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      The MRI spectrum of congenital cytomegalovirus infection

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          Abstract

          Human cytomegalovirus (CMV) is an ubiquitous pathogen, with a high worldwide seroprevalence. When acquired in the prenatal period, congenital CMV (cCMV) is a major cause of neurodevelopmental sequelae and hearing loss. cCMV remains an underdiagnosed condition, with no systematic screening implemented in pregnancy or in the postnatal period. Therefore, imaging takes a prominent role in prenatal diagnosis of cCMV. With the prospect of new viable therapies, accurate and timely diagnosis becomes paramount, as well as identification of fetuses at risk for neurodevelopmental sequelae. Fetal magnetic resonance imaging (MRI) provides a complementary method to ultrasound (US) in fetal brain and body imaging. Anterior temporal lobe lesions are the most specific finding, and MRI is superior to US in their detection. Other findings such as ventriculomegaly, cortical malformations and calcifications, as well as hepatosplenomegaly, liver signal changes and abnormal effusions are unspecific. However, when seen in combination these should raise the suspicion of fetal infection, highlighting the need for a full fetal assessment. Still, some fetuses deemed normal on prenatal imaging are symptomatic at birth or develop delayed cCMV‐associated symptoms, leaving room for improvement of diagnostic tools. Advanced MR sequences may help in this field and in determining prognosis, but further studies are needed.

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          Passive immunization during pregnancy for congenital cytomegalovirus infection.

          Currently, there is no effective intervention for a primary cytomegalovirus (CMV) infection during pregnancy. We studied pregnant women with a primary CMV infection. The therapy group comprised women whose amniotic fluid contained either CMV or CMV DNA and who were offered intravenous CMV hyperimmune globulin at a dose of 200 U per kilogram of maternal weight. A prevention group, consisting of women with a recent primary infection before 21 weeks' gestation or who declined amniocentesis, was offered monthly hyperimmune globulin (100 U per kilogram intravenously). In the therapy group, 31 women received hyperimmune globulin, only 1 (3 percent) of whom gave birth to an infant with CMV disease (symptomatic at birth and handicapped at two or more years of age), as compared with 7 of 14 women who did not receive hyperimmune globulin (50 percent). Thus, hyperimmune globulin therapy was associated with a significantly lower risk of congenital CMV disease (adjusted odds ratio, 0.02; 95 percent confidence interval, -infinity to 0.15; P<0.001). In the prevention group, 37 women received hyperimmune globulin, 6 (16 percent) of whom had infants with congenital CMV infection, as compared with 19 of 47 women (40 percent) who did not receive hyperimmune globulin. Thus, hyperimmune globulin therapy was associated with a significantly lower risk of congenital CMV infection (adjusted odds ratio, 0.32; 95 percent confidence interval, 0.10 to 0.94; P=0.04). Hyperimmune globulin therapy significantly (P<0.001) increased CMV-specific IgG concentrations and avidity and decreased natural killer cells and HLA-DR+ cells and had no adverse effects. Treatment of pregnant women with CMV-specific hyperimmune globulin is safe, and the findings of this nonrandomized study suggest that it may be effective in the treatment and prevention of congenital CMV infection. A controlled trial of this agent may now be appropriate. Copyright 2005 Massachusetts Medical Society.
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            Congenital cytomegalovirus infection following first trimester maternal infection: symptoms at birth and outcome.

            The relationship between gestational age at time of maternal cytomegalovirus (CMV) infection and outcome of fetal infection is not well defined because the timing of maternal infection is usually not known. To determine whether congenital cytomegalovirus (CMV) infection following primary maternal infection during the first trimester of pregnancy is more likely to lead to central nervous system (CNS) sequelae than fetal infection due to maternal infection later in pregnancy. Using serum collected during pregnancy from mothers of newborns with congenital CMV infection, maternal infection was categorized as first trimester (<13 weeks) or later based on dates and results of IgG and IgM assays for CMV antibody. Outcome of congenital CMV infection was assessed by longitudinal fotlow-up of the infected cohort. Sensorineural hearing loss was found in 8/34 (24%) of children in the first trimester group, compared with 1/40 (2.5%) in the later infection group (P=0.01, relative risk, 9.6). Considering any CNS sequela (hearing loss, mental retardation, cerebral palsy, seizures, chorioretinitis) 11/34 (32%) first trimester cases were affected compared with 6/40 (15%) in the later infection group (P=0.07, relative risk 2.2). None of the later group had more than one sequela, compared with 4 (12%) of the first trimester group (P=0.04). Children with congenital CMV infection following first trimester maternal infection are more likely to have CNS sequelae, especially sensorineural hearing loss, than are those whose mothers were infected later in pregnancy. However, some degree of CNS impairment can follow even late gestational infection.
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              Birth prevalence and natural history of congenital cytomegalovirus infection in a highly seroimmune population.

              The natural history of congenital cytomegalovirus (CMV) infection is scarcely known in populations with high maternal CMV seroprevalence. This study evaluated the birth prevalence, clinical findings at birth, and hearing outcome in CMV-infected children from such a population. Consecutively born infants were screened for the presence of CMV in urine and/or saliva specimens during the first 2 weeks after birth. Neonatal clinical findings were recorded, and CMV-infected children were tested to document hearing function during follow-up. A subset of mothers of CMV-infected infants were prenatally tested for the presence of anti-CMV immunoglobulin G antibodies. Congenital CMV infection was confirmed in 87 (1.08%; 95% confidence interval [CI], 0.86%-1.33%) of 8047 infants. Seven infants (8.1%; 95% CI, 3.3%-15.9%) had at least 1 clinical finding suggestive of CMV infection, and 4 (4.6%; 95% CI, 1.3%-11.3%) had >3 findings of systemic disease. Sensorineural hearing loss was found in 5 (8.6%; 95% CI, 2.9%-19.0%) of 58 children tested at a median age of 21 months. Bilateral profound hearing loss was observed in 2 children, and the hearing threshold was >60 decibels in all 5 children with hearing loss, including 2 children born to mothers with probable nonprimary CMV infection. The results of this large newborn screening study in a population with high CMV seroimmunity provide additional evidence that congenital CMV disease occurs in populations with high seroprevalence rates, with a similar incidence of CMV-related hearing loss to that reported in the offspring of women from populations in developed countries with lower rates of seroimmunity to CMV.
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                Author and article information

                Contributors
                mariana.cardoso.diogo@gmail.com
                Journal
                Prenat Diagn
                Prenat. Diagn
                10.1002/(ISSN)1097-0223
                PD
                Prenatal Diagnosis
                John Wiley & Sons, Ltd. (Chichester, UK )
                0197-3851
                1097-0223
                06 January 2020
                January 2020
                : 40
                : 1 ( doiID: 10.1002/pd.v40.1 )
                : 110-124
                Affiliations
                [ 1 ] Department of Image Guided Therapy University Clinic for Neuroradiology and Musculoskeletal Radiology, Medical University of Vienna Vienna Austria
                [ 2 ] Department of Pediatrics and Adolescent Medicine Medical University of Vienna Vienna Austria
                [ 3 ] Department of Obstetrics and Gynecology Medical University of Vienna Vienna Austria
                Author notes
                [*] [* ] Correspondence

                Mariana C Diogo, Department of Image Guided Therapy, University Clinic for Neuroradiology and Musculoskeletal Radiology, Medical University of Vienna, Währinger Gürtel 18‐20, 1090 Vienna, Austria.

                Email: mariana.cardoso.diogo@ 123456gmail.com

                Author information
                https://orcid.org/0000-0001-8459-910X
                https://orcid.org/0000-0002-0712-5282
                Article
                PD5591 PD-19-0340.R1
                10.1002/pd.5591
                7027449
                31802515
                0bfda058-d7f6-4d0d-9aa4-b4c77e42be34
                © 2019 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 26 July 2019
                : 16 September 2019
                : 07 October 2019
                Page count
                Figures: 7, Tables: 2, Pages: 15, Words: 10459
                Categories
                Special Issue Article
                Special Issue Articles
                Custom metadata
                2.0
                January 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.7.5 mode:remove_FC converted:18.02.2020

                Obstetrics & Gynecology
                Obstetrics & Gynecology

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