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Case Report: Since the beginning of the Coronavirus Disease 2019 (COVID-19) pandemic, there has been much work to understand the negative effects of SARS-CoV-2 on tissues expressing the Angiotensin Converting Enzyme-2 (ACE2) receptor, including the placenta. However, there is limited information regarding placental pathology findings in mothers with COVID-19 and the effects of SARS-CoV-2 on the placenta. The available research reports effects on the fetus ranging from minimal to intrauterine fetal demise. Case Description: A 4680g baby boy was born at 38+1 weeks of gestation to 36y old G4P1021 female via repeat cesarian section. The pregnancy was complicated by advanced maternal age, chronic hypertension with superimposed pre-eclampsia with severe features, BMI of 80, and SARS-CoV-2 infection. The mother had mild COVID-19 symptoms and did not require hospitalization or oxygen support. Prenatal ultrasounds were limited due to body habitus. At the time of delivery, there was clear amniotic fluid. Upon delivery the infant was cyanotic and limp and was brought to the warmer immediately. Non-invasive positive pressure ventilation was initiated at 5 minutes of life with improvement in infant color and oxygen saturation. He was then admitted to the Neonatal Intensive Care Unit (NICU). APGARs were 2, 3, 5, and 7 at 1, 5, 10, and 15 minutes respectively. Cord gases showed severe metabolic acidosis. The patient was diagnosed with hypoxic-ischemic encephalopathy (HIE) and therapeutic hypothermia was initiated. Both the NICU and obstetric teams were unable to identify a clear perinatal cause of HIE in this patient. Later, the placenta pathology report revealed a large placenta for estimated gestational age corresponding to the 75th percentile, villous parenchyma with focal chorangiosis and thrombi, with unremarkable fetal membrane and three vessel umbilical cord. The cause of HIE was then thought to be due to the placental thrombi likely caused by SARS-CoV-2 infection. Discussion(s): Fetal vascular malperfusion and fetal vascular thrombus have been noted as a common finding in the placentas of pregnant women who test positive for SARS-CoV-2. There are various causes of HIE, from maternal, placental and fetal factors. This patient had no clinically evident hypoxic event, but information was limited due to the lack of monitoring of the fetus in utero. Given the mother's SARS-CoV-2 infection and the placental pathology findings, it is likely that the cause of this patient's HIE was related to the effects on the placenta from SARS-CoV-2. Conclusion(s): As more information comes to light about the effects of SARS-CoV-2 on the placenta, it is important to consider a maternal SARS-CoV-2 infection during pregnancy as a cause of HIE in a newborn.
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Background: The placenta functions to provide fetal nutrients, adapt its nutrient supply to match extraction, and mount key inflammatory responses. Placental pathology exams can offer insights and explain long- and short-term adverse events for both birther and fetus. The combination of recent indication developments (i.e. COVID-19) and varying education around pathology reports is resulting in increased pathology workload, result turnaround times, and timing of family consults. For placental pathology to guide clinical decision-making, order indications must be informative to decrease pathologist workloads reviewing electronic record, and timely reports must be returned. The objective of the study is to identify gaps in the workflow of placental pathology processing to facilitate informative orders, improve interdepartmental communication, and educate for better clinical counseling. Method(s): Quality improvement (QI) fishbone diagrams outlined problems and solutions for timely pathology report turnarounds. 3 mixed-methods surveys were sent to UW pathology and general obstetrics (Ob) residents, maternalfetal medicine (MFM) and neonatal intensive care (NICU) fellows, and attending Ob and MFM providers to identify knowledge gaps, preferred educational tools, and free text thoughts about interdepartmental communication around placental pathology. Rates were compared by Chi2, Likert scale data were compared by Mann-Whitney. Result(s): Survey response rates from pathology trainees, combined Ob, MFM, and NICU trainees, and the Ob attendings were 23.8%, 27.2%, and 50%, respectively. Sufficiency of placental education for Ob and MFM trainees and attendings was rated 1.95/10 (n=21) and 5.5/10 (n=8), respectively. Delivery attending Ob/MFM providers rated their confidence family counseling as 4.86/10 (n=14), with MFM providers' expressed rating higher (7/10, n=5) than Ob (3.67/10, n=9). Overall, interdepartmental communication surrounding placentas was rated an average of 1.9/10 (n=30). 4 Ob residents reported receiving no training on the topic. 3 Ob providers expressed that reports often provided no clinically relevant data. Conclusion(s): Utilizing survey responses, 4 interventions were chosen to improve education and communication, including the use of a .placentalpath SmartPhrase, a teaching tool, updated indication guidelines, and regular joint interdisciplinary perinatal case conferences on relevant topics. Future directions include implementing, following, and assessing the effectiveness of these instruments.
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Background: The emergence of coronavirus disease 19 (COVID-19) as a novel zoonotic disease has been of international concern, with recent studies highlighting the potential association of COVID-19 with placental vascular dysfunction.1,2 Because the increased incidence of histopathological lesions could imply an aetiologic relationship with SARS-CoV-2 infection, this study aims to audit the spectrum of subacute placental disease occurring in COVID-19 positive mothers. Method(s): Histopathological reports were obtained from Liverpool Hospital from 18 March 2020 to 18 March 2022 and subjected to retrospective histopathological report audit. Three hundred and five placentas from mothers with history of COVID-19 infection during pregnancy were compared with 305 randomly selected controls with no reported COVID-19 infection. Information obtained included maternal age, fetal gestation at delivery, macroscopic measurements and 12 histopathological variables. Missing data was imputed using a random forest algorithm, with downstream multivariate statistical analysis. Validation of findings was performed via non-linear principal component analysis (NLPCA). Result(s): A significant increase in mean placental weight was observed in mothers with a history of COVID-19 (COVID-19 cohort 480g, control cohort 423g, p < 0.0001). Median gestation was significantly increased within the COVID-19 cohort at 38.2 weeks compared to 36.5 weeks in controls (p <0.0001). Surprisingly, there was no increase in histopathological lesions within the COVID-19 cohort. Similar findings were confirmed with NLPCA. These findings highlight the possible resistance of the placental disc to COVID-19 infection and the utility of utilising imputation and NLPCA in the study of potential new pathological entities. References 1. Wong YP, Khong TY, Tan GC. The Effects of COVID-19 on placenta and pregnancy: what do we know so far? Diagnostics 2021;11: 94. 2. Boyraz B, James K, Hornick J, et al. Placental pathology from COVID-19 recovered (nonacute) patients. Human Pathology 2022;125: 18-22.
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Objective: Severe Maternal Morbidity (SMM) can be considered a marker of both maternity care and maternal mortality. The aim of this study was to review SMM in 2021 within the National Maternity Hospital (NMH), a tertiary level unit in Dublin, Ireland, with more than 9,000 births per year. Design: The study was a retrospective cohort study of women who experienced SMM in the NMH, Dublin in 2021. Methods: SMM was defined using the criteria established by the National Perinatal Epidemiology Centre (NPEC) in University College Cork. There are 17 reportable morbidities including Major Obstetric Haemorrhage (MOH), Eclampsia, Peripartum Hysterectomy, Anaesthetic complications etc. Data was prospectively recorded from a variety of sources including HDU, Pathology, Placenta Accreta Team, Maternal Medicine Team, Microbiology, Haematology, Anaesthesiology, Labour Ward. Data was included from Jan 1st 2021 to December 31st of the same year. Results: Using the NPEC criteria, 41 women experience at least one SMM during this time, of which four had more than one SMM. As with previous audits and in parallel with National and International data, the most common SMM was MOH with 18 cases. Five women underwent a Peripartum Hysterectomy. Seven women had Renal/Liver Dysfunction, mostly as a result of Pre-eclampsia. Of note, given the context of the COVID pandemic, there were no patients with septic shock due to a COVID infection. There was one late maternal death due to metastatic carcinoma diagnosed during pregnancy. Conclusion: This study highlights the importance of ongoing training for new and established staff members in obstetric emergencies, such as MOH. It also demonstrates importance of audit in the clinical setting, where ongoing reviews highlight issues of importance.
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Objective: To describe histopathologic findings in the placentas in women with coronavirus disease 2019 (COVID-19) during pregnancy. Methods: In a cross-sectional study, 38 pregnant women with COVID-19 and undergoing delivery between March 2020 and January 2022, were included. The patients had positive polymerase chain reaction (PCR) test for SARS-CoV-2 infection and the placentas after delivery were sent for histopathologic evaluation based on the Amsterdam Placental Workshop Group Consensus Statement and assessed by two pathologists. Results: Our results showed that maternal vascular malperfusion was the most common and was present in 17 cases (44.7%). These features included accelerated villous maturation (36.8%) distal villous hypoplasia (5.3%), placental infarction (5.3%) and intervillous fibrin deposition (10.5%). Other pathologic findings included focal calcification (10.5%), intravillous congestion and hemorrhage (10.5%), sub-chorionic hemorrhage (5.3%), acute villitis, chronic histiocytic intervillositis and delayed villous maturation each in one case (2.6%). Twelve out of 38 cases showed no significant pathologic changes. Fetal outcomes included neonatal intensive care unit admission rate of 13.2%, dyspnea 31.6%, newborn's anosmia 7.9%, intrauterine fetal demise 2.6%, asphyxia 2.6% and neonate COVID infection 5.3%. Conclusions: Microvasculopathy, as a sign of maternal vascular malperfusion, is a common finding in placentas from SARS-CoV-2 positive pregnant women in the present study. Further studies with larger sample sizes and comparative studies between COVID-19 positive and negative, as well as information from patient follow-up are suggested.
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Background: Although there are many studies examining the clinical outcomes of women and their infants diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, during pregnancy, the reasons causing the possible adverse outcomes remain unclear1. This study examines placental pathology from women who contracted COVID-19 during pregnancy at this university hospital institution. Design: This study was centered around all 19 placenta specimens from patients infected with COVID-19 at this university hospital. The American College of Obstetricians and Gynecologists (ACOG) allow for the judgement of the Obstetrics physician to be the predominant factor in the decision of sending the placenta specimen for pathology evaluation. Therefore ACOG and CRICO (a risk retention group for medical practitioners) work in conjunction to recommend that placentas be sent for pathology evaluation when clinically indicated. All 19 placenta specimens that were submitted in this study met at least one of these recommendations and therefore 19 age matched controls without COVID-19 infection were reviewed in order to outline any significant clinical trends. The age matched controls were selected within the same time frame as the COVID-19 specimens, which was June 2020 to August 2021. Results: The interval of initial COVID-19 diagnosis and time of placenta evaluation was documented in each case, with the median time interval being 2 days (minimum 1day to maximum 91 days). The gestational age for each patient was calculated, and the average gestational age was a full term pregnancy of 37.2 weeks. 90% of the patients were identified to be of Hispanic ethnicity and heritage, while the other two patients were of Caucasian descent. 63% of the placental weights from the COVID specimens were 25th percentile or lower, whereas only 21% of the age matched controls were 25th percentile or lower. 63% of the cases were recognized to contain histopathological abnormalities, 10.5% in aged matched controls. 4 cases were found to have intra-placental infarction (figure 1), 2 cases were identified to have chorangiosis, 1 case of villous ischemic change, 1 case of decidual laminar necrosis, 1 case of meconium, and 2 cases of acute chorioamnionitis. Conclusions: In this study on average the placenta weight was identified to be lower than age matched controls and placental abnormalities were identified more often in patients infected with COVID 19 (63% vs. 10.5%). (Table Presented).
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Case Report Disseminated Herpes Simplex Virus (HSV) is a feared neonatal infection typically presenting after the first week of life with sepsis-like features and encephalopathy. Congenitally acquired HSV infection represents a rare, serious variety of HSV in the neonatal period, providing a unique diagnostic challenge with significant morbidity and mortality. A female infant was delivered at 29.2 weeks gestational age via cesarean section in the setting of non-reassuring fetal heart tracings, maternal preeclampsia, gestational diabetes, and Sars- COV2 infection. Physical exam at 1 hour of life demonstrated erosive lesions of the knee, foot, and cheek. Dermatology was consulted and favored infectious source of lesions, so a sepsis evaluation including HSV, VZV, and CMV studies was performed and ampicillin, gentamicin, acyclovir, and amphotericin B were started. Given high concern for HSV vs. varicella, ophthalmology was consulted, finding bilateral, likely viral, retinitis. Laboratory evaluation revealed transaminitis, thrombocytosis, and CSF pleocytosis with elevated protein. HSV PCR was positive in blood, CSF, and cutaneous lesion, as well as HSV2 positive on surface culture, yielding the diagnosis of congenital disseminated HSV with meningoencephalitis. The remainder of infectious studies were negative. There was no known maternal HSV history, although placental pathology revealed positive immunohistochemical staining for HSV 1/2 in addition to Sars-COV2. Patient's serial CSF and blood HSV remained positive despite treatment with acyclovir. Serial HUS showed initially normal findings that progressively worsened to feature bihemispheric cystic encephalomalacia, periventricular leukomalacia with ex vacuo dilation of lateral and third ventricles. She developed central diabetes insipidus and was started on desmopressin. Ocular involvement subsequently included retinal necrosis and diffuse retinal hemorrhage. She developed severe myoclonic jerks in the absence of electrographic correlate on EEG. Levetiracetam and phenobarbital alleviated jerks, although she developed progressive hypotonia as neurologic status continued to deteriorate. Considering persistently positive HSV studies, foscarnet was added to acyclovir. However, at 3 weeks of life, she was intubated for apnea and respiratory failure, and given clinical trajectory and devastating prognosis, mother asked to compassionately withdraw support and allow natural death on day of life 25. This case of congenital, disseminated HSV is particularly unique in that it occurred in a premature infant of 29 weeks gestation and had significantly elevated copy numbers in the blood and CSF as well as skin lesions, indicating likely longstanding infection at the time of delivery. Additionally, it is unknown how concurrent placental viral infections with SARSCoV2 may have contributed to this patient's course, or if the recent maternal SARS-CoV2 infection may triggered HSV reactivation and subsequent congenital HSV.
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The proceedings contain 43 papers. The topics discussed include: recurrence risk of villitis of unknown etiology: analysis of a large retrospective cohort study and systematic review;prevalence of chronic histiocytic intervillositis before and after the COVID-19 pandemic;examining the impact of villitis of unknown etiology histopathological lesion and adverse clinical neonatal outcomes in an eastern ontario maternity population;SARS-CoV-2 infection of the placenta should not be called “SARS-CoV-2 Placentitis”, a term that is misleading, not supported by the literature, and should be abandoned: a review of the literature of chronic histiocytic intervillositis;placental histopathology associated with SARS-CoV-2 infection in pregnancy: preliminary data from a prospective cohort study in Ontario, Canada;intervillositis in placentas from gestations complicated by maternal SARS-CoV-2 infection: fetal and neonatal outcomes;recurrence of placental lesions in a pathology sample;and impact of co-existing placental pathologies in pregnancies complicated by placental abruption and acute neonatal outcomes.
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Objective: Studies have shown that the antibodies developed in pregnant mothers who have been infected with severe acute respiratory syndrome coronavirus (SARS-COV-2) are able to cross the placenta;though, there is a decreased efficiency ratio of cord to maternal anti-receptor-binding domain IgG titers. Viral mediated placental injury may explain this finding. The objective of this study is to examine the relationship between transplacental antibody transfer and abnormal placental pathology in pregnant patients following infection with SARS-COV-2. Study Design: Pregnant patients with COVID-19 delivering at Grady Memorial Hospital were identified and enrolled into a prospective cohort study. Maternal and cord blood samples were collected at the time of delivery, and concentrations of anti- SARS-COV-2 IgG spike protein quantified using an enzyme-linked immunosorbent assay (ELISA). Placentas were sent for pathologic examination at the discretion of the obstetric provider and examined by trained pathologists for size, presence of infarcts, and other histologic findings. Results: A total of 12 women were included in the study. Demographic characteristics and clinical outcomes are reported in Table 1. There was no statistically significant difference in the mean transplacental antibody ratio for patients with and without placental infarcts, with the mean (SD) maternal:cord antibody IgG ratio for patients with infarcts at 0.67 (0.47) and without was 0.73 (0.35) (p=0.81). Maternal hypertensive disorder and the presence of symptoms at time of infection were not associated with infarct in this small sample. Conclusion: Results demonstrate that in this limited sample, placental infarcts were not associated with difference in transplacental antibody transfer. Further studies are needed to understand mechanisms underlying transplacental antibody transfer. [Formula presented] [Formula presented]