Placenta histopathology in SARS-CoV-2 infection: analysis of a consecutive series and comparison with control cohorts

Infection by SARS-CoV-2 has been shown to involve a wide range of organs and tissues, leading to a kaleidoscope of clinical conditions. Within this spectrum, an involvement of the fetal-maternal unit could be expected, but, so far, the histopathological evaluation of placentas delivered by women with SARS-CoV-2 infection did not show distinct hallmarks. A consecutive series of 11 placentas, delivered by 10 women with COVID-19 admitted to our Obstetrics and Gynecology clinic have been investigated and compared to a control cohort of 58 pre-COVID-19 placentas and 28 placentas delivered by women who had a previous cesarean section. Four out of eleven placentas showed changes consistent with chronic villitis/villitis of unknown etiology (VUE), while in one case, chronic histiocytic intervillositis was diagnosed. Thrombo-hemorrhagic alterations were observed in a subset of cases. Compared to the control cohort, chronic villitis/VUE (p < 0.001), chronic deciduitis (p = 0.023), microvascular thrombosis (p = 0.003), presence of infarction areas (p = 0.047) and of accelerated villous maturation (p = 0.005) showed higher frequencies in placentas delivered by women with COVID-19. Chronic villitis/VUE (p = 0.003) and accelerated villous maturation (p = 0.019) remained statistically significant by restricting the analysis to placentas delivered after a previous cesarean section. The observed differences in terms of pathological findings could be consistent with SARS-CoV-2 pathogenesis, but just a subset of alterations remained statistically significant after adjusting for a previous cesarean section. A careful consideration of potential confounders is warranted in future studies exploring the relationship between COVID-19 and pregnancy.

Placenta Pathology From Term Born Neonates With Normal or Adverse Outcome

Background The incidence of umbilical cord or placental parenchyma abnormalities associated with mortality or morbidity of term infants is lacking. Methods Placentas of 55 antepartum stillbirths (APD), 21 intrapartum stillbirths (IPD), 12 neonatal deaths (ND), and 80 admissions to a level 3 neonatal intensive care unit (NS) were studied and compared with 439 placentas from neonates from normal term pregnancies and normal outcome after vaginal delivery (NPVD) and with 105 placentas after an elective caesarian sections (NPEC). Results NPVD and NPEC placentas showed no or one abnormality in 70% and placentas from stillbirth showed two or more abnormalities in 80% of cases. APD placentas more frequently had a low weight and less formation of terminal villi. Hypercoiling was more often present in all study groups. Severe chronic villitis was almost exclusively present in APD placentas. Chorioamnionitis was significantly more frequent in APD, IPD and NS placentas and funisitis was more often observed in IPD and NS placentas. Conclusion Multiple placental abnormalities are significantly more frequent in placentas from term neonates with severe perinatal morbidity and mortality. These placental abnormalities are thought to be associated with disturbed oxygen transfer or with inflammation.

Abstract 16048: Placental Pathology in Pregnancies Complicated by Maternal Cardiac Disease: A Study From the Standardized Outcomes in Reproductive Cardiovascular Care (STORCC) Initiative

Background: The incidence of pregnancy in women with cardiovascular disease (CVD) has increased, yet there is little known about placental pathology in these women. Objective: To describe placental pathology in pregnancies carried by women with CVD and to compare placental findings between categories of maternal CVD. Methods: We identified live births within the prospective, single-center Standardized Outcomes in Reproductive Cardiovascular Care cohort for which the placenta underwent histopathologic examination. Pathology reports were reviewed by an experienced placental pathologist (BJQ) for prespecified pathologic findings that were then compared against maternal characteristics. Results: 271 placentas (Table 1) were identified from pregnancies associated with maternal congenital heart disease (CHD) (65%), arrhythmia (16%), cardiomyopathy (8%), connective tissue disease (7%), and valvular heart disease (4%). Median maternal age at delivery was 32 years (range 19-49). Median gestational age at delivery was 39 weeks (range 25-41). Anatomic pathology, mostly in the form of small placenta by weight, was most common, affecting 43% of placentas. Vascular pathology, mostly maternal vascular malperfusion or fetal flow restriction, was seen in 41% of placentas. Infectious (acute chorioamnionitis) and inflammatory (chronic villitis) pathology was seen in 23% and 10% of placentas, respectively. Inflammatory pathology was more common in maternal CHD than in other CVD categories (14.9% vs. 2.1%, p=0.001), while anatomic, infectious, and vascular pathology were seen at similar rates across all CVD categories. Conclusion: Pregnancies among women with CVD commonly demonstrate abnormal placental findings, especially anatomic and vascular pathology. Chronic villitis was more common in women with CHD compared to other types of CVD. Otherwise, the incidence of specific pathology findings did not differ significantly based on maternal characteristics.

Massive Perivillous Fibrin Deposition in Congenital Cytomegalovirus Infection: A Case Report

Cytomegalovirus (CMV) infection is one of the most common congenital viral infections. Classically associated placental findings include chronic villitis with plasma cells, stromal hemosiderin deposition, and identification of viral inclusions in villous endothelial and stromal cells. We present a case of confirmed congenital CMV infection that lacked these classical findings, but demonstrated massive perivillous fibrin deposition (MPVFD). This is the first report of CMV associated with MPVFD. MPVFD is an uncommon placental lesion associated with adverse fetal outcomes and a high risk of recurrence. However, the recurrence risk in patients with an infectious cause may be lower in than patients with other associated clinical conditions.

Placenta in SARS-CoV-2 infection: a new target for inflammatory and thrombotic events

Infection by SARS-CoV-2 has been shown to involve a wide range of organs and tissues, leading to a kaleidoscope of clinical conditions. Within this spectrum, an increased rate of preterm deliveries has been reported in women with COVID-19. High expression of proteins (ACE2/TMPRSS2) required for SARS- CoV-2 cell entry has been observed in the maternal-fetal tissues, supporting the possibility of placental viral involvement. A consecutive series of 6 placentas, delivered by 5 women with COVID-19 have been investigated. Three out of six placentas showed changes consistent with chronic villitis, while in one case chronic histiocytic intervillositis was diagnosed. Vascular abnormalities consisting of thrombo- hemorrhagic alterations were identified in the three cases with chronic villitis. These pathological findings: i) provide a basis to explain the higher rate of obstetric complications in these patients; 2) suggest the need to investigate heparin use in COVID-19 affected pregnant patients to prevent adverse outcomes.

Seasonal Variation of Chronic Villitis of Unknown Etiology

Introduction Chronic villitis of unknown etiology (VUE) is a chronic inflammatory lesion of the placenta. VUE is hypothesized to result from an alloimmune response or as response to an unidentified infection. Lack of a seasonal trend is thought to support VUE as an alloimmune response, though data on seasonal VUE trends are limited. Methods Data were obtained from a hospital in Chicago, Illinois, from 2011–2016. Placentas sent to pathology were reviewed using a standardized protocol, and VUE cases were identified based on an automated text search of pathology records. We used monthly VUE prevalence estimates to investigate the annual trend, and we used Poisson regression to evaluate seasonal variation in the number of VUE cases. Results There were 79 825 deliveries within the study period. Pathologists evaluated 12 074 placentas and identified 2873 cases of VUE. Regression results indicate that the risk of VUE is 16% to 17% higher in the fall and winter as compared to the summer (fall relative risk [RR]: 1.17, 95% confidence interval [CI]: 1.06–1.29; winter RR: 1.16, 95% CI: 1.05–1.29). Discussion Our results suggest that there may be seasonal variation in VUE prevalence, particularly for low-grade VUE. Future studies should evaluate seasonal variation in a representative sample rather than relying on pathology reports to estimate prevalence.