Frequeny of CMV Testing During Pregnancy- A Retrospective Study

Frequeny of CMV Testing During Pregnancy- A Retrospective Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Frequeny of CMV Testing During Pregnancy- A Retrospective Study Antigoni Hadjiiona, Ioannis Michaelides, Peter Kummer, Maurice Kappelmeyer, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5227922/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 31 Jan, 2025 Read the published version in Archives of Gynecology and Obstetrics → Version 1 posted 5 You are reading this latest preprint version Abstract Purpose The cytomegalovirus (CMV) belongs to the family of human Herpesviridae and is distributed worldwide. It is the most common cause of viral congenital infections and can have serious consequences for the health of the fetus in the event of a vertical infection. The aim of this study is to evaluate the frequency of CMV diagnosis during pregnancy of pregnant women. Methods Retrospectively, 1000 pregnant patients aged 17 to 45 years who were treated in the University Clinic St. Hedwig, Germany, were included in the study. It was investigated whether a CMV test was carried out during pregnancy and which results were obtained. Results 597 patients (59.7%) had not received a CMV test during pregnancy. Among the 403 (40.3%) patients who had undergone CMV testing, immunity was detected in 143 (35.5%). 257 patients (63.8%) showed no immunity, while 3 (0.74%) had an active infection. Conclusion Although CMV is the most common pathogen of viral congenital infections, which can severely impair the health of affected newborns, and both hyperimmune globulin administration as well as antiviral therapy now show good preventive and therapeutic success, CMV diagnostics during pregnancy is still not an integral part of the maternity guidelines in Germany, but rather an individualized healthcare service (IGeL). Unfortunately, there is currently no vaccination available to prevent vertical transmission, which is why early diagnosis and hygiene measures are the most important means of preventing seroconversion of the mother and possible infection of the fetus. cytomegalovirus prenatal care congenital infection pregnancy Figures Figure 1 Figure 2 What does this study add to the clinical work Even though CMV can severely impact the health of newborns, CMV testing is not offered as part of the standard prenatal care in Germany. Our study showed that the majority of the pregnant women in Germany do not undergo a CMV testing and most of those tested, show no immunity. INTRODUCTION Human Cytomegalovirus belongs to the family of herpes viruses and is the most common pathogen of viral congenital infection [ 1 ]. The prevalence depends on various factors e.g. socioeconomic status, hygiene, age, number of sexual partners, contact to toddlers [ 2 ]. Immunocompetent adults are usually asymptomatic in case of a primary CMV infection, whereas it can be dangerous for immunocompromised individuals [ 3 ]. CMV can be transmitted through contact with infected body fluids [ 4 ]. A vertical transmission can lead to a congenital infection. A maternal primary infection can lead to severe outcomes concerning fetus’ health [ 5 ]. The risk of transmission increases with gestational age, whereas the risk of fetal impairment decreases [ 6 , 7 ]. The severity of the symptoms in infected newborns is diverse including hepatosplenomegaly, thrombocytopenia, hemolytic anemia, microcephaly, chorioretinitis, intrauterine growth restriction, low birth weight, motor and cognitive disorders, visual impairment as well as sensorineural hearing loss (SNHL) [ 8 ]. The majority of infected newborns are asymptomatic at birth, yet some can develop late-onset-SNHL [ 9 ]. Early intervention in case of cCMV is crucial for the outcome, therefore early diagnosis during pregnancy can have a positive impact on the affected newborns [ 10 ]. Most pregnant women are not sufficiently informed about cCMV and the relevance of preventive measures [ 11 ]. Momentarily, there is no validated vaccine or treatment during pregnancy, that can prevent the vertical transmission, thus educating pregnant women about CMV and adhering to hygiene measures are currently the most important measures for preventing seroconversion during pregnancy [ 12 ]. Unfortunately, in Germany there is no antenatal screening program for CMV and CMV testing in the first trimester is offered upon patient request or after recommendation as part of an individual healthcare service (IGel), i.e. that the patients must carry the costs. Aim of our study is to evaluate the frequency of CMV testing during pregnancy as an individual healthcare service, since in Germany the available literature to the subject is limited. MATERIALS AND METHODS This retrospective, anonymized single center cohort study was performed from June 2021 until August 2022 at the Tertiary Maternity Clinic St. Hedwig of The Order of St. John, University Department of Obstetrics and Gynecology, University of Regensburg. Data of 1000 pregnant women, who were treated and delivered in our clinic, were collected from their medical records. The data analyzed, included maternal date of birth, age, gravity- and parity-status, CMV-immunity- status, due date, date and mode of delivery, gestational age at delivery and sex of the newborn. In cases of active infection, details about therapy and neonatal outcome were registered and reported. Data collection was performed using SAP® (© 2024 SAP SE), Viewpoint 6 (Generic Electric Company, Boston, USA) and the “Mutterpass”, a documentation booklet that is part of maternal care following the “Mutterschaftsrichtlinien” in Germany and saved anonymously in Microsoft Excel® for MacOS (Microsoft Corporation, 2022, Version 16.67), therefore an informed consent of the patients was not required. The statistical analysis was performed using GraphPad PRISM 10.2.3® (MacOS, GraphPad Software, San Diego, California, USA). A t-test was used to compare the means of normally distributed continuous values. The Mann-Whitney U-test was used to compare two non-normally distributed continuous groups. For contingency tables, Fisher's exact test was used. One-way Welch’s ANOVA was used to compare the means of more than two normally distributed groups with unequal standard deviations assumed. For post-hoc multiple comparisons Dunnett’s T3-test was used. A p-value of < 0.05 was considered statistically significant. RESULTS Patient characteristics 1000 pregnant women, aged between 17 to 45 (Mean: 32.29 years, SD = 4.76), were enrolled in the study. All newborns were live births (488 female, 535 males, 977 singletons, 23 twin births). Regarding the delivery mode, 599 gave birth spontaneously, 131 by planned and 187 by unplanned C-section. 82 were instrumental deliveries. In one twin birth, spontaneous delivery of the first child was followed by emergency C-section of the second child due to heavy bleeding of the mother, resulting in deterioration of the general condition and hemodynamic instability, implicating placental abruption (Fig. 1 A). Frequency of CMV testing CMV test was performed in 403 patients (40.3%). Among these, 143 (35.5%) showed immunity, 257 (63.8%) showed no immunity and three (0.75%) had an active infection (Fig. 1 B, 1 C). A subgroup of 15 patients was identified, who underwent the test in a previous pregnancy, i.e. during their second pregnancy, of which 13 were secundipara, one was para-3 and one para-4. 11 of 15 women showed immunity, while four did not. Premature birth rate In our set of data, 108 (10.8%) premature births were recorded. In 70 women (64.8%) no CMV test was conducted, while 38 (35.1%) were tested and 31 of them showed no immunity. In this subgroup, we analyzed whether the CMV-immunity status can affect the risk of premature birth. A statistically significant difference was found between the subgroups mentioned above: less women with immunity had a preterm birth compared to those without immunity (p = 0.02, OR = 0.375, 95% CI = 0.154–0.865) (Table 1 ). Table 1 Premature birth rate in relation to immunity status: a statistically significant difference was found between women with and without immunity in the premature birth group; more women without immunity had a preterm birth compared to those with immunity. Data Analyzed Preterm birth Full-term birth Total Immunity 7 136 143 No Immunity 31 226 257 Total 38 362 400 Gestational age at delivery The differences in the gestational age at delivery between the patients with or without immunity as well as those with an active CMV infection, were compared. No significant difference in gestational age between the groups was found (p = 0.27, Median: 40 vs. 40) (Table S1 ,S2). Age of pregnant women undergoing a CMV test The statistical analysis indicated that women undergoing a CMV test were on average older than the patients without (Mean: 32.94 vs. 31.85 years, p = 0.0004) (Fig. 2 B) (Table S3,S4). Comparing the three subgroups immunity vs. no immunity vs. active infection, no significant difference in age was revealed (Mean: 32.35 vs. 33.26 vs. 33.84 years, p = 0.29) (Fig. 2 C) (Table S5,S6). Active Infections In this study, three active CMV infections were recorded in patients, aged between 29–38 years. Two of them being secundipara and one primipara, had either a periconceptional CMV infection or an infection in the first trimester. A treatment with CMV-HIG (hyperimmune globulin), in a dosage of 200 IU/kg BW (body weight) i.v. (intravenous), was administered in all three patients biweekly, starting at 11 to 14 until 19 to 21 weeks. An amniocentesis was suggested to all of them in the second trimester. Patient A agreed to it, showing no signs of CMV in the amniotic fluid. The detailed fetal scan showed no abnormal findings at any of them. All three patients gave birth between 41–42 weeks. The CMV diagnostics performed on the newborns were negative for CMV infection. DISCUSSION In this study, we aimed to assess the frequency of CMV testing during pregnancy as an individual healthcare service. We evaluated the data of 1000 pregnant women that were treated and gave birth in our clinic, which is a highly representative local German cohort. According to our results, most of the patients did not receive any CMV testing (59.7%). Most of the tested patients, showed no CMV immunity (63.8%). The prevalence of an active infection (0.75%) turned out to be rather low. The data regarding the CMV seroprevalence is heterogenic. In industrialized countries is about 42.3%-68.3% among adults [ 13 ], with great regional differences existing [ 14 ]. In Germany the data available regarding the CMV seroprevalence among pregnant women is limited. Enders et al. described a seroprevalence among pregnant women of 42.3% [ 15 ]. Our results revealed an overall seroprevalence of 36.2%. Concerning the likelihood of a vertical transmission during primary compared to non-primary infection, most authors report a higher transmission rate in case of a primary infection. The transmission rate varies internationally enormously [ 16 – 18 ]. The prevalence of cCMV (congenital cytomegalovirus infection) at birth increases with increasing maternal CMV prevalence. A possible explanation is that with a high seroprevalence in the population, the risk of CMV reactivation/reinfection is greater, and this risk exceeds the protective effect of maternal CMV immunity regarding transplacentar transmission [ 4 , 19 , 20 ]. For example, the cCMV prevalence at birth in countries like Brazil is 1.1%, where the seroprevalence in the population is about 96%. Similarly high prevalence of cCMV can be found in Africa (0.9–1.4%) [ 21 ], China (1.8%) [ 22 ] and India (2.1%) [ 23 ], where the CMV seroprevalence is almost 100%. In contrary, the prevalence of cCMV fluctuates in Europe and the USA between 0.18–0.48% with a much lower CMV seroprevalence of about 30–40% [ 24 ]. Hygiene measures -especially for pregnant women with high occupational or familial CMV exposure- are the most important component of primary prevention of cCMV infection. Several studies have shown that by advising pregnant women about the significance of cCMV infection and the possible hygiene measures, especially during the first trimester, the risk of infection can be significantly minimized, thus contributing immensely to the prevention of infection [ 25 – 27 ]. In our patient population, it is unclear whether the patients were informed about the primary prevention measures by their gynecologist during maternal care. However, the study took place during the COVID-19 pandemic, so it can be assumed that during this time the entire population, including our study participants, were extensively informed about hygiene measures (keeping distance, hygiene, everyday masks) and followed them, which could influence our results and explain the lower CMV seroprevalence values (36.2%) compared to the literature data regarding pregnant women in Germany. In case of a CMV infection during pregnancy measures need to be taken to avoid vertical transmission. HIG treatment is an option of treatment, which has been controversially discussed. According to the prospective, randomized trial of Revello et al., HIG treatment cannot reduce the risk of transmission (30% HIG group vs. 44% placebo group; p = 0.13) [ 28 ]. However, this study has a few limitations that need to be considered, e.g. pregnant women with a CMV infection in the second trimester were also included, so the time between diagnosis and the first HIG treatment was in some cases longer than 5 weeks, the treatment took place once per month, whereas the half-life of HIG is 11 days, and the dose was 100 IU/kg BW [ 6 ]. In contrary Kagan et al., showed the efficacy of HIG treatment and that the risk of materno-fetal transmission can be significantly reduced (7.5% vs. 35.2%; p < 0.0001). In this study, the patients included were selected using strict criteria: primary CMV infection at or prior to 14 weeks, high IgM (Immunoglobulin M) index, low IgG (Immunoglobulin G) levels, low IgG avidity, absence of gB2 (Glycoprotein B genotype 2) reactivity. HIG was administered in a dose of 200 IU/kg maternal BW and was repeated biweekly until 20 weeks [ 29 ]. In our study three patients with an active CMV infection were detected. HIG administration was performed “off-label" biweekly starting before or at 14 weeks in a dose of 200 IU/ kg BW. The three newborns were tested for CMV infection postnatally and were all negative. However, due to the limited number of patients in our study with an active infection, it is not possible to make significant conclusions regarding the efficacy of HIG treatment. According to a RCT (randomized controlled trial) in 2020 and following quasi-randomized trials, through administration of oral 8g/day valaciclovir, a reduction of 70% in the vertical transmission rate in case of a maternal primary infection acquired periconceptionally or during the first trimester, can be achieved, if initiated as soon as possible [ 30 ]. In case of a vertical transmission the aim is to reduce the severity of the effects on the fetus. The mother can be treated with 8g valaciclovir per day until the end of the pregnancy. Lereuz-Ville et al. have evaluated the efficacy of antiviral treatment with valaciclovir and demonstrated that high-dosage valaciclovir is effective in improving the outcome of moderately symptomatic fetuses [ 30 ]. None of our three patients with an active CMV infection needed to be treated with valaciclovir. An amniocentesis was performed at one of them at 21 weeks and the amniotic fluid was negative for CMV, so that a treatment with valaciclovir was not necessary. The other two patients rejected an amniocentesis, but the ultrasound scan performed showed no signs of CMV infection. Moreover, 108 premature births were recorded. Most of these women did not undergo a CMV screening (64.8%, n = 70). Considering the ones that were tested for CMV during pregnancy (35.1%, n = 38), 31 (12.07%) showed no immunity. Looking at the total patient population (n = 1000), no significant difference regarding the gestational age at birth between those with and without immunity could be observed (p = 0.27). A possible explanation for the latter results is that women with no immunity are more susceptible to a primary CMV infection. CMV can influence the development and function of placenta through various immunological pathways leading to an increased risk of intrauterine growth restriction, premature birth and still birth [ 31 ]. Premature delivery is associated with lower socioeconomic status [ 32 , 33 ]. There may be a co-incidence of several risk factors for preterm birth and a higher probability to miss CMV testing. Since CMV testing in Germany is optional and cost-intensive for the individual, this aspect may mainly contribute to our findings that women with preterm birth are at higher risk not to be tested. Our study showed that, pregnant women with a CMV test were significantly older than those without, with a mean age of 32.94 years. In this case, it can be assumed, that the older the pregnant woman is, the more likely it is, that the pregnancy was planned, and that more individual health services are used. In addition, older patients may already have small children who represent a CMV reservoir. Accordingly, a CMV test was carried out on these patients with an increased risk of CMV exposure as part of primary prevention. Among the subgroups of patients, who were tested (immunity, no immunity, active infection), no significant age difference was observed. Although CMV is the most common cause of viral congenital infections and can strongly impact the health of affected newborns, in Germany there is no antenatal screening program. Data collected from other European countries, e.g. Austria, Italy, Greece, Belgium, and certain regions of France, where CMV testing is part of routine screening, have contributed to better research and understanding of the pathophysiology of congenital CMV, CMV diagnostics, and the importance of hygiene as a preventive measure [34–37]. To date, despite extensive research, neither a vaccine nor an approved therapy is available. However, the administration of HIG and antiviral therapy (“off-label”) have shown good preventive and therapeutic outcomes. Therefore, early diagnosis and hygiene measures remain the most important means for preventing maternal seroconversion and consequently, a potential vertical infection of the fetus. CONCLUSION Although CMV can severely impair the health of affected newborns in case of congenital infection, CMV diagnostics during pregnancy is still an individualized health service. Under current conditions, more than half of pregnant women in Germany do not undergo CMV testing. Unfortunately, there is currently no vaccination available to prevent vertical transmission, which is why early diagnosis and hygiene measures are the most important means of preventing seroconversion of the mother and possible infection of the fetus. Our results strongly indicate the importance of a general CMV screening available to all pregnant women in Germany. Declarations Funding No funds, grants, or other support was received. Competing Interests The authors have no relevant financial or non-financial interests to disclose. Ethics approval Ethical approval was waived by the local Ethics Committee of University of Regensburg in view of the retrospective nature of the study and all the procedures being performed were part of the routine care (24-3826-104). Consent to participate Data collected retrospectively was saved anonymously, therefore an informed consent of the patients was not required. Author Contributions A Hadjiiona: Data collection and management, data analysis, manuscript writing and editing Data curation, interpretation of data; I Michaelides: Data analysis, manuscript editing writing-review and editing; P Kummer: Manuscript editing, Writing-review and editing, interpretation of data; M Kappelmeyer: Manuscript editing, writing-review and editing ; A Koeninger: Project development, manuscript editing , writing-review and editing, project administration, supervision, validation; E Reuschel: Project development, data analysis, manuscript editing, writing-review and editing, project administration, supervision, validation All authors read and approved the final manuscript. References Marsico C, Kimberlin DW: Congenital Cytomegalovirus infection: advances and challenges in diagnosis, prevention and treatment. 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Cite Share Download PDF Status: Published Journal Publication published 31 Jan, 2025 Read the published version in Archives of Gynecology and Obstetrics → Version 1 posted Reviewers agreed at journal 10 Oct, 2024 Reviewers invited by journal 10 Oct, 2024 Editor invited by journal 10 Oct, 2024 Editor assigned by journal 10 Oct, 2024 First submitted to journal 08 Oct, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5227922","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":364585284,"identity":"3b58d1d5-bd55-4148-b094-6d5fa84414e8","order_by":0,"name":"Antigoni Hadjiiona","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABAElEQVRIiWNgGAWjYJCCA0DMwyDBwCAhUQFkMjM3ENDAjKzlDEiAkbAWCABpYWwDsQho4Z/df/Dgl4o7MgzSzQ9vWM6rjeZvB2r5UbENpxaJO4cZDsucecbDIHPM2EJy2/HcGYcZGxh7ztzGbc2NZIbDkm2HgX5JMJOQ3HYstwGohZmxDbcWeYSW9G8SknOO5c4npMUAqOXgR7CWHKAtDTW5GwhpMbyRbHCY4cxhHjaJnGILiWMHcjcCtRzE5xe5G4mPP/6oOGzPL5G+8bZETV3uvPOHDz74UYHH+0DAzAMk2EAMCYbDYJEDeNUDAeMPGOMDQx0hxaNgFIyCUTACAQCQZlsfwwQtAAAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0009-0002-9434-5060","institution":"","correspondingAuthor":true,"prefix":"","firstName":"Antigoni","middleName":"","lastName":"Hadjiiona","suffix":""},{"id":364585285,"identity":"6652e28f-1d0a-49c0-bd49-f73d126b975b","order_by":1,"name":"Ioannis Michaelides","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Ioannis","middleName":"","lastName":"Michaelides","suffix":""},{"id":364585286,"identity":"e3d57dd3-a3f2-4df2-aef6-55c5e90780b9","order_by":2,"name":"Peter Kummer","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Peter","middleName":"","lastName":"Kummer","suffix":""},{"id":364585287,"identity":"c0f4129e-5d14-4fde-9e00-7a69e2133c06","order_by":3,"name":"Maurice Kappelmeyer","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Maurice","middleName":"","lastName":"Kappelmeyer","suffix":""},{"id":364585288,"identity":"3a368f93-429e-40c6-a210-2383f6832ae7","order_by":4,"name":"Angela Koeninger","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Angela","middleName":"","lastName":"Koeninger","suffix":""},{"id":364585289,"identity":"c27b8522-3977-4cd5-aead-9b9e496ac398","order_by":5,"name":"Edith Reuschel","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Edith","middleName":"","lastName":"Reuschel","suffix":""}],"badges":[],"createdAt":"2024-10-08 21:19:45","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5227922/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5227922/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00404-025-07962-3","type":"published","date":"2025-01-31T15:57:34+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":67202547,"identity":"ee4701f3-c402-4044-b75f-49cd61189305","added_by":"auto","created_at":"2024-10-22 10:18:41","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":266286,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eA: Overview of birth mode, B: Immunity status, C: CMV testing (SD-spontaneous delivery, PCS-primary C-section, SCS-secondary C-section, ID-instrumental delivery).\u003c/em\u003e\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-5227922/v1/e85738186d96e6089fa821a6.png"},{"id":67202548,"identity":"642d9449-4396-4276-9cfe-7d37ad586f79","added_by":"auto","created_at":"2024-10-22 10:18:41","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":316456,"visible":true,"origin":"","legend":"\u003cp\u003eCMV testing related to age and status of immunity. A: Overall collective, B: Women tested were on average older than the patients without a test, C: No significant difference was revealed between the three subgroups of patients receiving test.\u003c/p\u003e","description":"","filename":"floatimage240.png","url":"https://assets-eu.researchsquare.com/files/rs-5227922/v1/6258a8b9ff3fcc9a9d8a088f.png"},{"id":75351285,"identity":"5e205bee-5be8-4298-8214-e4b5a0a24a95","added_by":"auto","created_at":"2025-02-03 16:08:57","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":925658,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5227922/v1/a6688f5a-a101-44bc-ba1b-401d4d05b034.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eFrequeny of CMV Testing During Pregnancy- A Retrospective Study\u003c/p\u003e","fulltext":[{"header":"What does this study add to the clinical work","content":"\u003cp\u003eEven though CMV can severely impact the health of newborns, CMV testing is not offered as part of the standard prenatal care in Germany. Our study showed that the majority of the pregnant women in Germany do not undergo a CMV testing and most of those tested, show no immunity.\u003c/p\u003e"},{"header":"INTRODUCTION","content":"\u003cp\u003eHuman Cytomegalovirus belongs to the family of herpes viruses and is the most common pathogen of viral congenital infection [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The prevalence depends on various factors e.g. socioeconomic status, hygiene, age, number of sexual partners, contact to toddlers [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Immunocompetent adults are usually asymptomatic in case of a primary CMV infection, whereas it can be dangerous for immunocompromised individuals [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCMV can be transmitted through contact with infected body fluids [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. A vertical transmission can lead to a congenital infection. A maternal primary infection can lead to severe outcomes concerning fetus\u0026rsquo; health [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The risk of transmission increases with gestational age, whereas the risk of fetal impairment decreases [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. The severity of the symptoms in infected newborns is diverse including hepatosplenomegaly, thrombocytopenia, hemolytic anemia, microcephaly, chorioretinitis, intrauterine growth restriction, low birth weight, motor and cognitive disorders, visual impairment as well as sensorineural hearing loss (SNHL) [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The majority of infected newborns are asymptomatic at birth, yet some can develop late-onset-SNHL [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eEarly intervention in case of cCMV is crucial for the outcome, therefore early diagnosis during pregnancy can have a positive impact on the affected newborns [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Most pregnant women are not sufficiently informed about cCMV and the relevance of preventive measures [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Momentarily, there is no validated vaccine or treatment during pregnancy, that can prevent the vertical transmission, thus educating pregnant women about CMV and adhering to hygiene measures are currently the most important measures for preventing seroconversion during pregnancy [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Unfortunately, in Germany there is no antenatal screening program for CMV and CMV testing in the first trimester is offered upon patient request or after recommendation as part of an individual healthcare service (IGel), i.e. that the patients must carry the costs.\u003c/p\u003e \u003cp\u003eAim of our study is to evaluate the frequency of CMV testing during pregnancy as an individual healthcare service, since in Germany the available literature to the subject is limited.\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cp\u003eThis retrospective, anonymized single center cohort study was performed from June 2021 until August 2022 at the Tertiary Maternity Clinic St. Hedwig of The Order of St. John, University Department of Obstetrics and Gynecology, University of Regensburg. Data of 1000 pregnant women, who were treated and delivered in our clinic, were collected from their medical records. The data analyzed, included maternal date of birth, age, gravity- and parity-status, CMV-immunity- status, due date, date and mode of delivery, gestational age at delivery and sex of the newborn. In cases of active infection, details about therapy and neonatal outcome were registered and reported.\u003c/p\u003e \u003cp\u003eData collection was performed using SAP\u0026reg; (\u0026copy; 2024 SAP SE), Viewpoint 6 (Generic Electric Company, Boston, USA) and the \u0026ldquo;Mutterpass\u0026rdquo;, a documentation booklet that is part of maternal care following the \u0026ldquo;Mutterschaftsrichtlinien\u0026rdquo; in Germany and saved anonymously in Microsoft Excel\u0026reg; for MacOS (Microsoft Corporation, 2022, Version 16.67), therefore an informed consent of the patients was not required. The statistical analysis was performed using GraphPad PRISM 10.2.3\u0026reg; (MacOS, GraphPad Software, San Diego, California, USA). A t-test was used to compare the means of normally distributed continuous values. The Mann-Whitney U-test was used to compare two non-normally distributed continuous groups. For contingency tables, Fisher's exact test was used. One-way Welch\u0026rsquo;s ANOVA was used to compare the means of more than two normally distributed groups with unequal standard deviations assumed. For post-hoc multiple comparisons Dunnett\u0026rsquo;s T3-test was used. A p-value of \u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003ePatient characteristics\u003c/h2\u003e \u003cp\u003e1000 pregnant women, aged between 17 to 45 (Mean: 32.29 years, SD\u0026thinsp;=\u0026thinsp;4.76), were enrolled in the study. All newborns were live births (488 female, 535 males, 977 singletons, 23 twin births). Regarding the delivery mode, 599 gave birth spontaneously, 131 by planned and 187 by unplanned C-section. 82 were instrumental deliveries. In one twin birth, spontaneous delivery of the first child was followed by emergency C-section of the second child due to heavy bleeding of the mother, resulting in deterioration of the general condition and hemodynamic instability, implicating placental abruption (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eFrequency of CMV testing\u003c/h3\u003e\n\u003cp\u003eCMV test was performed in 403 patients (40.3%). Among these, 143 (35.5%) showed immunity, 257 (63.8%) showed no immunity and three (0.75%) had an active infection (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB,\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC).\u003c/p\u003e \u003cp\u003eA subgroup of 15 patients was identified, who underwent the test in a previous pregnancy, i.e. during their second pregnancy, of which 13 were secundipara, one was para-3 and one para-4. 11 of 15 women showed immunity, while four did not.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003ePremature birth rate\u003c/h3\u003e\n\u003cp\u003eIn our set of data, 108 (10.8%) premature births were recorded. In 70 women (64.8%) no CMV test was conducted, while 38 (35.1%) were tested and 31 of them showed no immunity.\u003c/p\u003e \u003cp\u003eIn this subgroup, we analyzed whether the CMV-immunity status can affect the risk of premature birth. A statistically significant difference was found between the subgroups mentioned above: less women with immunity had a preterm birth compared to those without immunity (p\u0026thinsp;=\u0026thinsp;0.02, OR\u0026thinsp;=\u0026thinsp;0.375, 95% CI\u0026thinsp;=\u0026thinsp;0.154\u0026ndash;0.865) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePremature birth rate in relation to immunity status: a statistically significant difference was found between women with and without immunity in the premature birth group; more women without immunity had a preterm birth compared to those with immunity.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eData Analyzed\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePreterm birth\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFull-term birth\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eImmunity\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e136\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e143\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNo Immunity\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e226\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e257\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTotal\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e362\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e400\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\n\u003ch3\u003eGestational age at delivery\u003c/h3\u003e\n\u003cp\u003eThe differences in the gestational age at delivery between the patients with or without immunity as well as those with an active CMV infection, were compared. No significant difference in gestational age between the groups was found (p\u0026thinsp;=\u0026thinsp;0.27, Median: 40 vs. 40) (Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e,S2).\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eAge of pregnant women undergoing a CMV test\u003c/h2\u003e \u003cp\u003eThe statistical analysis indicated that women undergoing a CMV test were on average older than the patients without (Mean: 32.94 vs. 31.85 years, p\u0026thinsp;=\u0026thinsp;0.0004) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB) (Table S3,S4).\u003c/p\u003e \u003cp\u003eComparing the three subgroups immunity vs. no immunity vs. active infection, no significant difference in age was revealed (Mean: 32.35 vs. 33.26 vs. 33.84 years, p\u0026thinsp;=\u0026thinsp;0.29) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC) (Table S5,S6).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eActive Infections\u003c/h3\u003e\n\u003cp\u003eIn this study, three active CMV infections were recorded in patients, aged between 29\u0026ndash;38 years. Two of them being secundipara and one primipara, had either a periconceptional CMV infection or an infection in the first trimester. A treatment with CMV-HIG (hyperimmune globulin), in a dosage of 200 IU/kg BW (body weight) i.v. (intravenous), was administered in all three patients biweekly, starting at 11 to 14 until 19 to 21 weeks. An amniocentesis was suggested to all of them in the second trimester. Patient A agreed to it, showing no signs of CMV in the amniotic fluid. The detailed fetal scan showed no abnormal findings at any of them. All three patients gave birth between 41\u0026ndash;42 weeks. The CMV diagnostics performed on the newborns were negative for CMV infection.\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eIn this study, we aimed to assess the frequency of CMV testing during pregnancy as an individual healthcare service. We evaluated the data of 1000 pregnant women that were treated and gave birth in our clinic, which is a highly representative local German cohort.\u003c/p\u003e \u003cp\u003eAccording to our results, most of the patients did not receive any CMV testing (59.7%). Most of the tested patients, showed no CMV immunity (63.8%). The prevalence of an active infection (0.75%) turned out to be rather low.\u003c/p\u003e \u003cp\u003eThe data regarding the CMV seroprevalence is heterogenic. In industrialized countries is about 42.3%-68.3% among adults [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], with great regional differences existing [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. In Germany the data available regarding the CMV seroprevalence among pregnant women is limited. Enders et al. described a seroprevalence among pregnant women of 42.3% [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Our results revealed an overall seroprevalence of 36.2%.\u003c/p\u003e \u003cp\u003eConcerning the likelihood of a vertical transmission during primary compared to non-primary infection, most authors report a higher transmission rate in case of a primary infection. The transmission rate varies internationally enormously [\u003cspan additionalcitationids=\"CR17\" citationid=\"CR17\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. The prevalence of cCMV (congenital cytomegalovirus infection) at birth increases with increasing maternal CMV prevalence. A possible explanation is that with a high seroprevalence in the population, the risk of CMV reactivation/reinfection is greater, and this risk exceeds the protective effect of maternal CMV immunity regarding transplacentar transmission [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. For example, the cCMV prevalence at birth in countries like Brazil is 1.1%, where the seroprevalence in the population is about 96%. Similarly high prevalence of cCMV can be found in Africa (0.9\u0026ndash;1.4%) [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e21\u003c/span\u003e], China (1.8%) [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e22\u003c/span\u003e] and India (2.1%) [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e23\u003c/span\u003e], where the CMV seroprevalence is almost 100%. In contrary, the prevalence of cCMV fluctuates in Europe and the USA between 0.18\u0026ndash;0.48% with a much lower CMV seroprevalence of about 30\u0026ndash;40% [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHygiene measures -especially for pregnant women with high occupational or familial CMV exposure- are the most important component of primary prevention of cCMV infection. Several studies have shown that by advising pregnant women about the significance of cCMV infection and the possible hygiene measures, especially during the first trimester, the risk of infection can be significantly minimized, thus contributing immensely to the prevention of infection [\u003cspan additionalcitationids=\"CR26\" citationid=\"CR26\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. In our patient population, it is unclear whether the patients were informed about the primary prevention measures by their gynecologist during maternal care. However, the study took place during the COVID-19 pandemic, so it can be assumed that during this time the entire population, including our study participants, were extensively informed about hygiene measures (keeping distance, hygiene, everyday masks) and followed them, which could influence our results and explain the lower CMV seroprevalence values (36.2%) compared to the literature data regarding pregnant women in Germany.\u003c/p\u003e \u003cp\u003eIn case of a CMV infection during pregnancy measures need to be taken to avoid vertical transmission. HIG treatment is an option of treatment, which has been controversially discussed. According to the prospective, randomized trial of Revello et al., HIG treatment cannot reduce the risk of transmission (30% HIG group vs. 44% placebo group; p\u0026thinsp;=\u0026thinsp;0.13) [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. However, this study has a few limitations that need to be considered, e.g. pregnant women with a CMV infection in the second trimester were also included, so the time between diagnosis and the first HIG treatment was in some cases longer than 5 weeks, the treatment took place once per month, whereas the half-life of HIG is 11 days, and the dose was 100 IU/kg BW [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn contrary Kagan et al., showed the efficacy of HIG treatment and that the risk of materno-fetal transmission can be significantly reduced (7.5% vs. 35.2%; p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). In this study, the patients included were selected using strict criteria: primary CMV infection at or prior to 14 weeks, high IgM (Immunoglobulin M) index, low IgG (Immunoglobulin G) levels, low IgG avidity, absence of gB2 (Glycoprotein B genotype 2) reactivity. HIG was administered in a dose of 200 IU/kg maternal BW and was repeated biweekly until 20 weeks [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e29\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn our study three patients with an active CMV infection were detected. HIG administration was performed \u0026ldquo;off-label\" biweekly starting before or at 14 weeks in a dose of 200 IU/ kg BW. The three newborns were tested for CMV infection postnatally and were all negative. However, due to the limited number of patients in our study with an active infection, it is not possible to make significant conclusions regarding the efficacy of HIG treatment.\u003c/p\u003e \u003cp\u003eAccording to a RCT (randomized controlled trial) in 2020 and following quasi-randomized trials, through administration of oral 8g/day valaciclovir, a reduction of 70% in the vertical transmission rate in case of a maternal primary infection acquired periconceptionally or during the first trimester, can be achieved, if initiated as soon as possible [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e30\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn case of a vertical transmission the aim is to reduce the severity of the effects on the fetus. The mother can be treated with 8g valaciclovir per day until the end of the pregnancy. Lereuz-Ville et al. have evaluated the efficacy of antiviral treatment with valaciclovir and demonstrated that high-dosage valaciclovir is effective in improving the outcome of moderately symptomatic fetuses [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. None of our three patients with an active CMV infection needed to be treated with valaciclovir. An amniocentesis was performed at one of them at 21 weeks and the amniotic fluid was negative for CMV, so that a treatment with valaciclovir was not necessary. The other two patients rejected an amniocentesis, but the ultrasound scan performed showed no signs of CMV infection.\u003c/p\u003e \u003cp\u003eMoreover, 108 premature births were recorded. Most of these women did not undergo a CMV screening (64.8%, n\u0026thinsp;=\u0026thinsp;70). Considering the ones that were tested for CMV during pregnancy (35.1%, n\u0026thinsp;=\u0026thinsp;38), 31 (12.07%) showed no immunity. Looking at the total patient population (n\u0026thinsp;=\u0026thinsp;1000), no significant difference regarding the gestational age at birth between those with and without immunity could be observed (p\u0026thinsp;=\u0026thinsp;0.27).\u003c/p\u003e \u003cp\u003eA possible explanation for the latter results is that women with no immunity are more susceptible to a primary CMV infection. CMV can influence the development and function of placenta through various immunological pathways leading to an increased risk of intrauterine growth restriction, premature birth and still birth [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Premature delivery is associated with lower socioeconomic status [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. There may be a co-incidence of several risk factors for preterm birth and a higher probability to miss CMV testing. Since CMV testing in Germany is optional and cost-intensive for the individual, this aspect may mainly contribute to our findings that women with preterm birth are at higher risk not to be tested.\u003c/p\u003e \u003cp\u003eOur study showed that, pregnant women with a CMV test were significantly older than those without, with a mean age of 32.94 years. In this case, it can be assumed, that the older the pregnant woman is, the more likely it is, that the pregnancy was planned, and that more individual health services are used. In addition, older patients may already have small children who represent a CMV reservoir. Accordingly, a CMV test was carried out on these patients with an increased risk of CMV exposure as part of primary prevention. Among the subgroups of patients, who were tested (immunity, no immunity, active infection), no significant age difference was observed.\u003c/p\u003e \u003cp\u003eAlthough CMV is the most common cause of viral congenital infections and can strongly impact the health of affected newborns, in Germany there is no antenatal screening program. Data collected from other European countries, e.g. Austria, Italy, Greece, Belgium, and certain regions of France, where CMV testing is part of routine screening, have contributed to better research and understanding of the pathophysiology of congenital CMV, CMV diagnostics, and the importance of hygiene as a preventive measure [34\u0026ndash;37].\u003c/p\u003e \u003cp\u003eTo date, despite extensive research, neither a vaccine nor an approved therapy is available. However, the administration of HIG and antiviral therapy (\u0026ldquo;off-label\u0026rdquo;) have shown good preventive and therapeutic outcomes. Therefore, early diagnosis and hygiene measures remain the most important means for preventing maternal seroconversion and consequently, a potential vertical infection of the fetus.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eAlthough CMV can severely impair the health of affected newborns in case of congenital infection, CMV diagnostics during pregnancy is still an individualized health service. Under current conditions, more than half of pregnant women in Germany do not undergo CMV testing. Unfortunately, there is currently no vaccination available to prevent vertical transmission, which is why early diagnosis and hygiene measures are the most important means of preventing seroconversion of the mother and possible infection of the fetus. Our results strongly indicate the importance of a general CMV screening available to all pregnant women in Germany.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funds, grants, or other support was received.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthical approval was waived by the local Ethics Committee of University of Regensburg in view of the retrospective nature of the study and all the procedures being performed were part of the routine care (24-3826-104).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData collected retrospectively was\u0026nbsp;saved anonymously, therefore an informed consent of the patients was not required.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eA Hadjiiona:\u003c/strong\u003e Data collection and management, data analysis, manuscript writing and editing Data curation, interpretation of data; \u003cstrong\u003eI\u003c/strong\u003e \u003cstrong\u003eMichaelides:\u0026nbsp;\u003c/strong\u003eData analysis, manuscript editing writing-review and editing; \u003cstrong\u003eP\u003c/strong\u003e \u003cstrong\u003eKummer:\u003c/strong\u003e Manuscript editing, Writing-review and editing, interpretation of data; \u003cstrong\u003eM\u003c/strong\u003e \u003cstrong\u003eKappelmeyer:\u0026nbsp;\u003c/strong\u003eManuscript editing,\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003ewriting-review and editing\u003cstrong\u003e; A Koeninger:\u0026nbsp;\u003c/strong\u003eProject development, manuscript editing\u003cstrong\u003e,\u0026nbsp;\u003c/strong\u003ewriting-review and editing, project administration, supervision, validation; \u003cstrong\u003eE\u003c/strong\u003e \u003cstrong\u003eReuschel:\u003c/strong\u003e Project development, data analysis, manuscript editing, writing-review and editing, project administration, supervision, validation\u003c/p\u003e\n\u003cp\u003eAll authors read and approved the final manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMarsico C, Kimberlin DW: Congenital Cytomegalovirus infection: advances and challenges in diagnosis, prevention and treatment. Italian Journal of Pediatrics 2017;43(1).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKuessel L, Husslein H, Marschalek J, et al.: Prediction of Maternal Cytomegalovirus Serostatus in Early Pregnancy: A Retrospective Analysis in Western Europe. PLOS ONE 2015;10(12): e0145470.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLachmann R, Loenenbach A, Waterboer T, et al.: Cytomegalovirus (CMV) seroprevalence in the adult population of Germany. PLOS ONE 2018;13(7): e0200267.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKenneson A, Cannon MJ: Review and meta-analysis of the epidemiology of congenital cytomegalovirus (CMV) infection. Rev Med Virol 2007;17(4): 253\u0026ndash;276.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDavis NL, King CC, Kourtis AP: Cytomegalovirus infection in pregnancy. 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International Journal of Environmental Research and Public Health 2015;12(12): 15285\u0026ndash;15297.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchaefer MR, Holttum J, Olson M, et al.: \u0026lt;p\u0026gt;\u0026thinsp;Development and Assessment of a Prenatal Cytomegalovirus (CMV) Educational Survey: Implementation and Impact in a Metropolitan University-Based Clinic\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e. International Journal of Women's Health 2020;Volume 12: 1205\u0026ndash;1214.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang S, Hu L, Chen J, Xu B, Zhou Y-H, Hu Y: Cytomegalovirus Seroprevalence in Pregnant Women and Association with Adverse Pregnancy/Neonatal Outcomes in Jiangsu Province, China. PLoS ONE 2014;9(9): e107645.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBuxmann H, Hamprecht K, Meyer-Wittkopf M, Friese K: Primary Human Cytomegalovirus (HCMV) Infection in Pregnancy. Dtsch Arztebl Int 2017;114(4): 45\u0026ndash;52.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEnders G, Daiminger A, Lindemann L, et al.: Cytomegalovirus (CMV) seroprevalence in pregnant women, bone marrow donors and adolescents in Germany, 1996\u0026ndash;2010. Medical Microbiology and Immunology 2012;201(3): 303\u0026ndash;309.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePass RF, Arav-Boger R: Maternal and fetal cytomegalovirus infection: diagnosis, management, and prevention. F1000Research 2018;7: 255.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePass RF, Anderson B: Mother-to-Child Transmission of Cytomegalovirus and Prevention of Congenital Infection. J Pediatric Infect Dis Soc 2014;3 Suppl 1(Suppl 1): S2-6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFowler KB, Stagno S, Pass RF: Maternal immunity and prevention of congenital cytomegalovirus infection. Jama 2003;289(8): 1008\u0026ndash;1011.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAntona D, Lepoutre A, Fonteneau L, et al.: Seroprevalence of cytomegalovirus infection in France in 2010. Epidemiology and Infection 2017;145(7): 1471\u0026ndash;1478.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMussi-Pinhata MM, Yamamoto AY, Moura Brito RM, et al.: Birth prevalence and natural history of congenital cytomegalovirus infection in a highly seroimmune population. Clin Infect Dis 2009;49(4): 522\u0026ndash;528.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evan der Sande MA, Kaye S, Miles DJ, et al.: Risk factors for and clinical outcome of congenital cytomegalovirus infection in a peri-urban West-African birth cohort. PLoS One 2007;2(6): e492.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTsai CH, Tsai FJ, Shih YT, Wu SF, Liu SC, Tseng YH: Detection of congenital cytomegalovirus infection in Chinese newborn infants using polymerase chain reaction. Acta Paediatr 1996;85(10): 1241\u0026ndash;1243.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDar L, Pati SK, Patro AR, et al.: Congenital cytomegalovirus infection in a highly seropositive semi-urban population in India. Pediatr Infect Dis J 2008;27(9): 841\u0026ndash;843.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCannon MJ, Schmid DS, Hyde TB: Review of cytomegalovirus seroprevalence and demographic characteristics associated with infection. Rev Med Virol 2010;20(4): 202\u0026ndash;213.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRawlinson WD, Boppana SB, Fowler KB, et al.: Congenital cytomegalovirus infection in pregnancy and the neonate: consensus recommendations for prevention, diagnosis, and therapy. Lancet Infect Dis 2017;17(6): e177-e188.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAdler SP: Prevention of Maternal-Fetal Transmission of Cytomegalovirus. EBioMedicine 2015;2(9): 1027\u0026ndash;1028.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRevello MG, Tibaldi C, Masuelli G, et al.: Prevention of Primary Cytomegalovirus Infection in Pregnancy. EBioMedicine 2015;2(9): 1205\u0026ndash;1210.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRevello MG, Lazzarotto T, Guerra B, et al.: A randomized trial of hyperimmune globulin to prevent congenital cytomegalovirus. N Engl J Med 2014;370(14): 1316\u0026ndash;1326.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKagan KO, Enders M, Schampera MS, et al.: Prevention of maternal-fetal transmission of cytomegalovirus after primary maternal infection in the first trimester by biweekly hyperimmunoglobulin administration. Ultrasound Obstet Gynecol 2019;53(3): 383\u0026ndash;389.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLeruez-Ville M, Ghout I, Bussi\u0026egrave;res L, et al.: In utero treatment of congenital cytomegalovirus infection with valacyclovir in a multicenter, open-label, phase II study. American Journal of Obstetrics and Gynecology 2016;215(4): 462.e461-462.e410.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNjue A, Coyne C, Margulis AV, et al.: The Role of Congenital Cytomegalovirus Infection in Adverse Birth Outcomes: A Review of the Potential Mechanisms. Viruses 2020;13(1).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSlattery MM, Morrison JJ: Preterm delivery. Lancet 2002;360(9344): 1489\u0026ndash;1497.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKoullali B, Oudijk MA, Nijman TA, Mol BW, Pajkrt E: Risk assessment and management to prevent preterm birth. Semin Fetal Neonatal Med 2016;21(2): 80\u0026ndash;88.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAdler SP: Screening for cytomegalovirus during pregnancy. Infect Dis Obstet Gynecol 2011;2011: 1\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePuccio G, Cajozzo C, Canduscio LA, et al.: Epidemiology of Toxoplasma and CMV serology and of GBS colonization in pregnancy and neonatal outcome in a Sicilian population. Italian Journal of Pediatrics 2014;40(1): 23.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMargioula-Siarkou C, Kalogiannidis I, Petousis S, et al.: Cytomegalovirus, Toxoplasma gondii and Rubella Vertical Transmission Rates According to Mid-trimester Amniocentesis: A Retrospective Study. Int J Prev Med 2015;6: 32.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"archives-of-gynecology-and-obstetrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"arch","sideBox":"Learn more about [Archives of Gynecology and Obstetrics](https://www.springer.com/journal/404)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/arch/default.aspx","title":"Archives of Gynecology and Obstetrics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"cytomegalovirus, prenatal care, congenital infection, pregnancy","lastPublishedDoi":"10.21203/rs.3.rs-5227922/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5227922/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eThe cytomegalovirus (CMV) belongs to the family of human Herpesviridae and is distributed worldwide. It is the most common cause of viral congenital infections and can have serious consequences for the health of the fetus in the event of a vertical infection. The aim of this study is to evaluate the frequency of CMV diagnosis during pregnancy of pregnant women.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eRetrospectively, 1000 pregnant patients aged 17 to 45 years who were treated in the University Clinic St. Hedwig, Germany, were included in the study. It was investigated whether a CMV test was carried out during pregnancy and which results were obtained.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003e597 patients (59.7%) had not received a CMV test during pregnancy. Among the 403 (40.3%) patients who had undergone CMV testing, immunity was detected in 143 (35.5%). 257 patients (63.8%) showed no immunity, while 3 (0.74%) had an active infection.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003e Although CMV is the most common pathogen of viral congenital infections, which can severely impair the health of affected newborns, and both hyperimmune globulin administration as well as antiviral therapy now show good preventive and therapeutic success, CMV diagnostics during pregnancy is still not an integral part of the maternity guidelines in Germany, but rather an individualized healthcare service (IGeL). Unfortunately, there is currently no vaccination available to prevent vertical transmission, which is why early diagnosis and hygiene measures are the most important means of preventing seroconversion of the mother and possible infection of the fetus.\u003c/p\u003e","manuscriptTitle":"Frequeny of CMV Testing During Pregnancy- A Retrospective Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-22 10:18:36","doi":"10.21203/rs.3.rs-5227922/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2024-10-10T16:06:42+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-10-10T13:31:29+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"Archives of Gynecology and Obstetrics","date":"2024-10-10T10:18:20+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-10-10T08:04:41+00:00","index":"","fulltext":""},{"type":"submitted","content":"Archives of Gynecology and Obstetrics","date":"2024-10-08T17:19:27+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"archives-of-gynecology-and-obstetrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"arch","sideBox":"Learn more about [Archives of Gynecology and Obstetrics](https://www.springer.com/journal/404)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/arch/default.aspx","title":"Archives of Gynecology and Obstetrics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"7c8beaa5-b041-443a-a5bf-750e4e9e6d87","owner":[],"postedDate":"October 22nd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-02-03T16:02:31+00:00","versionOfRecord":{"articleIdentity":"rs-5227922","link":"https://doi.org/10.1007/s00404-025-07962-3","journal":{"identity":"archives-of-gynecology-and-obstetrics","isVorOnly":false,"title":"Archives of Gynecology and Obstetrics"},"publishedOn":"2025-01-31 15:57:34","publishedOnDateReadable":"January 31st, 2025"},"versionCreatedAt":"2024-10-22 10:18:36","video":"","vorDoi":"10.1007/s00404-025-07962-3","vorDoiUrl":"https://doi.org/10.1007/s00404-025-07962-3","workflowStages":[]},"version":"v1","identity":"rs-5227922","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5227922","identity":"rs-5227922","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}