{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T15:49:37Z","timestamp":1791992977080,"version":"4.4.0"},"reference-count":31,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T00:00:00Z","timestamp":1680480000000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ultrasound in Obstet &amp; Gyne"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Universal screening for cytomegalovirus (CMV) infection in pregnancy is not recommended in most countries. One of the major deterrents is the lack of effective prenatal therapy. The role of valacyclovir therapy in reducing the risk of vertical transmission, symptomatic congenital CMV infection and adverse outcome is controversial. The main aim of this systematic review and meta\u2010analysis was to investigate the safety and effectiveness of prenatal valacyclovir therapy in pregnancies with maternal CMV infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>MEDLINE, EMBASE and Cochrane databases and \n<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/ClinicalTrials.gov\">ClinicalTrials.gov<\/jats:ext-link> were searched. The inclusion criteria were pregnancy with confirmed maternal CMV infection, treated or untreated with valacyclovir. The primary outcome was the incidence of congenital CMV infection confirmed by a positive CMV polymerase chain reaction result of the amniotic fluid. The secondary outcomes were symptomatic and asymptomatic infection, perinatal death, termination of pregnancy, anomalies detected on follow\u2010up ultrasound, on fetal magnetic resonance imaging or at birth, severe and mild\u2010to\u2010moderate symptoms due to congenital CMV infection, neurological, visual and hearing symptoms, and adverse events related to valacyclovir. Risk of bias was assessed using the revised Cochrane risk\u2010of\u2010bias tool for randomized trials (RoB 2) or Risk Of Bias In Non\u2010randomized Studies of Interventions (ROBINS\u2010I) tool, as appropriate. Head\u2010to\u2010head meta\u2010analyses were used to compare the risk of each of the explored outcomes according to whether pregnancies with maternal CMV infection were treated with prenatal valacyclovir therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Eight studies (620 women) were included. Pregnancies treated with valacyclovir had a significantly lower risk of congenital CMV infection compared with those not receiving valacyclovir (three studies; 325 fetuses; pooled odds ratio (OR), 0.37 (95%\u2009CI, 0.21\u20130.64); <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u20090%; <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). When stratifying the analysis according to gestational age at maternal infection, the risk of vertical transmission was significantly lower in pregnancies receiving valacyclovir following first\u2010trimester maternal infection (three studies; 184 fetuses; pooled OR, 0.34 (95%\u2009CI, 0.15\u20130.74); <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u200920.9%; <jats:italic>P<\/jats:italic>\u2009=\u20090.001), while there was no significant difference between the two groups in those acquiring CMV infection in the periconceptional period or in the third trimester of pregnancy. Only one study reported on the risk of vertical transmission in women infected in the second trimester, demonstrating a lower risk of congenital infection in women taking valacyclovir, although this was based on a small number of cases. Pregnancies treated with valacyclovir therapy had an increased likelihood of asymptomatic congenital CMV infection compared with those not receiving valacyclovir (two studies; 132 fetuses; pooled OR, 2.98 (95%\u2009CI, 1.18\u20137.55); <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u20090%; <jats:italic>P<\/jats:italic>\u2009=\u20090.021), while there was no significant difference between the two groups in the risk of perinatal death (<jats:italic>P<\/jats:italic>\u2009=\u20090.923), termination of pregnancy (<jats:italic>P<\/jats:italic>\u2009=\u20090.089), anomalies detected at follow\u2010up imaging assessment during pregnancy or at birth (<jats:italic>P<\/jats:italic>\u2009=\u20090.934) and symptoms due to CMV infection in the newborn (<jats:italic>P<\/jats:italic>\u2009=\u20090.092). The occurrence of all adverse events in pregnant individuals taking valacyclovir was 3.17% (95%\u2009CI, 1.24\u20135.93%) (six studies; 210 women), with 1.71% (95%\u2009CI, 0.41\u20133.39%) experiencing acute renal failure, which resolved after discontinuation of the drug. On GRADE assessment, the quality of evidence showing that valacyclovir reduced the risk of congenital CMV infection and adverse perinatal outcome was very low.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Prenatal valacyclovir administration in pregnancies with maternal CMV infection reduces the risk of congenital CMV infection. Further evidence is needed to elucidate whether valacyclovir can affect the course of infection in the fetus and the risk of symptomatic fetal or neonatal infection. \u00a9 2022 International Society of Ultrasound in Obstetrics and Gynecology.<\/jats:p><\/jats:sec>","DOI":"10.1002\/uog.26136","type":"journal-article","created":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T12:05:50Z","timestamp":1670587550000},"page":"436-444","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":102,"title":["Effectiveness and safety of prenatal valacyclovir for congenital cytomegalovirus infection: systematic review and meta\u2010analysis"],"prefix":"10.1002","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7546-8025","authenticated-orcid":false,"given":"F.","family":"D'Antonio","sequence":"first","affiliation":[{"name":"Center for Fetal Care and High\u2010Risk Pregnancy University of Chieti  Chieti Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Marinceu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology The York Hospital  York UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2329-4470","authenticated-orcid":false,"given":"S.","family":"Prasad","sequence":"additional","affiliation":[{"name":"Fetal Medicine Unit, St George's University Hospitals NHS Foundation Trust, University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2802-7670","authenticated-orcid":false,"given":"A.","family":"Khalil","sequence":"additional","affiliation":[{"name":"Fetal Medicine Unit, St George's University Hospitals NHS Foundation Trust, University of London  London UK"},{"name":"Vascular Biology Research Centre, Molecular and Clinical Sciences Research Institute St George's University of London  London UK"},{"name":"Fetal Medicine Unit, Liverpool Women's Hospital University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,4,3]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/uog.21991"},{"key":"e_1_2_7_3_1","unstructured":"PubChem [Internet].Bethesda (MD): National Library of Medicine (US) National Center for Biotechnology Information; 2004\u2013. 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