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 Babál, Marcella Baldewijns, Marie Blomberg, Amine Bouachba, Jessica Camacho, Sophie Collardeau-Frachon, Arthur Colson, Isabelle Dehaene, Joan Carles Ferreres, Brendan Fitzgerald, Marta Garrido-Pontnou, Hazem Gerges, Beata Hargitai, A Cecilia Helguera-Repetto, Sandra Holmström, Claudine Liliane Irles, Åsa Leijonhfvud, Sasha LibbrechtTamás 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-Vázquez, Lotte E van der Meeren, Jo Van Dorpe, Robert M Verdijk, Jaclyn C Watkins, Mehreen Zaigham

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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 & laboratory medicine
Volume146
Issue number6
Early online date10 Feb 2022
DOIs
Publication statusPublished - 1 Jun 2022

Keywords

  • COVID-19
  • Female
  • Fibrin
  • Humans
  • Hypoxia/pathology
  • Infant, Newborn
  • Infectious Disease Transmission, Vertical
  • Perinatal Death
  • Placenta/pathology
  • Pregnancy
  • Pregnancy Complications, Infectious/pathology
  • Retrospective Studies
  • SARS-CoV-2
  • Stillbirth

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