T-Cell Immune Responses in Newborns and Long-Term Sequelae in Congenital Cytomegalovirus Infection (CYTRIC Study).

OBJECTIVE: The objective of this study was to assess the role of T-lymphocyte immune responses in newborns with congenital cytomegalovirus (CMV) infection (cCMV) and their potential association with the development of long-term sequelae. STUDY DESIGN: A multicenter, prospective study from 2017 to 2022 was conducted across 8 hospitals in Spain. Blood samples were collected within the first month of life from neonates diagnosed with cCMV. Intracellular cytokine staining was employed to evaluate the presence of CMV-specific interferon-gamma (IFN-γ)-producing CD8+ and CD4+ T lymphocytes (CMV-IFN-γ-CD8+/CD4+) using flow cytometry. The development of sequelae, including hearing loss and neurologic impairment, was assessed during follow-up. RESULTS: In total, 64 newborns were included; 42 infants (65.6%) had symptomatic cCMV. The median age at the last follow-up visit was 25.3 months (IQR 20.1-34.4). Eighteen infants had long-term sequelae (28.1%), predominantly hearing loss (20.3%) and neurologic disorders (15.6%). No relationship was observed between total count or percentage of CMV-specific IFN-γ-CD8+ or CD4+ lymphocytes and long-term sequelae. Multivariable analysis demonstrated an association between lower total lymphocyte count and long-term sequelae (aOR 0.549, 95% CI: 0.323-0.833), which requires further study. CONCLUSIONS: CMV-specific IFN-γ-CD4+ and CD8+ T-lymphocyte responses in neonates with cCMV were not predictive of long-term sequelae.

Clinical outcomes and antibody transfer in a cohort of infants with in utero or perinatal exposure to SARS-CoV-2 (Coronascope Study).

We aimed to describe the outcomes, focusing on the hearing and neurological development, of infants born to mothers with COVID-19 during pregnancy and to evaluate the persistence of maternal antibodies in the first months of life. An observational, prospective study at a tertiary hospital in Madrid (Spain) on infants born to mothers with COVID-19 during pregnancy between March and September 2020 was conducted. A follow-up visit at 1-3 months of age with a physical and neurological examination, cranial ultrasound (cUS), SARS-CoV-2 RT-PCR on nasopharyngeal swab, and SARS-CoV-2 serology were performed. Hearing was evaluated at birth through the automated auditory brainstem response and at six months of age through the auditory steady-state response. A neurodevelopmental examination using the Bayley-III scale was performed at 12 months of age. Of 95 infants studied, neurological examination was normal in all of them at the follow-up visit, as was the cUS in 81/85 (95%) infants, with only mild abnormalities in four of them. Serology was positive in 47/95 (50%) infants, which was not associated with symptoms or severity of maternal infection. No hearing loss was detected, and neurodevelopment was normal in 96% of the infants (median Z score: 0). CONCLUSION: In this cohort, the majority of infants born to mothers with COVID-19 during pregnancy were healthy infants with a normal cUS, no hearing loss, and normal neurodevelopment in the first year of life. Only half of the infants had a positive serological result during the follow-up. WHAT IS KNOWN: • Hearing loss and neurodevelopmental delay in infants born to mothers with COVID-19 during pregnancy has been suggested, although data is inconsistent. Maternal antibody transfer seems to be high, with a rapid decrease during the first weeks of life. WHAT IS NEW: • Most infants born to mothers with COVID-19 during pregnancy had normal hearing screening, cranial ultrasound, and neurodevelopmental status at 12 months of life. Antibodies against SARS-CoV-2 were only detected in 50% of the infants at two months of life.

Prevalence and Clinical Manifestations of Congenital Cytomegalovirus Infection in a Screening Program in Madrid (PICCSA Study).

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 value was 62.5% (CI 95%: 46.5%-76.1%). Two infants presented symptoms at birth. Eight (53.3%) children showed abnormalities in magnetic resonance imaging; most of them isolated white matter abnormalities. Newborns with abnormalities in magnetic resonance imaging showed higher viral loads in blood and saliva (P = 0.04). CONCLUSIONS: One in 200 neonates born in our hospital presented a cCMV infection. CMV viral load in saliva has been shown to be a simple and highly accepted screening method but should be confirmed by CMV detection in urine. In spite of the fact that half of infected children had abnormalities in cerebral imaging, diagnosis during the neonatal period would have been impossible without a screening program in most cases.

Diagnóstico precoz de la infección congénita por citomegalovirus: oportunidades perdidas / Early diagnosis of congenital cytomegalovirus infection: lost opportunities

Introducción: La infección por citomegalovirus (CMV) es la infección congénita más frecuente en Europa. El 10% de los niños infectados presentan síntomas al nacimiento, y hasta el 30-40% tienen algún grado de hipoacusia. Métodos Se ha realizado un estudio descriptivo retrospectivo incluyendo todos los pacientes diagnosticados de infección congénita por CMV fuera del período neonatal a lo largo de 4 años a partir de las muestras de sangre del talón en papel de filtro del cribado metabólico neonatal. Resultados Presentamos 5 pacientes diagnosticados de infección congénita por CMV fuera del periodo neonatal. Los principales motivos de consulta fueron la hipoacusia y/o el retraso psicomotor en los primeros meses de vida. Conclusión La infección por CMV puede ser poco sintomática al nacimiento y presentarse como un déficit auditivo y/o retraso psicomotor en la infancia. Es preciso un alto grado de sospecha para establecer un diagnóstico temprano que permita ofrecer tratamiento específico y mejorar el pronóstico a largo plazo (AU)

Introduction: Cytomegalovirus (CMV) infection is the most common congenital infection in Europe. Symptoms are present at birth in 10% of infected children, and up to 30-40% have some degree of hearing loss after the newborn period. Methods: A retrospective study was performed over a period of 4 years and included all patients with congenital CMV infection diagnosed after the neonatal period using the dried blood spots from neonatalmetabolic screening. Results: We present 5 patients diagnosed with congenital CMV infection outside the neonatal period. The main reasons for consultation were hearing loss and/or neurological impairment in the first few months of life. Discussion: Congenital CMV infection may be mildly symptomatic at birth, and present as hearing loss and/or neurological impairment in infancy. Therefore, a high degree of suspicion is necessary in order to make an accurate diagnosis and start specific treatment to improve the outcome (AU)

[Early diagnosis of congenital cytomegalovirus infection: lost opportunities]. / Diagnóstico precoz de la infección congénita por citomegalovirus: oportunidades perdidas.

INTRODUCTION: Cytomegalovirus (CMV) infection is the most common congenital infection in Europe. Symptoms are present at birth in 10% of infected children, and up to 30-40% have some degree of hearing loss after the newborn period. METHODS: A retrospective study was performed over a period of 4 years and included all patients with congenital CMV infection diagnosed after the neonatal period using the dried blood spots from neonatal metabolic screening. RESULTS: We present 5 patients diagnosed with congenital CMV infection outside the neonatal period. The main reasons for consultation were hearing loss and/or neurological impairment in the first few months of life. DISCUSSION: Congenital CMV infection may be mildly symptomatic at birth, and present as hearing loss and/or neurological impairment in infancy. Therefore, a high degree of suspicion is necessary in order to make an accurate diagnosis and start specific treatment to improve the outcome.

Imaging and clinical findings in patients with aberrant course of the cervical internal carotid arteries.

BACKGROUND AND PURPOSE: Aberrrant course of the cervical internal carotid arteries (ICAs) may result in submucosal masses in the posterior pharyngeal wall, may cause confusion at physical examination, may be symptomatic, and can be at risk of surgical injury. The aim of this report is to present the clinical and imaging characteristics associated with aberrant course of the cervical portion of the ICAs. METHODS: Imaging studies of 5.500 patients were prospectively selected from CT studies of the head and neck performed in a five years period, in which the course of the one or both ICAs at the level of the hypopharynx and oropharynx was assessed as aberrant by means of a proposed classification. We then reviewed the medical records to establish which symptoms were present and if these symptoms could be caused by these variations in the course of the ICAs. In selected cases, further studies including magnetic resonance (MR) imaging, MR angiography (MRA), or selective catheter angiography were obtained. RESULTS: In our restricted classification, we found 14 (0.2%) patients who met the cervical ICA aberrancy criteria. In all patients contrast enhanced CT or CT angiography was performed, 4 also have had MRI and MRA, and in two additional catheter angiograms were performed. Mean age was 62 years. Eight patients were male and seven were female. Four patients (28%) were considered to have clinical symptoms related to aberrant course of the ICAs. In most of the symptomatic patients both ICAs had aberrant courses. Overall, the course of the right ICA was aberrant in 43%, the left ICA in 14%, and both in 43%. In 50% of the cases the aberrancy of the artery was focal (localized to the oropharynx or laryngopharynx) and in the other 50% it involved the entire cervical course of the ICA. CONCLUSIONS: In most of our patients variations in the course of the cervical portion of the ICA involved the right side and were asymptomatic, except with regard to potential surgical risks. However, in about 25% of our patients these variations were thought to be the culprit of patient complaints, particularly oropharyngeal pulsatile sensation. Furthermore, extreme degrees of medialization of the ICAs resulted in progressive symptoms including hoarseness and upper respiratory distress.