Objectives
: To report the spectrum of placental pathology findings in pregnancies complicated by SARS-CoV-2 infection.
Methods
: MEDLINE, EMBASE, Google Scholar and the Web of Science databases were searched up to August 11
th
, 2021. Histopathological anomalies included maternal vascular malperfusion (MVM), fetal vascular malperfusion (FVM), acute inflammatory pathology (AIP), chronic inflammatory pathology (CIP), increased perivillous fibrin and intervillous thrombosis. Sub-analyses including only symptomatic women and high-risk pregnancies were also performed. Histopathological analysis of the placenta included gross examination, histopathology on hematoxylin and eosin (H&E), immunohistochemistry (IHC), fluorescence in-situ hybridization (FISH), qRT-PCR on placental tissue, and transmission electron microscope (TEM). Random-effect meta-analyses were used to analyze the data.
Results
:
Fifty-seven studies (1009 pregnancies) were included. MVM was reported in 31.4% (95% CI 21.0-42.8) of placentas, while FVM was observed in 26.9% of cases (95% CI 19.2-35.4). AIP and CIP were reported in 22.6% (95% CI 16.8-28.9) and 26.2% (95% CI 18.9-34.2) of cases, respectively. Increased perivillous fibrin was observed in 32.7% (95% CI 24.1-42.0) of placentas undergoing histopathological analysis, while intervillous thrombosis were observed in 14.6% (95% CI 10.6-21.8) of cases. Other placental findings, including either basal plate with attached myometrial fibers, microscopic accretism, villous edema, increased circulating nucleated Red Blood Cells or membranes with hemorrhage were reported in 38% (95% CI 28.5-48.0) of cases, while only 17.4% (95% CI 10.9-25.0) did not present any abnormal histological findings. Sub-analyses according to maternal symptoms due to SARS-CoV-2 infection or the presence of a high-risk pregnancy showed similar distribution of the different histopathological anomalies to that reported in the main analysis. The risk of placental histopathological anomalies was also higher when considering only case-control studies comparing women with SARS-CoV-2 infection with healthy controls.
Conclusions
:
A significant proportion of placentas where SARS-CoV-2 occurred during pregnancy shows histopathological findings suggesting placental hypoperfusion and inflammation. Future multicenter prospective blinded studies are needed to correlate these placental lesions with pregnancy outcomes.