Placental Tissue Destruction and Insufficiency From COVID-19 Causes Stillbirth and Neonatal Death From Hypoxic-Ischemic Injury

Arch Pathol Lab Med. 2022 Jun 1;146(6):660-676. doi: 10.5858/arpa.2022-0029-SA.

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.

MeSH terms

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

Substances

  • Fibrin