Background: The Congenital Human Cytomegalovirus Infection Prevention (CHIP) study, a randomized, blinded, placebo-controlled trial, demonstrated that the efficacy of hyperimmune globulin (HIG) was not different from that of placebo regarding transmission of cytomegalovirus (CMV) from mothers to newborns. Our aim was to analyze histologically HIG effects on placentas collected for the CHIP study. Materials and Methods: Virological and histological analyses were performed on 40 placentas from transmitter and nontransmitter HIG-treated and untreated mothers by assessing the number of CMV-positive cells, tissue viral load, tissue damage, and compensatory mechanisms. Results: The HIG and placebo groups showed no significant differences in the number of CMV-positive cells (median number in 10 fields at 10 high-power fields: 2.5 vs. 2, p = 0.969) and viral load (median load: 5 copies/5 ng vs. 10.5 copies/5 ng, p = 0.874). Regarding histological examination, the scores of parameters related to tissue damage and hypoxic parenchymal compensation were higher in transmitters except for chorangiosis, with statistically significant differences observed for chronic villitis (p = 0.007), calcification (p = 0.011), and the total score of tissue damage (p < 0.001). The HIG and placebo groups showed no significant differences for all tissue damage and compensation parameters and overall scores. Discussion: HIGs are not able to reduce placental viral load and histological damage, which was significantly associated only with infection.

Keywords:
Immunohistochemistry, Infection, PCR, Placenta, Prenatal treatment
1.
Kenneson A, Cannon MJ: Review and meta-analysis of the epidemiology of congenital cytomegalovirus (CMV) infection. Rev Med Virol 2007; 17: 253–276.
2.
Gabrielli L, Bonasoni MP, Santini D, Piccirilli G, Chiereghin A, Petrisli E, Dolcetti R, Guerra B, Piccioli M, Lanari M, Landini MP, Lazzarotto T: Congenital cytomegalovirus infection: patterns of fetal brain damage. Clin Microbiol Infect 2012; 18: 419–427.
3.
Rawlinson WD, Hamilton ST, van Zuylen WJ: Update on treatment of cytomegalovirus infection in pregnancy and of the newborn with congenital cytomegalovirus. Curr Opin Infect Dis 2016; 29: 615–624.
4.
Nigro G, Adler SP, La Torre R, Best AM; Congenital Cytomegalovirus Collaborating Group: Passive immunization during pregnancy for congenital cytomegalovirus infection. N Engl J Med 2005; 353: 1350–1362.
5.
Revello MG, Lazzarotto T, Guerra B, Spinillo A, Ferrazzi E, Kustermann A, Guaschino S, Vergani P, Todros T, Frusca T, Arossa A, Furione M, Rognoni V, Rizzo N, Gabrielli L, Klersy C, Gerna G; CHIP Study Group: A randomized trial of hyperimmune globulin to prevent congenital cytomegalovirus. N Engl J Med 2014; 370: 1316–1326.
6.
Nigro G, Adler SP: Hyperimmunoglobulin for prevention of congenital cytomegalovirus disease. Clin Infect Dis 2013; 57(suppl): 193–195.
7.
Jückstock J, Rothenburger M, Friese K, Traunmüller F: Passive immunization against congenital cytomegalovirus infection: current state of knowledge. Pharmacology 2015; 95: 209–217.
8.
Cekinović D, Golemac M, Pugel EP, Tomac J, Cicin-Sain L, Slavuljica I, Bradford R, Misch S, Winkler TH, Mach M, Britt WJ, Jonjić S: Passive immunization reduces murine cytomegalovirus-induced brain pathology in newborn mice. J Virol 2008; 82: 12172–12180.
9.
Maidji E, Nigro G, Tabata T, McDonagh S, Nozawa N, Shiboski S, Muci S, Anceschi MM, Aziz N, Adler SP, Pereira L: Antibody treatment promotes compensation for human cytomegalovirus-induced pathogenesis and a hypoxia-like condition in placentas with congenital infection. Am J Pathol 2010; 177: 1298–1310.
10.
Gabrielli L, Bonasoni MP, Chiereghin A, Piccirilli G, Santini D, Pavia C, Turello G, Squarzoni D, Lazzarotto T: Salivary glands and human congenital cytomegalovirus infection: what happens in early fetal life? J Med Virol 2017; 89: 318–323.
11.
Turowski G, Berge LN, Helgadottir LB, Jacobsen EM, Roald B: A new, clinically oriented, unifying and simple placental classification system. Placenta 2012; 33: 1026–1035.
12.
Spinillo A, Gardella B, Bariselli S, Alfei A, Silini E, Dal Bello B: Placental histopathological correlates of umbilical artery Doppler velocimetry in pregnancies complicated by fetal growth restriction. Prenat Diagn 2012; 32: 1263–1272.
13.
Redline RW, Heller D, Keating S, Kingdom J: Placental diagnostic criteria and clinical correlation – a workshop report. Placenta 2005; 26(suppl A): 114–117.
14.
Redline RW, Boyd T, Campbell V, Hyde S, Kaplan C, Khong TY, Prashner HR, Waters BL; Society for Pediatric Pathology, Perinatal Section, Maternal Vascular Perfusion Nosology Committee: Maternal vascular underperfusion: nosology and reproducibility of placental reaction patterns. Pediatr Dev Pathol 2004; 7: 237–249.
15.
Redline RW, Ariel I, Baergen RN, Desa DJ, Kraus FT, Roberts DJ, Sander CM: Fetal vascular obstructive lesions: nosology and reproducibility of placental reaction patterns. Pediatr Dev Pathol 2004; 7: 443–452.
16.
Redline RW: Placental pathology: a systematic approach with clinical correlations. Placenta 2008; 29(suppl A): 86–91.
17.
De La Ossa MM, Cabello-Inchausti B, Robinson MJ: Placental chorangiosis. Arch Pathol Lab Med 2001; 125: 1258.
18.
Stanek J: Chorangiosis of chorionic villi: what does it really mean? Arch Pathol Lab Med 2016; 140: 588–593.
19.
Kingdom JC, Kaufmann P: Oxygen and placental villous development: origins of fetal hypoxia. Placenta 1997; 18: 613–621.
20.
Khong TY, Malcomson RDG (eds): Keeling’s Fetal and Neonatal Pathology. Cham, Springer, 2015.
21.
Roberts DJ: Placental pathology, a survival guide. Arch Pathol Lab Med 2008; 132: 641–651.
22.
Zeng J, Marcus A, Buhtoiarova T, Mittal K: Distribution and potential significance of intravillous and intrafibrinous particulate microcalcification. Placenta 2017; 50: 94–98.
23.
Fitzgerald B, Kingdom J, Keating S: Distal villous hypoplasia. Diagn Histopathol 2012; 18: 195–200.
24.
Altshuler G: Chorangiosis. An important placental sign of neonatal morbidity and mortality. Arch Pathol Lab Med 1984; 108: 71–74.
© 2018 S. Karger AG, Basel
2018
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.