Abstract
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.
Keywords: COVID-19; SARS-CoV-2; fetal vascular malperfusion; maternal vascular malperfusion; perinatal infection; placental histopathology; pregnancy outcomes.
【저자키워드】 COVID-19, SARS-CoV-2, Maternal vascular malperfusion, fetal vascular malperfusion, perinatal infection, placental histopathology, pregnancy outcomes., 【초록키워드】 Inflammation, immunohistochemistry, pathology, thrombosis, Placenta, SARS-COV-2 infection, risk, Transmission, Symptom, database, Histopathology, pregnant women, outcomes, Maternal, Pregnancy, symptomatic, edema, membrane, placental, red blood cells, women, multicenter, distribution, Other, Quantitative, case-control study, Analysis, hemorrhage, Microscope, Google Scholar, lesion, Anomaly, Hematoxylin and eosin, Web of Science, Vascular, 95% confidence interval, eligibility, healthy controls, circulating, pregnancies, inflammatory pathology, placental tissue, histologic findings, Histopathologic analysis, Future, main analysis, performed, blinded, proportion, reported, were used, searched, Increased, fetal, meta-analysis, 【제목키워드】 Meta-analysis, SARS-COV-2 infection, systematic review, Histopathology,