Placental Tissue Destruction and Insufficiency From COVID-19 Causes Stillbirth and Neonatal Death From Hypoxic-Ischemic Injury: A Study of 68 Cases With SARS-CoV-2 Placentitis From 12 Countries

David A. Schwartz*, Elyzabeth Avvad-Portari, Pavel Babal, Marcella Baldewijns, Marie Blomberg, Amine Bouachba, Jessica Camacho, Sophie Collardeau-Frachon, Arthur Colson, Isabelle Dehaene, Joan Carles Ferreres, Brendan Fitzgerald, Marta Garrido-Pontnou, Hazem Gergis, Beata Hargitai, A. Cecilia Helguera-Repetto, Sandra Holmstrom, Claudine Liliane Irles, Asa Leijonhfvud, Sasha LibbrechtTamas Marton, Noel McEntagart, James T. Molina, Raffaella Morotti, Alfons Nadal, Alexandra Navarro, Maria Nelander, Angelica Oviedo, Andre Ricardo Oyamada Otani, Nikos Papadogiannakis, Astrid C. Petersen, Drucilla J. Roberts, Ali G. Saad, Anna Sand, Sam Schoenmakers, Jennifer K. Sehn, Preston R. Simpson, Kristen Thomas, M. Yolotzin Valdespino-Vazquez, Lotte E. Van der Meeren, Jo Van Dorpe, Robert M. Verdijk, Jaclyn C. Watkins, Mehreen Zaigham

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Context.-Perinatal death is an increasingly important problem as the coronavirus disease 2019 (COVID-19) pandemic continues, but the mechanism of death has been unclear. Objective.-To evaluate the role of the placenta in causing stillbirth and neonatal death following maternal infection with COVID-19 and confirmed placental positivity for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Design.-Case-based retrospective clinicopathologic analysis by a multinational group of 44 perinatal specialists from 12 countries of placental and autopsy pathology findings from 64 stillborns and 4 neonatal deaths having placentas testing positive for SARS-CoV-2 following delivery to mothers with COVID-19. Results.-Of the 3 findings constituting SARS-CoV-2 placentitis, all 68 placentas had increased fibrin deposition and villous trophoblast necrosis and 66 had chronic histiocytic intervillositis. Sixty-three placentas had massive perivillous fibrin deposition. Severe destructive placental disease from SARS-CoV-2 placentitis averaged 77.7% tissue involvement. Other findings included multiple intervillous thrombi (37%; 25 of 68) and chronic villitis (32%; 22 of 68). The majority (19; 63%) of the 30 autopsies revealed no significant fetal abnormalities except for intrauterine hypoxia and asphyxia. Among all 68 cases, SARS-CoV-2 was detected from a body specimen in 16 of 28 cases tested, most frequently from nasopharyngeal swabs. Four autopsied stillborns had SARS-CoV-2 identified in internal organs. Conclusions.-The pathology abnormalities composing SARS-CoV-2 placentitis cause widespread and severe placental destruction resulting in placental malperfusion and insufficiency. In these cases, intrauterine and perinatal death likely results directly from placental insufficiency and fetal hypoxic-ischemic injury. There was no evidence that SARS-CoV-2 involvement of the fetus had a role in causing these deaths.

Original languageEnglish
Pages (from-to)660-676
Number of pages17
JournalArchives of Pathology and Laboratory Medicine
Volume146
Issue number6
DOIs
Publication statusPublished - Jun 2022

Bibliographical note

Funding Information:
Babál received support from Slovak Research and Development Agency grant PP-COVID-20-051. Colson received support from the Belgian Fund for Scientific Research (FNRS-F.R.S., grant number 40002773) and the Fetus for Life charity. The other authors have no relevant financial interest in the products or companies described in this article.

Publisher Copyright:
© 2022 College of American Pathologists. All rights reserved.

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