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Updated: Oct 23, 2025
Human Placental and Decidual Organ Cultures to Study Infections at the Maternal-fetal Interface
Published on: July 21, 2016
Placental histopathology after SARS-CoV-2 infection in pregnancy: a systematic review and meta-analysis
Raffaella Di Girolamo1, Asma Khalil2, Sara Alameddine1
1Center for Fetal Care and High-Risk Pregnancy, Department of Obstetrics and Gynecology, University "G. d'Annunzio" of Chieti-Pescara, Chieti, Italy (Ms Di Girolamo, Ms Alameddine, Ms Galliani, Ms Matarrelli, Mr Buca, Dr Liberati, and Dr D'Antonio).
Objective:
This study aimed to report the spectrum of placental pathology findings in pregnancies complicated by SARS-CoV-2 infection.
Data Sources:
MEDLINE, Embase, Google Scholar, and the Web of Science databases were searched up to August 11, 2021.
Study Eligibility Criteria:
Histopathologic anomalies included maternal vascular malperfusion, fetal vascular malperfusion, acute inflammatory pathology, chronic inflammatory pathology, increased perivillous fibrin, and intervillous thrombosis. Moreover, subanalyses of symptomatic women only and high-risk pregnancies were performed.
Methods:
Histopathologic analysis of the placenta included gross examination, histopathology on hematoxylin and eosin, immunohistochemistry, fluorescence in situ hybridization, quantitative reverse transcription-polymerase chain reaction on placental tissue, and transmission electron microscope. Random-effect meta-analyses were used to analyze the data.
Results:
A total of 56 studies (1008 pregnancies) were included. Maternal vascular malperfusion was reported in 30.7% of placentas (95% confidence interval, 20.3-42.1), whereas fetal vascular malperfusion was observed in 27.08 % of cases (95% confidence interval, 19.2-35.6). Acute and chronic inflammatory pathologies were reported in 22.68% (95% confidence interval, 16.9-29.0) and 25.65% (95% confidence interval, 18.4-33.6) of cases, respectively. Increased perivillous fibrin was observed in 32.7% (95% confidence interval, 24.1-42.0) of placentas undergoing histopathologic analysis, whereas intervillous thrombosis was observed in 14.6% of cases (95% confidence interval, 9.7-20.2). Other placental findings, including a basal plate with attached myometrial fibers, microscopic accretism, villous edema, increased circulating nucleated red blood cells, or membranes with hemorrhage, were reported in 37.5% of cases (95% confidence interval, 28.0-47.5), whereas only 17.5% of cases (95% confidence interval, 10.9-25.2) did not present any abnormal histologic findings. The subanalyses according to maternal symptoms owing to SARS-CoV-2 infection or the presence of a high-risk pregnancy showed a similar distribution of the different histopathologic anomalies to that reported in the main analysis. Moreover, the risk of placental histopathologic anomalies was higher when considering only case-control studies comparing women with SARS-CoV-2 infection with healthy controls.
Conclusion:
In pregnant women with SARS-CoV-2 infection, a significant proportion of placentas showed histopathologic findings, suggesting placental hypoperfusion and inflammation. Future multicenter prospective blinded studies are needed to correlate these placental lesions with pregnancy outcomes.
