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
D. A. Schwartz
(1)
,
E. Avvad-Portari
(2)
,
P. Babál
(3)
,
M. Baldewijns
(4)
,
M. Blomberg
(5)
,
A. Bouachba
(6, 7)
,
J. Camacho
(8)
,
S. Collardeau-Frachon
(9, 7, 10)
,
A. Colson
(11)
,
I. Dehaene
(12)
,
J. C. Ferreres
(13, 14)
,
B. Fitzgerald
(15)
,
M. Garrido-Pontnou
(8, 14)
,
H. Gergis
(16)
,
B. Hargitai
(17)
,
A. C. Helguera-Repetto
(18)
,
S. Holmström
(19)
,
C. L. Irles
(20)
,
Å Leijonhfvud
(21, 22)
,
S. Libbrecht
(23)
,
T. Marton
(17)
,
N. Mcentagart
(24)
,
J. T. Molina
(25)
,
R. Morotti
(26)
,
A. Nadal
(27, 28)
,
A. Navarro
(8)
,
M. Nelander
(29)
,
A. Oviedo
(30)
,
A. R. Oyamada Otani
(31)
,
N. Papadogiannakis
(32)
,
A. C. Petersen
(33)
,
D. J. Roberts
(34, 35)
,
A. G. Saad
(36)
,
A. Sand
(37, 32)
,
S. Schoenmakers
(38)
,
J. K. Sehn
(39)
,
P. R. Simpson
(40)
,
K. Thomas
(41)
,
M. Y. Valdespino-Vázquez
(18)
,
L. E. van Der Meeren
(42, 43)
,
J. van Dorpe
(12)
,
R. M. Verdijk
(38)
,
J. C. Watkins
(34, 35)
,
M. Zaigham
(22, 22, 44)
1
Augusta University - Medical College of Georgia
2 2FI - Fernandes Figueira Institute [Rio de Janeiro, Brazil]
3 Comenius University in Bratislava
4 University Hospitals Leuven [Leuven]
5 LIU - Linköping University
6 HCL - Hospices Civils de Lyon
7 SOFFOET - Société Française de Foetopathologie [Paris]
8 Vall d'Hebron University Hospital [Barcelona]
9 CarMeN - Cardiovasculaire, métabolisme, diabétologie et nutrition
10 HFME - Hôpital Femme Mère Enfant [CHU - HCL]
11 IREC - Institut de Recherche Expérimentale et Clinique
12 Ghent University Hospital
13 HUPTS - Hospital Universitari Parc Taulí de Sabadell [Barcelona, Spain]
14 UAB - Universitat Autònoma de Barcelona = Autonomous University of Barcelona = Universidad Autónoma de Barcelona
15 UCC - University College Cork
16 DBTH - Doncaster and Bassetlaw Teaching Hospitals NHS Foundation Trust [Doncaster, UK]
17 Birmingham Women's and Children's NHS Foundation Trust
18 NIP - National Institute of Perinatology [Mexico City, Mexico]
19 2H - Halland Hospital [Varberg, Sweden]
20 NIP-IER - National Institute of Perinatology "Isidro Espinosa de los Reyes" [Mexico City, Mexico]
21 2H - Hôpital de Helsingborg [Lund, Sweden]
22 Skane University Hospital [Lund]
23 UZA - Antwerp University Hospital [Edegem]
24 RH - Rotunda Hospital [Dublin, Republic of Ireland]
25 BPA - Beaumont Pathology Associates [Beaumont, TX, USA]
26 Department of Neuroscience, Yale University School of Medicine
27 Hospital Clinic [Barcelona, Spain]
28 IDIBAPS - Institut d'Investigacions Biomèdiques August Pi i Sunyer
29 Uppsala University
30 BCOM - Burrell College of Osteopathic Medicine [Las Cruces, New Mexico]
31 LFC - Laboratório Ferdinando Costa [São Paulo, Brazil]
32 Karolinska University Hospital [Stockholm]
33 AAU - Aalborg University [Denmark]
34 Massachusetts General Hospital [Boston]
35 HMS - Harvard Medical School [Boston]
36 UMMSM - University of Miami Leonard M. Miller School of Medicine
37 Karolinska Institute
38 Erasmus MC - Erasmus University Medical Center [Rotterdam]
39 Washington University School of Medicine in St. Louis
40 CHRISTUS HSE - CHRISTUS Hospital St Elizabeth [Beaumont, TX, USA]
41 NYU Langone Medical Center - New York University Langone Medical Center
42 LUMC - Leiden University Medical Center
43 University Medical Center [Utrecht]
44 Skane University Hospital [Malmo]
2 2FI - Fernandes Figueira Institute [Rio de Janeiro, Brazil]
3 Comenius University in Bratislava
4 University Hospitals Leuven [Leuven]
5 LIU - Linköping University
6 HCL - Hospices Civils de Lyon
7 SOFFOET - Société Française de Foetopathologie [Paris]
8 Vall d'Hebron University Hospital [Barcelona]
9 CarMeN - Cardiovasculaire, métabolisme, diabétologie et nutrition
10 HFME - Hôpital Femme Mère Enfant [CHU - HCL]
11 IREC - Institut de Recherche Expérimentale et Clinique
12 Ghent University Hospital
13 HUPTS - Hospital Universitari Parc Taulí de Sabadell [Barcelona, Spain]
14 UAB - Universitat Autònoma de Barcelona = Autonomous University of Barcelona = Universidad Autónoma de Barcelona
15 UCC - University College Cork
16 DBTH - Doncaster and Bassetlaw Teaching Hospitals NHS Foundation Trust [Doncaster, UK]
17 Birmingham Women's and Children's NHS Foundation Trust
18 NIP - National Institute of Perinatology [Mexico City, Mexico]
19 2H - Halland Hospital [Varberg, Sweden]
20 NIP-IER - National Institute of Perinatology "Isidro Espinosa de los Reyes" [Mexico City, Mexico]
21 2H - Hôpital de Helsingborg [Lund, Sweden]
22 Skane University Hospital [Lund]
23 UZA - Antwerp University Hospital [Edegem]
24 RH - Rotunda Hospital [Dublin, Republic of Ireland]
25 BPA - Beaumont Pathology Associates [Beaumont, TX, USA]
26 Department of Neuroscience, Yale University School of Medicine
27 Hospital Clinic [Barcelona, Spain]
28 IDIBAPS - Institut d'Investigacions Biomèdiques August Pi i Sunyer
29 Uppsala University
30 BCOM - Burrell College of Osteopathic Medicine [Las Cruces, New Mexico]
31 LFC - Laboratório Ferdinando Costa [São Paulo, Brazil]
32 Karolinska University Hospital [Stockholm]
33 AAU - Aalborg University [Denmark]
34 Massachusetts General Hospital [Boston]
35 HMS - Harvard Medical School [Boston]
36 UMMSM - University of Miami Leonard M. Miller School of Medicine
37 Karolinska Institute
38 Erasmus MC - Erasmus University Medical Center [Rotterdam]
39 Washington University School of Medicine in St. Louis
40 CHRISTUS HSE - CHRISTUS Hospital St Elizabeth [Beaumont, TX, USA]
41 NYU Langone Medical Center - New York University Langone Medical Center
42 LUMC - Leiden University Medical Center
43 University Medical Center [Utrecht]
44 Skane University Hospital [Malmo]
Résumé
CONTEXT.—: Perinatal death is an increasingly important problem as the 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 SARS-CoV-2. DESIGN.—: Case-based retrospective clinico-pathological 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.—: All 68 placentas had increased fibrin deposition and villous trophoblast necrosis and 66 had chronic histiocytic intervillositis, the three findings constituting SARS-CoV-2 placentitis. 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%; 25/68) and chronic villitis (32%; 22/68). 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.
Domaines
Sciences du Vivant [q-bio]
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