treatment by valganciclovir or ganciclovir. Overall, 20 children (32.7 %) were diagnosed with sensorineural hearing loss (SNHL), among them 17 (85 %) were refer at the newborn hearing screening while 3 (15 %) were Pass. 5/20 children (25 %) presented isolated SNHL, while in 15/20 (75 %) children SNHL was associated to other long-term sequelae. In 5 patients (25 %) a progression of the hearing threshold was observed, with a mean age of progression of 26 months of age. Risk factors for progression were a worse final hearing threshold (Spearman's ρ = 0.434; p = 0.0001) and a worse hearing threshold at birth (Spearman's ρ = 0.298; p = 0.020). Thirteen children were fitted with hearing aids, 8 of whom subsequently underwent cochlear implantation. Concerning long term impairments, 10/61 children (17 %) presented a variety of ophthalmological sequelae, while 16/40 cCMV patients (40 %) were diagnosed with neurodevelopmental abnormalities. Language delays were significantly associated with a worse hearing threshold (ρ = 0.582; p = 0.0001) and with other neurocognitive abnormalities (ρ = 0.677, p = 0.0001). 30 children underwent radiological brain evaluation by Magnetic Resonance Imaging, and 63.3 % of them presented abnormalities compatible with cCMV. Mean viral load at birth did not show significant associations with long-term sequelae. CONCLUSIONS: The study highlights the diverse and significant long-term sequelae of cCMV infection detected through early screening. With a significant proportion of cCMV children developing sensorineural hearing loss, ophthalmological and neurodevelopmental issues, the results emphasize the importance of continuous, multidisciplinary follow-up. Early identification and tailored interventions are crucial for improving the long-term health and quality of life of children affected by cCMV.
Assuntos
Infecções por Citomegalovirus , Triagem Neonatal , Humanos , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/complicações , Estudos Retrospectivos , Feminino , Masculino , Recém-Nascido , Triagem Neonatal/métodos , Pré-Escolar , Lactente , Seguimentos , Testes Auditivos , Antivirais/uso terapêuticoRESUMO
BACKGROUND: Early diagnosis of congenital CMV infection (cCMVI) allows for early intervention and follow-up to detect delayed hearing loss. While CMV PCR in urine is the gold standard for cCMVI diagnosis, saliva testing is often performed. OBJECTIVES: Our aim was to determine (i) if swab saliva sampling needed standardization, (ii) if a threshold value in "virus copies per million cells (Mc)" in saliva samples could improve clinical specificity, and (iii) to establish a correlation between viral load in saliva and symptomatology/outcome of cCMVI. MATERIALS AND METHODS: In our institution, universal newborn screening is performed on saliva swabs at delivery or until day 3 of life. If positive, CMV PCR in urine is done within 2 weeks to confirm or exclude cCMVI. RESULTS: Cell quantification showed that saliva swab sampling was well performed as 95.4 % samples had more than 100 cells/10 µL. There was a good correlation between saliva viral load in copies/mL and in copies/Mc (Pearson's r = 0.96, p < 0.0001). However, threshold values, established to determine a viral load level at which we could confidently identify infected newborns, did not improve positive predictive value (21.8 % for copies/mL and 21 % for copies/Mc vs 25.4 % without threshold) but instead reduced sensitivity (88 % and 85% vs 100 % without threshold). Samples collected on day 2 or 3 had better positive predictive value (38.7 %) compared to those collected on day 1 (23.8 %). Symptomatology at birth was not significantly associated with viral load in saliva at diagnosis. However, sequelae occurrence was associated with viral load in saliva (copies/Mc). DISCUSSION: Our results confirm that saliva swab is a suitable sample for universal neonatal screening. However, identifying newborns that will develop sequelae remains an issue in the management of cCMVI.
Assuntos
Infecções por Citomegalovirus , Triagem Neonatal , Valor Preditivo dos Testes , Saliva , Sensibilidade e Especificidade , Manejo de Espécimes , Carga Viral , Humanos , Saliva/virologia , Recém-Nascido , Triagem Neonatal/métodos , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/virologia , Manejo de Espécimes/métodos , Citomegalovirus/isolamento & purificação , Citomegalovirus/genética , Feminino , Masculino , Diagnóstico Precoce , Estudos de ViabilidadeRESUMO
Cytomegalovirus (CMV) is the leading infectious cause of brain defects and neurological dysfunctions, including sensorineural hearing loss (SNHL). Targeted screening in neonates failing the hearing screen is currently recommended in Italy according to national guidelines. However, SNHL may not be present at birth; also, congenital CMV (cCMV) may manifest with subtle signs other than SNHL. Therefore, the inclusion of additional criteria for cCMV screening appears clinically valuable. Starting January 2021, we have implemented expanded targeted cCMV screening at our center, with testing in case of maternal CMV infection during pregnancy, inadequate antenatal care, maternal HIV infection or immunosuppression, birthweight and/or head circumference < 10th centile, failed hearing screen, and prematurity. During the first three years of use of this program (2021-2023), 940 (12.3%) of 7651 live-born infants were tested. The most common indication was birthweight < 10th centile (n = 633, 67.3%). Eleven neonates were diagnosed as congenitally infected, for a prevalence of 1.17% (95%CI 0.48-1.86) on tested neonates and of 0.14% (95%CI 0.06-0.23) on live-born infants. None of the cCMV-infected newborns had a failed hearing screen as a testing indication. Implementation of an expanded cCMV screening program appears feasible and of clinical value.
Assuntos
Infecções por Citomegalovirus , Citomegalovirus , Triagem Neonatal , Complicações Infecciosas na Gravidez , Humanos , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/diagnóstico , Recém-Nascido , Feminino , Triagem Neonatal/métodos , Gravidez , Itália/epidemiologia , Citomegalovirus/genética , Citomegalovirus/isolamento & purificação , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/virologia , Masculino , Perda Auditiva Neurossensorial/virologia , Perda Auditiva Neurossensorial/diagnóstico , PrevalênciaRESUMO
Objective: To assess the clinical features and effectiveness of antiviral therapy in newborns with sensorineural hearing loss (SNHL) caused by congenital congenital cytomegalovirus (cCMV) infection, and to speculate the risk factors for poor hearing outcomes. Methods: A multicenter prospective cohort study wasconducted, enrolling 176 newborns diagnosed with cCMV at four research centers in Zhejiang Province from March 1, 2021, to April 30, 2024. Clinical characteristics at birth were recorded and hearing was followed up. The children were divided into groups based on their condition at birth, specifically into asymptomatic, mild symptom, and moderate to severe symptom groups. Additionally, they were divided into SNHL and normal hearing groups based on the results of air conduction brainstem audiometry at birth. And they were also divided into treatment and untreated groups according to antiviral treatment. Mann Whitney U test, and chi square test were used for inter group comparison to analyze the differences in clinical features between different disease groups, and to analyze the effects of clinical features, antiviral therapy, and other factors on hearing improvement. Logistic regression analysis was employed to identify the risk factors influencing hearing outcomes. Results: Among the cohort of 176 children diagnosed infection with cCMV, 90 cases were male and 86 cases were female. Of these, 79 cases were asymptomatic, 12 cases classified as mild cCMV and 85 cases as moderate to severe cCMV. Fifty cases belonged to SNHL group, with different degrees of severity, including 30 cases of mild, 9 cases of moderate, 5 cases of severe, and 6 cases of extremely severe SNHL. Among the 121 cases in the normal hearing group, 2 cases (1.7%) exhibited late-onset hearing loss despite having normal hearing at birth. Among 81 cases (46.0%) who completed the hearing follow-up, 71 cases (87.7%) had good hearing outcomes and 10 cases (12.3%) had poor hearing outcomes. Among the 81 children, 29 cases (35.8%) had SNHL at birth. During follow-up, the hearing threshold improved in 19 cases (65.5%), remained stable in 7 cases (24.1%) and progressed in 3 cases (10.3%). A total of 26 cases in the treatment group and 55 cases in the untreated group completed the hearing follow-up assessment. The rate of hearing improvement in the treatment group was found to be higher compared to the untreated group (13 cases (50.0%) vs. 6 cases (10.9%), χ2=15.00, P<0.01), with individuals in the treatment group having a 4.58 times greater likelihood of experiencing hearing improvement (RR=4.58,95%CI 1.96-10.70, P<0.05). However, no statistically significant difference was observed in hearing outcomes between the antiviral treatment group and the untreated group (RR=0.90, 95%CI 0.57-1.41, P=0.517). Multivariate analysis further confirmed SNHL (OR=11.58, 95%CI 2.10-63.93, P=0.005) and preterm birth (OR=4.98, 95%CI 1.06-23.41, P=0.042) as independent risk factors for poor hearing outcomes. Conclusions: SNHL resulting from cCMV infection presents symptoms at birth and can be improved by antiviral therapy. Poor hearing outcomes are associated with SNHL and prematurity.
Assuntos
Antivirais , Infecções por Citomegalovirus , Perda Auditiva Neurossensorial , Humanos , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/complicações , Masculino , Feminino , Recém-Nascido , Estudos Prospectivos , Perda Auditiva Neurossensorial/virologia , Perda Auditiva Neurossensorial/etiologia , Antivirais/uso terapêutico , Fatores de Risco , Citomegalovirus , Lactente , Modelos LogísticosRESUMO
Congenital cytomegalovirus (cCMV) is among the most common congenital infections globally. Of 85%-90% cCMV-infected infants without symptoms at birth, 10%-15% develop sequelae, most commonly sensorineural hearing loss (SNHL); their childhood neurodevelopmental outcomes are less well understood. Embase and MEDLINE were searched for publications from 16th September 2016 to 9th February 2024 to identify studies reporting primary data on neurodevelopmental outcomes in children with asymptomatic cCMV (AcCMV), measured using assessment tools or as evaluated by the study investigators, clinicians, educators, or parents. The Newcastle-Ottawa scale was applied to studies to assess risk of bias. Of 28 studies from 18 mostly high-income countries, there were 5-109 children with AcCMV per study and 6/28 had a mean or median age at last follow-up of ≥5 years. Children with AcCMV had better neurodevelopmental outcomes than children with symptomatic cCMV in 16/19 studies. Of 9/28 studies comparing AcCMV with CMV-uninfected children, six reported similar outcomes whilst three reported differences limited to measures of full-scale intelligence and receptive vocabulary among children with AcCMV and SNHL, or more generally in motor impairment. Common limitations of studies for our question were a lack of cCMV-uninfected controls, heterogeneous definitions of AcCMV, lack of focus on neurodevelopment, selection bias and inadequate follow-up. There was little evidence of children with AcCMV having worse neurodevelopmental outcomes than CMV-uninfected children, but this conclusion is limited by study characteristics and quality; findings highlight the need for well-designed and standardised approaches to investigate long-term sequelae.
Assuntos
Infecções Assintomáticas , Infecções por Citomegalovirus , Humanos , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/virologia , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/diagnóstico , Infecções Assintomáticas/epidemiologia , Recém-Nascido , Transtornos do Neurodesenvolvimento/virologia , Criança , Lactente , Pré-Escolar , Perda Auditiva Neurossensorial/virologia , CitomegalovirusRESUMO
Cytomegalovirus, one of the most common congenital viruses in neonates, is represented within the TORCH acronym, which signifies its ability to be transmitted vertically to the fetus during maternal infection. Despite advances in prenatal diagnostics, CMV is still the leading cause of congenital infection in neonates, with a 0.64% prevalence. Additionally, the virus causes the majority of non-genetic hearing deficits, abnormal neurologic development, and other permanent disabilities seen in neonates. This primer describes the presentation, diagnosis, and treatment of congenital infection to benefit providers who work with women during the perinatal period as well as neonates and pediatric patients.
Assuntos
Infecções por Citomegalovirus , Transmissão Vertical de Doenças Infecciosas , Feminino , Humanos , Recém-Nascido , Gravidez , Antivirais/uso terapêutico , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/congênito , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/terapiaRESUMO
Background/aim: Cytomegalovirus (CMV) is the most common congenital viral infection. Although most children with congenital CMV (approximately 85%-90%) are asymptomatic at birth, findings such as sensorineural hearing loss, microcephaly, and neurodevelopmental retardation can be observed during the follow-up. Among the brain magnetic resonance imaging (MRI) findings of CMV are white matter abnormalities, polymicrogyria, and periventricular calcification. Since a definitive diagnosis of congenital CMV cannot be made after the neonatal period, the identification of the associated phenotype is diagnostically important, but data are limited in patients who have been retrospectively diagnosed with congenital CMV infection. The aim of this study was to evaluate the short- and long-term neurological follow-up results of congenital CMV infections in a tertiary hospital. Materials and methods: The neurological results of fifteen patients under the age of 18 years, who had a definitive diagnosis of congenital CMV infection and were followed up in a tertiary care hospital between 2011 and 2020, were retrospectively evaluated. Results: Ten of the patients in our study group were male. The mean age at presentation for neurological evaluation was 2.02 ± 1.54 months, with a median follow-up time of 36.3 months (range: 9.3-129.4 months). Neurological disorders detected during the long-term follow-up included cerebral palsy (46.7%), cognitive impairment (46.7%), epilepsy (40%), and sensorineural hearing loss (26.7%). The most common abnormality observed on MRI scans was white matter involvement (53.3%). Conclusion: Early diagnosis and intervention are crucial in congenital CMV infection, as it commonly results in neurological involvement among the patients in our series. This preventable condition warrants further research regarding prenatal/neonatal screening.
Assuntos
Infecções por Citomegalovirus , Imageamento por Ressonância Magnética , Humanos , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/diagnóstico por imagem , Masculino , Feminino , Estudos Retrospectivos , Lactente , Recém-Nascido , Pré-Escolar , Criança , Perda Auditiva Neurossensorial/virologiaRESUMO
BACKGROUND: Congenital cytomegalovirus (cCMV) is the most common infectious cause of neurodevelopmental deficits in US children. To inform patient management, it is important to define whether central nervous system (CNS) manifestations are present at birth. This study characterized neuroimaging findings in infants with cCMV identified by a universal screening study in Minnesota during February 2016-December 2022. METHODS: Newborns with cCMV infection (confirmed by urine CMV polymerase chain reaction [PCR] testing, obtained following a positive screening saliva and/or dried blood spot result) underwent a diagnostic evaluation that included a cranial ultrasound (cUS) exam, laboratory studies, ophthalmological, and audiological evaluation. Neuroimaging findings and cCMV disease classification were interpreted based on international consensus guidelines. RESULTS: Among 87 newborns with confirmed cCMV, 76 underwent cUS. Of these, 53/76 (70%) had normal examinations, while 23/76 (30%) exhibited cUS findings: for 5 infants, these were clearly cCMV disease-defining, while for 18 infants, there were findings of uncertain significance. Magnetic resonance imaging (MRI) results (nâ =â 10 infants) aligned with cUS cCMV disease-defining findings in 2 infants, while cCMV-specific abnormalities were noted by MRI in 2 of 6 infants with nondiagnostic/incidental cUS findings. Of 9 infants who had both cUS and MRI examination, the average time interval between studies was 220 days (range, 2-1061). Excluding infants with cCMV CNS disease-defining cUS abnormalities, incidental findings were observed more commonly in infants with clinical/laboratory features described in cCMV disease classification guidelines (9/13) than in newborns with completely asymptomatic infections (9/58; Pâ <â .0001). CONCLUSIONS: Among infants with cCMV identified in a universal screening study, the majority had a normal cUS. CNS disease-defining abnormalities were present in 7%, while 24% had findings of uncertain significance. We propose that many cUS findings are incidental, and not diagnostic of symptomatic cCMV infection. Although these findings may not be sufficient to define the presence of symptomatic cCMV disease involving the CNS, in our study they were more commonly observed in infants with other clinical and/or laboratory findings associated with symptomatic cCMV infection.