Late miscarriage and stillbirth in asymptomatic and symptomatic hospitalised pregnant women in Belgium during the first and second waves of COVID-19: a prospective nationwide population-based study.

BACKGROUND: Stillbirth has been recognized as a possible complication of a SARS-CoV-2 infection during pregnancy, probably due to destructive placental lesions (SARS-CoV-2 placentitis). The aim of this work is to analyse stillbirth and late miscarriage cases in unvaccinated pregnant women infected with SARS-CoV-2 during the first two waves (wild-type period) in Belgium. METHODS: Stillbirths and late miscarriages in our prospective observational nationwide registry of SARS-CoV-2 infected pregnant women (n = 982) were classified by three authors using a modified WHO-UMC classification system for standardized case causality assessment. RESULTS: Our cohort included 982 hospitalised pregnant women infected with SARS-CoV-2, with 23 fetal demises (10 late miscarriages from 12 to 22 weeks of gestational age and 13 stillbirths). The stillbirth rate was 9.5‰ for singleton pregnancies and 83.3‰ for multiple pregnancies, which seems higher than for the background population (respectively 5.6‰ and 13.8‰). The agreement between assessors about the causal relationship with SARS-Cov-2 infection was fair (global weighted kappa value of 0.66). Among these demises, 17.4% (4/23) were "certainly" attributable to SARS-CoV-2 infection, 13.0% (3/23) "probably" and 30.4% (7/23) "possibly". Better agreement in the rating was noticed when pathological examination of the placenta and identification of the virus were available, underlining the importance of a thorough investigation in case of intra-uterine fetal demise. CONCLUSIONS: SARS-CoV-2 causality assessment of late miscarriage and stillbirth cases in our Belgian nationwide case series has shown that half of the fetal losses could be attributable to SARS-CoV-2. We must consider in future epidemic emergencies to rigorously investigate cases of intra-uterine fetal demise and to store placental tissue and other material for future analyses.

Influence of maternal psychological distress during COVID-19 pandemic on placental morphometry and texture.

The Coronavirus Disease 2019 (COVID-19) pandemic has been accompanied by increased prenatal maternal distress (PMD). PMD is associated with adverse pregnancy outcomes which may be mediated by the placenta. However, the potential impact of the pandemic on in vivo placental development remains unknown. To examine the impact of the pandemic and PMD on in vivo structural placental development using advanced magnetic resonance imaging (MRI), acquired anatomic images of the placenta from 63 pregnant women without known COVID-19 exposure during the pandemic and 165 pre-pandemic controls. Measures of placental morphometry and texture were extracted. PMD was determined from validated questionnaires. Generalized estimating equations were utilized to compare differences in PMD placental features between COVID-era and pre-pandemic cohorts. Maternal stress and depression scores were significantly higher in the pandemic cohort. Placental volume, thickness, gray level kurtosis, skewness and run length non-uniformity were increased in the pandemic cohort, while placental elongation, mean gray level and long run emphasis were decreased. PMD was a mediator of the association between pandemic status and placental features. Altered in vivo placental structure during the pandemic suggests an underappreciated link between disturbances in maternal environment and perturbed placental development. The long-term impact on offspring is currently under investigation.

The impact of SARS-CoV-2 infection on term placentae.

Background: Coronavirus 2019 infection (COVID 19) is an ongoing pandemic caused by pathogenic RNA viruses called severe acute respiratory syndrome coronavirus-2 (SARS-COV-2). It has affected people of all ages, with high morbidity and mortality among the elderly and immunocompromised population. Limited information is available on the effects of COVID-19 infection on pregnancy. Aim: To describe the histopathological changes in the placental tissue of SARS-CoV-2 infected term mothers with no comorbidities and to correlate with neonatal outcome. Materials and Methods: This observational study was conducted in the Department of Pathology, KMCH institute of health sciences and research, Coimbatore from May 1, 2020 to November 30, 2020 for 6 months. Placental tissues of all COVID-19-positive term mothers with no comorbidities were included in this study. Histopathological examination of placentae was carried out and clinical data of mothers and newborn babies were obtained from medical records. Results: Histopathological examination of 64 placental tissue of COVID-19 mothers showed predominantly the features of fetal vascular malperfusion like stem villi vasculature thrombus, villous congestion, and avascular villi. No significant correlation was obtained in comparison with parity and symptomatic status of the mothers. However, histopathological changes were more prominent among symptomatic patients. The newborn babies born to these mothers showed no adverse outcome. Conclusion: This study concluded that though COVID-19 infection in normal term pregnant women was associated with increased prevalence of features of fetal vascular malperfusion, there was no significant morbidity in the health status of both COVID-19 mothers and their neonates.

Analysis of placental pathology after COVID-19 by timing and severity of infection.

BACKGROUND: COVID-19 during pregnancy can have serious effects on pregnancy outcomes. The placenta acts as an infection barrier to the fetus and may mediate adverse outcomes. Increased frequency of maternal vascular malperfusion has been detected in the placentas of patients with COVID-19 compared with controls, but little is known about how the timing and severity of infection affect placental pathology. OBJECTIVE: This study aimed to examine the effects of SARS-CoV-2 infection on placental pathology, specifically whether the timing and severity of COVID-19 affect pathologic findings and associations with perinatal outcomes. STUDY DESIGN: This was a descriptive retrospective cohort study of pregnant people diagnosed with COVID-19 who delivered between April 2020 and September 2021 at 3 university hospitals. Demographic, placental, delivery, and neonatal outcomes were collected through medical record review. The timing of SARS-CoV-2 infection was noted, and the severity of COVID-19 was categorized on the basis of the National Institutes of Health guidelines. The placentas of all patients with positive nasopharyngeal reverse transcription-polymerase chain reaction COVID-19 testing were sent for gross and microscopic histopathologic examinations at the time of delivery. Nonblinded pathologists categorized histopathologic lesions according to the Amsterdam criteria. Univariate linear regression and chi-square analyses were used to assess how the timing and severity of SARS-CoV-2 infection affected placental pathologic findings. RESULTS: This study included 131 pregnant patients and 138 placentas, with most patients delivered at the University of California, Los Angeles (n=65), followed by the University of California, San Francisco (n=38) and Zuckerberg San Francisco General Hospital (n=28). Most patients were diagnosed with COVID-19 in the third trimester of pregnancy (69%), and most infections were mild (60%). There was no specific placental pathologic feature based on the timing or severity of COVID-19. There was a higher frequency of placental features associated with response to infection in the placentas from infections before 20 weeks of gestation than that from infections after 20 weeks of gestation (P=.001). There was no difference in maternal vascular malperfusion by the timing of infection; however, features of severe maternal vascular malperfusion were only found in the placentas of patients with SARS-CoV-2 infection in the second and third trimesters of pregnancy, not in the placentas of patients with COVID-19 in the first trimester of pregnancy. CONCLUSION: Placentas from patients with COVID-19 showed no specific pathologic feature, regardless of the timing or severity of the disease. There was a higher proportion of placentas from patients with COVID-19-positive tests in earlier gestations with evidence of placental infection-associated features. Future studies should focus on understanding how these placental features in SARS-CoV-2 infections go on to affect pregnancy outcomes.

Predictive factors for severe placental damage in pregnant women with SARS-CoV-2 infection.

INTRODUCTION: SARS-Cov-2 infection during pregnancy can lead to severe placental lesions characterized by massive perivillous fibrin deposition, histiocytic intervillositis and trophoblast necrosis. Diffuse placental damage of this kind is rare, but can sometimes lead to obstetric complications, such as intrauterine fetal death (IUFD). The objectives of this study were to identify possible predictors of severe placental lesions. METHODS: We retrospectively studied 96 placentas from SARS-Cov-2 positive pregnant women who gave birth between March 2020 and March 2022. Cases with and without severe placental lesions were compared in terms of clinical and laboratory findings. RESULTS: Twelve of the 96 patients had severe placental lesions. There was no significant association with diabetes, obesity or severe clinical maternal disease. In contrast, presence of severe placental lesions was significantly associated with neonatal intensive care, cesarean section, prematurity, IUFD, intrauterine growth restriction (IUGR), gestational age, maternal hypofibrinogenemia and thrombocytopenia. No cases of severe placental lesions were observed in vaccinated patients or in those with the Omicron variant. DISCUSSION: In these patients, severe placental lesions due to SARS-Cov-2 were significantly associated with the presence of coagulation abnormalities (hypofibrinogenemia and thrombocytopenia), IUGR and gestational age. These results support laboratory and ultrasound monitoring of these parameters in pregnant women with SARS-Cov-2 infection, especially during the second trimester, to predict potential negative fetal outcomes.

SARS-CoV-2 placentitis and severe pregnancy outcome after maternal infection: A Danish case series.

INTRODUCTION: SARS-CoV-2 infection during pregnancy may cause viral inflammation of the placenta, resulting in fetal demise even without fetal or newborn infection. The impact of timing of the infection and the mechanisms that cause fetal morbidity and mortality are not well understood. MATERIAL AND METHODS: To describe placental pathology from women with confirmed SARS-CoV-2 infection during pregnancy, a SARS-CoV-2 immunohistochemistry-positive placenta and late miscarriage, stillbirth, neonatal death, or medically indicated birth due to fetal distress. RESULTS: The triad of trophoblastic necrosis, inflammatory intervillous infiltrates, and increased perivillous fibrinoid deposition was present in all 17 placentas; the pregnancies resulted in eight stillbirths, two late miscarriages (19 and 21 weeks' gestation), and seven liveborn children, two of which died shortly after delivery. The severity of maternal COVID-19 was not reflected by the extent of the placental lesions. In only one case, SARS-CoV-2 was detected in lung tissue samples from the fetus. The majority events (miscarriage, stillbirth, fetal distress resulting in indicated birth, or livebirth, but neonatal death) happened shortly after maternal SARS-CoV-2 infection was diagnosed. Seven of eight sequenced cases were infected with the Delta (B.1.617.2) virus strain. CONCLUSION: We consolidate findings from previous case series describing extensive SARS-CoV-2 placentitis and placental insufficiency leading to fetal hypoxia. We found sparse evidence to support the notion that SARS-CoV-2 virus had infected the fetus or newborn.

Maternal SARS-CoV-2, Placental Changes and Brain Injury in 2 Neonates.

Long-term neurodevelopmental sequelae are a potential concern in neonates following in utero exposure to severe acute respiratory syndrome coronavirus disease 2 (SARS-CoV-2). We report 2 neonates born to SARS-CoV-2 positive mothers, who displayed early-onset (day 1) seizures, acquired microcephaly, and significant developmental delay over time. Sequential MRI showed severe parenchymal atrophy and cystic encephalomalacia. At birth, neither infant was SARS-CoV-2 positive (nasopharyngeal swab, reverse transcription polymerase chain reaction), but both had detectable SARS-CoV-2 antibodies and increased blood inflammatory markers. Placentas from both mothers showed SARS-CoV-2-nucleocapsid protein and spike glycoprotein 1 in the syncytiotrophoblast, fetal vascular malperfusion, and significantly increased inflammatory and oxidative stress markers pyrin domain containing 1 protein, macrophage inflammatory protein 1 ßη, stromal cell-derived factor 1, interleukin 13, and interleukin 10, whereas human chorionic gonadotropin was markedly decreased. One infant (case 1) experienced sudden unexpected infant death at 13 months of age. The deceased infant's brain showed evidence of SARS-CoV-2 by immunofluorescence, with colocalization of the nucleocapsid protein and spike glycoprotein around the nucleus as well as within the cytoplasm. The constellation of clinical findings, placental pathology, and immunohistochemical changes strongly suggests that second-trimester maternal SARS-CoV-2 infection with placentitis triggered an inflammatory response and oxidative stress injury to the fetoplacental unit that affected the fetal brain. The demonstration of SARS-CoV-2 in the deceased infant's brain also raises the possibility that SARS-CoV-2 infection of the fetal brain directly contributed to ongoing brain injury. In both infants, the neurologic findings at birth mimicked the presentation of hypoxic-ischemic encephalopathy of newborn and neurologic sequelae progressed well beyond the neonatal period.

The effects of preconception and early gestation SARS-CoV-2 infection on pregnancy outcomes and placental pathology.

OBJECTIVE: To evaluate if peri-pregnancy timing of a PCR+ test for SARS-CoV-2 RNA affects pregnancy outcomes and placental pathology. METHODS: This is a retrospective cohort study conducted in a tertiary center. Pregnancy outcomes and placental pathology were compiled for women who tested positive for SARS-CoV-2 RNA from a nasopharyngeal swab assessed by RT-PCR. The population comprised four groups that were PCR+ preconception (T0) or in the 1st (T1), 2nd (T2), or 3rd (T3) trimester of pregnancy. A fifth, control group (TC) tested PCR- for SARS-CoV-2 before delivery. RESULTS: Seventy-one pregnancies were studied. The T0 group exhibited lower gestational ages at delivery, had infants with the lowest birth weights, the highest rate of pregnancy loss before 20 weeks. Features of maternal vascular malperfusion and accelerated villous maturation were prominent findings in the histopathology of placentas from women PCR+ for SARS-CoV-2 RNA, especially in the T0 and the T1 groups. CONCLUSION: Women at highest risk for pregnancy complications are those who test PCR+ for viral RNA preconception or during first trimester of pregnancy.

Placental Histopathology in COVID-19-Positive Mothers.

The placenta is a captivating multifunctional organ of fetal origin and plays an essential role during pregnancy by intimately connecting mother and baby. This study explicates placental pathology and information about 25 placentas collected from the mothers infected with novel coronavirus (SARS-COV-2). So far, congenital transmission of SARS-CoV-2 seems to be remarkably uncommon in spite of many cases of COVID-19 during pregnancy. Out of the 25 placental tissue samples collected, none has shown gene expression of SARS-CoV-2 when confirmed by RT-PCR. At the same time, nasal and throat swab samples collected from newborns of SARS-CoV-2-positive mothers correspondingly tested negative by RT-PCR. The shielding properties of placental barriers against viral infections from mothers to newborns remains a mystery. Major histopathological findings have been recorded as choriodecidual tissue with necrosis, intramural fibrin deposition, chorionic villi with fibrosis, and calcification. Moreover, although recent findings are insufficient to prove direct placental transmission of COVID-19, the abundance of angiotensin-converting enzymes-2 (ACE-2) on the placental surface could potentially contribute to unpleasant outcomes during pregnancy as SARSCoV-2 gains access to human cells via ACE-2. Finally, the significance of these findings is vague and needs further study.

Histomorphological evaluation of placenta in SARS-CoV-2 patients: A cross-sectional study.

Background: SARS-CoV-2 has emerged as a major pandemic of the century and little is known about the impact of maternal infection on placental histopathology. Histopathologic examination of placental tissue can contribute to significant information regarding the pathophysiology of the disease and how it affects the fetal outcome. Materials and Methods: This was a cross-sectional study conducted at the Department of Pathology, Government Doon Medical College and Hospital, Dehradun, on the placenta of 50 coronavirus disease 2019 (COVID-19)-positive pregnant females confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) from August 2020 to October 2020. Fifty term historical placentas were taken as control. Placenta sections were fixed in formalin, processed into paraffin blocks, stained with hematoxylin and eosin (H and E) stain, and visualized for any abnormality. Results: The most prominent histological finding in the placenta of pregnant women affected by COVID-19 was chorangiosis, which is a feature of fetal vascular malperfusion seen in 28 (56%) cases. Other features included maternal vascular malperfusions (MVM) such as villous crowding and agglutination in 12 (24%) cases. Tenney-Parker change was seen in 13 (26%) patients. Intervillous fibrinoid deposition and intervillous hemorrhage were seen in 37 (74%) patients and 7 (14%) patients showed significant calcification. Other findings observed were less common. Conclusion: Infection with SARS-CoV-2 may be associated with a significant impact on fetal and maternal circulation causing features of fetal and maternal malperfusion such as chorangiosis, villous crowding, and agglutination. Indicating that the infection could cause a potential rise in the risk of adverse perinatal outcomes such as intrauterine fetal growth retardation, preterm birth, or stillbirth.

Congenital Rift Valley fever in Sprague Dawley rats is associated with diffuse infection and pathology of the placenta.

Rift Valley fever (RVF) is a disease of animals and humans associated with abortions in ruminants and late-gestation miscarriages in women. Here, we use a rat model of congenital RVF to identify tropisms, pathologies, and immune responses in the placenta during vertical transmission. Infection of late-gestation pregnant rats resulted in vertical transmission to the placenta and widespread infection throughout the decidua, basal zone, and labyrinth zone. Some pups from infected dams appeared normal while others had gross signs of teratogenicity including death. Histopathological lesions were detected in placenta from pups regardless of teratogenicity, while teratogenic pups had widespread hemorrhage throughout multiple placenta layers. Teratogenic events were associated with significant increases in placental pro-inflammatory cytokines, type I interferons, and chemokines. RVFV displays a high degree of tropism for all placental tissue layers and the degree of hemorrhage and inflammatory mediator production is highest in placenta from pups with adverse outcomes. Given the potential for RVFV to emerge in new locations and the recent evidence of emerging viruses, like Zika and SARS-CoV-2, to undergo vertical transmission, this study provides essential understanding regarding the mechanisms by which RVFV crosses the placenta barrier.

SARS-CoV-2 Infection and Pregnancy: Maternal and Neonatal Outcomes and Placental Pathology Correlations.

There is accumulating evidence on the perinatal aspects of COVID-19, but available data are still insufficient. The reports on perinatal aspects of COVID-19 have been published on a small group of patients. Vertical transmission has been noted. The SARS-CoV-2 genome can be detected in umbilical cord blood and at-term placenta, and the infants demonstrate elevated SARS-CoV-2-specific IgG and IgM antibody levels. In this work, the analysis of clinical characteristics of RT-PCR SARS-CoV-2-positive pregnant women and their infants, along with the placental pathology correlation results, including villous trophoblast immunoexpression status for SARS-CoV-2 antibody, is presented. RT-PCR SARS-CoV-2 amniotic fluid testing was performed. Neonatal surveillance of infection status comprised RT-PCR testing of a nasopharyngeal swab and the measuring of levels of anti-SARS-CoV-2 in blood serum. In the initial study group were 161 pregnant women with positive test results. From that group, women who delivered during the hospital stay were selected for further analysis. Clinical data, laboratory results, placental histomorphology results, and neonatal outcomes were compared in women with immunohistochemistry (IHC)-con SARS-CoV-2-positive and IHC SARS-CoV-2-negative placentas (26 cases). A positive placental immunoprofile was noted in 8% of cases (n = 2), whereas 92% of cases were negative (n = 24). Women with placental infection proven by IHC had significantly different pathological findings from those without. One infected neonate was noted (n = 1; 4%). Infection was confirmed in perinatal autopsy, as there was the intrauterine fetal demise. The potential course of the infection with the risk of vertical transmission and implications for fetal-neonatal condition is critical for proper clinical management, which will involve comprehensive, multidisciplinary perinatal care for SARS-CoV-2-positive patients.

Congenital Infection of Severe Acute Respiratory Syndrome Coronavirus 2 With Intrauterine Fetal Death: A Clinicopathological Study With Molecular Analysis.

BACKGROUND: Observations of vertical transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from mother to fetus have recently been described in the literature. However, the consequences of such transmission, whether fetal or neonatal, are poorly understood. METHODS: From a case of in utero fetal death at 24+2 weeks of gestation that occurred 7 days after the diagnosis of symptomatic SARS-CoV-2 infection in the mother, we isolated the incriminating virus by immunochemistry and molecular techniques in several fetal tissues, with a variant analysis of the SARS-CoV-2 genome. RESULTS: The fetal demise could be explained by the presence of placental histological lesions, such as histiocytic intervillositis and trophoblastic necrosis, in addition to fetal tissue damage. We observed mild fetal growth retardation and visceral damage to the liver, causing hepatocellular damage and hemosiderosis. To the best of our knowledge, this is the first report in the literature of fetal demise secondary to maternal-fetal transmission of SARSCoV- 2 with a congenital infection and a pathological description of placental and fetal tissue damage. CONCLUSIONS: SARS-CoV-2 was identified in both specimens using 3 independent techniques (immunochemistry, real-time quantitative polymerase chain reaction, and realtime digital polymerase chain reaction). Furthermore, the incriminating variant has been identified.

Placental pathological findings in coronavirus disease 2019: Perinatal outcomes.

INTRODUCTION: Placental alterations caused by severe acute respiratory coronavirus-2 (SARS-CoV-2) infection have already been described, but most studies used small sample groups and the difference according to the severity of the disease has not been verified. Our objective was to describe placental alterations in patients with coronavirus disease 2019 (COVID-19) and analyze the association of pathological placental findings with the clinical parameters of COVID-19 and perinatal results. METHODS: This was a nested study within a prospective cohort study involving 109 symptomatic pregnant women with COVID-19. The prevalence of observed placental alterations was described, and the associations of pathological findings with the clinical parameters of COVID-19 severity and with perinatal outcomes were assessed. RESULTS: The frequency of types of placental features was poor maternal vascular perfusion in 45% of cases, poor fetal vascular perfusion in 33.9%, hematogenous origin infection in 32.1%, and morphological changes corresponding to ascending infection in 21.1%. Hematogenous infection differed significantly according to COVID-19 severity (p = 0.008), with a prevalence ratio (PR) of 1.74 (95% confidence interval, 1.02-2.98) in the moderate COVID-19 group compared to the mild COVID-19 group. Among the perinatal outcomes, there was an unexpected inverse association between prematurity and placental infection of hematogenous origin, with lower rates of prematurity among cases with inflammation of hematogenous origin (p = 0.029). DISCUSSION: Moderate SARS-Cov-2 infection presented a higher prevalence of placental pathological findings. There was no association of placental findings with adverse perinatal outcomes.

Correlation between Pregnancy Outcome and Placental Pathology in COVID-19 Pregnant Women.

Background: Vertical transmission of several viruses during pregnancy has been shown to cause adverse fetal outcomes. The question about the possibility of a similar outcome in association with SARS-CoV-2 has been raised in recently published articles. Indeed, the rate of transmission through the placenta to the fetus reported in women with COVID-19 has been shown to form a minority. The aim of this study was to explore the possible histopathological changes in the placenta of pregnant women with COVID-19 after delivery and those changes in the umbilical cord. Methods: A case-control study including a total of 50 full-term pregnant women with COVID-19 and 60 control pregnant females. Histopathological evaluation of placental tissues and umbilical cords were reported. Results: The main findings in the umbilical cord were increased thickness of vessels, thrombus formation, endothelins, and narrow lumen; except for the increased thickness of blood vessels, these findings were more frequently seen in women with COVID-19, in comparison with control women in a significant manner (p < 0.05). Increased thickness of blood vessels was more significantly observed in the control group compared to the COVID-19 group (p < 0.01). Findings of the placenta included avascular villi, fibrin, thrombosis, and meconium macrophage in various combinations. Except for fibrin as the sole findings, all other findings including combinations were more frequently encountered in the study group in comparison to the control group (p < 0.05). Conclusion: Pregnant women with COVID-19 have significant pathological alterations in the placenta and umbilical cord. These findings reflect the capability of SARS-CoV-2 in causing immunological reactions to the placenta, either directly or indirectly, and these pathologies may be linked to the higher rate of adverse neonatal outcomes and maternal admission to the intensive care unit.

SARS-CoV-2, Placental Histopathology, Gravity of Infection and Immunopathology: Is There an Association?

(1) Background: As the pandemic months progress, more and more evidence shows that the placenta acts as a "barrier" to SARS-CoV-2, although rare cases of vertical transmission have been described. (2) Methods: In an attempt to investigate whether the symptoms' severity was related to different placental histological characteristics and the immune microenvironment, we subdivided 29 placentas from 29 mothers positive for SARS-CoV-2 into two groups, depending on the symptomatology (moderate/severe vs. asymptomatic/mild), performing immunohistochemical investigations for CD4 + and CD8 + T lymphocytes, as well as for CD68 + macrophage. We also evaluated the immuno-expression of the ACE2 receptor at the placental level. These two groups were compared to a control group of 28 placentas from 28 SARS-CoV-2-negative healthy mothers. (3) Results: The symptoms (likely to be related to viremia) were statistically significantly correlated (p < 0.05) with histopathological changes, such as maternal malperfusion, decidual arteriopathy, blood vessel thrombus of fetal relevance. Furthermore, the immuno-expression of ACE2 was significantly lower in SARS-CoV-2-positive groups vs. control group (p = 0.001). (4) Conclusions: There is still much to study and discover regarding the relationship between SARS-CoV-2 and histological changes in placentas and how the latter might contribute to various neonatal clinical outcomes, such as prematurity.

The placental pathology in Coronavirus disease 2019 infected mothers and its impact on pregnancy outcome.

INTRODUCTION: This study aims at observing placental pathologies in COVID-19 infected women, and analyzing its impact on pregnancy outcome. METHOD: This is a descriptive-analytical study done at a tertiary centre of Northern India. All COVID-19 positive pregnant women with gestational age ≥20 weeks, with placental histopathological reporting, were included in this study. A total of 173 COVID-19 pregnant women were included in the study. RESULTS: Placental abnormalities were noticed in 49·16% of total 179 placentae examined. Maternal vascular malperfusion (27·93%) was the most observed placental pathology followed by villous fibrin deposits (22·90%), fetal vasculopathy (16·75%), and acute inflammation (6·70%). Stillbirths were 22 and NICU admissions were seen in 50 neonates. Abnormal placental abnormalities led to higher stillbirths (p value 0·011) and lower Apgar scores at 1 and 5 min (p-value 0·028; p-value 0·002, respectively). Intervillous fibrin deposits had higher risk associated with lower Apgar score at 1 and 5 min [RR 2·05 (95% CI 1·21-3·48, p-value 0·010) and RR 5·52 (95% CI 2·58-11·81, p-value <0·001), respectively]. RP clot/hemorrhage was also associated with lower Apgar score at 1 and 5 min [RR 2·61 (95% CI 1·52-4·49, p-value 0·002) and RR 3.54 (95% CI 1·66-7·55, p-value 0·001), respectively]. DISCUSSION: Placental abnormalities in COVID-19 infection were associated with significant higher incidence of unexplained stillbirths, and lower Apgar scores. Although, this is the largest descriptive-analytical study done so far, comparative studies are required to draw a clear conclusion regarding the impact of COVID-19 infection on human placenta and its effect on pregnancy outcomes.

Placental pathology in a pregnant woman with severe COVID-19 and successful ECMO treatment: a case report.

BACKGROUND: Infection with SARS-CoV-2 during pregnancy can lead to a severe condition in the patient, which is challenging for obstetricians and anaesthesiologists. Upon severe COVID-19 and a lack of improvement after multidrug therapy and mechanical ventilation, extracorporeal membrane oxygenation (ECMO) is introduced as the last option. Such treatment is critical in women with very preterm pregnancy when each additional day of the intrauterine stay is vital for the survival of the newborn. CASE PRESENTATION: We report a case of a 38-year-old woman at 27 weeks of gestation treated with multidrug therapy and ECMO. The woman was admitted to the intensive care unit (ICU) with increasing fever, cough and dyspnoea. The course of the pregnancy was uncomplicated. She was otherwise healthy. At admission, she presented with severe dyspnoea, with oxygen saturation (SpO2) of 95% on passive oxygenation, heart rate of 145/min, and blood pressure of 145/90. After confirmation of SARS-CoV-2 infection, she received steroids, remdesivir and convalescent plasma therapy. The foetus was in good condition. No signs of an intrauterine infection were visible. Due to tachypnea of 40/min and SpO2 of 90%, the woman was intubated and mechanically ventilated. Due to circulatory failure, the prothrombotic activity of the coagulation system, further saturation worsening, and poor control of sedation, she was qualified for veno-venous ECMO. An elective caesarean section was performed at 29 weeks on ECMO treatment in the ICU. A preterm female newborn was delivered with an Apgar score of 7 and a birth weight of 1440 g. The newborn had no laboratory or clinical evidence of COVID-19. The placenta showed the following pathological changes: large subchorionic haematoma, maternal vascular malperfusion, marginal cord insertion, and chorangioma. CONCLUSIONS: This case presents the successful use of ECMO in a pregnant woman with acute respiratory distress syndrome in the course of severe COVID-19. Further research is required to explain the aetiology of placental disorders (e.g., maternal vascular malperfusion lesions or thrombotic influence of COVID-19). ECMO treatment in pregnant women remains challenging; thus, it should be used with caution. Long-term assessment may help to evaluate the safety of the ECMO procedure in pregnant women.

Gestational SARS-CoV-2 infection is associated with placental expression of immune and trophoblast genes.

INTRODUCTION: Maternal SARS-CoV-2 infection during pregnancy is associated with adverse pregnancy outcomes and can have effects on the placenta, even in the absence of severe disease or vertical transmission to the fetus. This study aimed to evaluate histopathologic and molecular effects in the placenta after SARS-CoV-2 infection during pregnancy. METHODS: We performed a study of 45 pregnant participants from the Generation C prospective cohort study at the Mount Sinai Health System in New York City. We compared histologic features and the expression of 48 immune and trophoblast genes in placentas delivered from 15 SARS-CoV-2 IgG antibody positive and 30 IgG SARS-CoV-2 antibody negative mothers. Statistical analyses were performed using Fisher's exact tests, Spearman correlations and linear regression models. RESULTS: The median gestational age at the time of SARS-CoV-2 IgG serology test was 35 weeks. Two of the IgG positive participants also had a positive RT-PCR nasal swab at delivery. 82.2% of the infants were delivered at term (≥37 weeks), and gestational age at delivery did not differ between the SARS-CoV-2 antibody positive and negative groups. No significant differences were detected between the groups in placental histopathology features. Differential expression analyses revealed decreased expression of two trophoblast genes (PSG3 and CGB3) and increased expression of three immune genes (CXCL10, TLR3 and DDX58) in placentas delivered from SARS-CoV-2 IgG positive participants. DISCUSSION: SARS-CoV-2 infection during pregnancy is associated with gene expression changes of immune and trophoblast genes in the placenta at birth which could potentially contribute to long-term health effects in the offspring.