{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T15:49:30Z","timestamp":1791992970356,"version":"4.4.0"},"reference-count":24,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T00:00:00Z","timestamp":1685664000000},"content-version":"vor","delay-in-days":1,"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":[[2023,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To evaluate the correlation of periventricular echogenic halo (halo sign) with histopathological findings and its association with other brain imaging abnormalities in fetuses with cytomegalovirus (CMV) infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This was a retrospective study of fetuses diagnosed with severe CMV infection based on central nervous system (CNS) abnormalities seen on ultrasound, which had termination of pregnancy (TOP) or fetal demise at a single center from 2006 to 2021. All included cases had been evaluated by conventional complete fetal autopsy. A maternal\u2013fetal medicine expert reanalyzed the images from the transabdominal and transvaginal neurosonography scans, blinded to the histological findings. The halo sign was defined as the presence of homogeneous periventricular echogenicity observed in all three fetal brain orthogonal planes (axial, parasagittal and coronal). Cases were classified according to whether the halo sign was the only CNS finding (isolated halo sign) or concomitant CNS anomalies were present (non\u2010isolated halo sign). An expert fetal radiologist reanalyzed magnetic resonance imaging (MRI) examinations when available, blinded to the ultrasound and histological results. Hematoxylin\u2013eosin\u2010stained histologic slides were reviewed independently by two experienced pathologists blinded to the neuroimaging results. Ventriculitis was classified into four grades (Grades 0\u20133) according to the presence and extent of inflammation. Brain damage was categorized into two stages (Stage I, mild; Stage II, severe) according to the histopathological severity and progression of brain lesions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Thirty\u2010five CMV\u2010infected fetuses were included in the study, of which 25 were diagnosed in the second and 10 in the third trimester. One fetus underwent intrauterine demise and TOP was carried out in 34 cases. The halo sign was detected on ultrasound in 32 (91%) fetuses (23 in the second trimester and nine in the third), and it was an isolated sonographic finding in six of these cases, all in the second trimester. The median gestational age at ultrasound diagnosis of the halo sign was similar between fetuses in which this was an isolated and those in which it was a non\u2010isolated CNS finding (22.6 <jats:italic>vs<\/jats:italic> 24.4\u2009weeks; <jats:italic>P<\/jats:italic>\u2009=\u20090.10). In fetuses with a non\u2010isolated halo sign, the severity of additional ultrasound findings was not associated with the trimester at diagnosis, except for microencephaly, which was more frequent in the second compared with the third trimester (10\/18 (56%) <jats:italic>vs<\/jats:italic> 1\/8 (13%); <jats:italic>P<\/jats:italic>\u2009=\u20090.04). With respect to histopathological findings, ventriculitis was observed in all fetuses with an isolated halo sign, but this was mild (Grade 1) in the majority of cases (4\/6 (67%)). Extensive ventriculitis (Grade 2 or 3) was more frequent in fetuses with a non\u2010isolated halo sign (21\/26 (81%)) and those without a periventricular echogenic halo (2\/3 (67%); <jats:italic>P<\/jats:italic>\u2009=\u20090.032). All fetuses with an isolated halo sign were classified as histopathological Stage I with no signs of brain calcifications, white\u2010matter necrosis or cortical injury. On the other hand, 25\/26 fetuses with a non\u2010isolated halo sign and all three fetuses without a periventricular echogenic halo showed severe brain lesions and were categorized as histopathological Stage II. Among fetuses with a non\u2010isolated halo, histological brain lesions did not progress with gestational age, although white\u2010matter necrosis was more frequent, albeit non\u2010significantly, in fetuses diagnosed in the second <jats:italic>vs<\/jats:italic> the third trimester (10\/15 (67%) <jats:italic>vs<\/jats:italic> 3\/11 (27%); <jats:italic>P<\/jats:italic>\u2009=\u20090.06).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In CMV\u2010infected fetuses, an isolated periventricular echogenic halo was observed only in the second trimester and was associated with mild ventriculitis without signs of white\u2010matter calcifications or necrosis. When considering pregnancy continuation, detailed neurosonographic follow\u2010up complemented by MRI examination in the early third trimester is indicated. The prognostic significance of the halo sign as an isolated finding is still to be determined. \u00a9 2023 International Society of Ultrasound in Obstetrics and Gynecology.<\/jats:p><\/jats:sec>","DOI":"10.1002\/uog.26173","type":"journal-article","created":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T18:26:17Z","timestamp":1675362377000},"page":"749-757","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Halo sign in fetal cytomegalovirus infection: cerebral imaging abnormalities and postmortem histopathology in 35 infected fetuses"],"prefix":"10.1002","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9823-4846","authenticated-orcid":false,"given":"A.","family":"Hawkins\u2010Villarreal","sequence":"first","affiliation":[{"name":"BCNatal: Fetal Medicine Research Center, Hospital Cl\u00ednic and Hospital Sant Joan de D\u00e9u Universitat de Barcelona  Barcelona Spain"},{"name":"Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS)  Barcelona Spain"},{"name":"Fetal Medicine Service, Obstetrics Department, Hospital Santo Tom\u00e1s University of Panama  Panama City Panam\u00e1"},{"name":"Iberoamerican Research Network in Obstetrics Gynecology and Translational Medicine  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7160-8839","authenticated-orcid":false,"given":"K.","family":"Castillo","sequence":"additional","affiliation":[{"name":"BCNatal: Fetal Medicine Research Center, Hospital Cl\u00ednic and Hospital Sant Joan de D\u00e9u Universitat de Barcelona  Barcelona Spain"},{"name":"Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Nadal","sequence":"additional","affiliation":[{"name":"Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS)  Barcelona Spain"},{"name":"Department of Basic Clinical Practice University of Barcelona  Barcelona Spain"},{"name":"Department of Pathology Hospital Cl\u00ednic  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Planas","sequence":"additional","affiliation":[{"name":"Department of Anatomical Pathology Hospital Sant Joan de D\u00e9u  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. L.","family":"Moreno\u2010Espinosa","sequence":"additional","affiliation":[{"name":"BCNatal: Fetal Medicine Research Center, Hospital Cl\u00ednic and Hospital Sant Joan de D\u00e9u Universitat de Barcelona  Barcelona Spain"},{"name":"Fetal Medicine Service, Obstetrics Department, Hospital Santo Tom\u00e1s University of Panama  Panama City Panam\u00e1"},{"name":"Iberoamerican Research Network in Obstetrics Gynecology and Translational Medicine  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Alarc\u00f3n","sequence":"additional","affiliation":[{"name":"BCNatal: Fetal Medicine Research Center, Hospital Cl\u00ednic and Hospital Sant Joan de D\u00e9u Universitat de Barcelona  Barcelona Spain"},{"name":"Institut de Recerca Sant Joan de D\u00e9u  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Rebollo\u2010Polo","sequence":"additional","affiliation":[{"name":"Diagnostic Imaging and Image Guided 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